Mathematics » Evolution Fred HoyleCopyihe © 198,19 Fed Hoyle Allsighs served No pr of his puieaion ay be ‘robced or ated i any fae oy an mean lest ‘Sneha cating emcaprng reconing ce Bae inrmaron stg and recralpem, ithout pioreiten Fermison of he Pulse rial aval in sunscreen a Matas of Een Sleton Rblcatin onthe Connie Ong of LAG No.1 1987 by Uniaaty College Cari Press Unie Kinglom Fst American ein es hy the autho an pub in 1999 by ‘ew Eateries LLC. {508 Unie Aten, Suite 226.8 Memphis ennene 38104731 Phones (901) 726-1111: ax (901) 726-0120, Ea tiycooarapermin.one Litray of Congres Catalopngin-Pubition Data Hole, Fed atheraties of ekon fy Fro Hoyle Iie ein he USA pc Li! isan a665934.0.5 so.n560 or Pater, Big Kye EltgrarChek Dane Nes Fabs Cone: Robbin Pret, RBene&Company (Coe an Inter Dep Hastings Doig Flamingo on ss nd char sie apr: rd Hoge Publi inthe Unite States of America 10987654321 Inemory of George CasonTable « Conte © Farenrs wae © Prtace © Inrotveton 1. Selection andthe Mu nee Prien 2 Gal vison ané rossaer 4, eal Masel wit Crossover 4 Th Solution af the Sine Gone Probie by a Paral terol Euan 5. Salta! Cnseqenes of ‘eleterius Nuatin Pressure 1 How Far Dos th Nen-arinian Theory Work? 1, The Geetio Gost of Evolution Protein Pyogenies—Moreasins 8. Summary and Cecio 9 a@eaaeoreword Ave ie Hoye wrote Maton of Fs 1987, only hands csi cope fhe handiten manag were poet Few who woul be ns iis contents ever aw bean about the mans. happened to ele ito Hoyle longtime collate, Chanda Wicknmasnghe, who gre me xcopy when vied him in Caf, Wales in 1995. Les ey impeeed with he enetatng ait contin sd mone bythe sory bind i dont George Cason,Speeeeteerta creme “The following yar I met Sic Fred Hoye a the Institue for Assonomny In Cambridge, England, which Hoyle had founded in 1967 and head or sx yas. There, in the former residence of Sie Arthur Eington he spoke With me at length about his wok n biology. [ame away with ven greater lmiaton for bis integrity and his contebutions to scence and with senuine affection for him It seemed 2 tragedy dha his Mahemaice of eoluion had not been typect and widely disribured, Concern that this work might be lst toa larger uence, Fakes him if could publ i, nd Ihe red, In 1997, he wrote anew pefce and overs the mince evsons requited (Otho scientiats,sch as). B.S, Haldane, R.A. Fisher, Sewall Wright and Moto Kimura, have worked extensively on this subject, and Hogle eal to any of them in mathematical sil. Being iconaeistie, he isnot scourge when his anal lea oa rel diferent that reached by his predecesson. And Profesor Hoye tell story well Even de complex mathematics in some chapter are arate with sraighrorwar, singe and engaging text. This sa book that many readers —not jst done who ate ‘mathematically sopisicated—can easly benef from and enjoy But there ‘seven more hereof value fr geneticists, mathematician, and scientists in any fed who are interested in evolution. Inf, dhe greatest purpose thie ook could serve would eto rekindle within mainstream cence broad it and serious consteration ofthe ies i aes “This isthe fist hook I have published and took mone ime an foe ‘than [expected Bu ere i Fly. 1am gratfil to Meg Johasoa, who rater’ Hoyle handweting and keyed the text and equations into the ‘computer accurately, and in record tine. Iam extremely gratefil to Diane NNesn, who also mastered Dr Hoses handwriting, etd the typescript communicated with Sir Fred, transcribed his revisions, slved vexing software confles, helped me fn other resources, and encouraged thet sick with ig am grate to Robbin Brent, who made the design and rodutio ofthe bok a smooth and enjoyable proces. always appreciate the super and steal aasitance of my adminisraton, Babara Masco, svthout whom | would be ineapaciatel. And my deepest thanks no my wife Ellen, who provided loving and exenil supe, instead of reoramending pevcholopicl counseling, sir Ulf perctly good jo to pus science fulltime, Finally 1am grateful to Sir Feed Hoyle for doing scence so tle and courageously. Brig Kye 25 May 199Preface There is fair flow of anti-Darwinian books shemale Attn oneconin kd arpmens agit tho he modes arhonseo oe teal Te moive he et doo se cnc of rol, ned wecoge sem 2 sig feneen nn legs 0 tom whos og othe ee ‘askt. Casing them pethaps to wonder ifsight not he the same with this book. Well, i sn: Admittedly was Trough upin the Bec state school system ex 1925, which was certainly religiously oriented to an extent Americans will hardy credit In fac, 1 ‘cored wellin religious examinations en acount ofan ety felt for being able to commit long pasages fom the Ble r memory. Ad toes chat | ‘vs one of he members four eel church choi. (Our chore want scien grand to have is own vice. But the locese sgn ws a crite who would on et Sundays climb the il fon the neat town to our ville. Rr visitysak if not fr his own, he would ‘other erates to sand i for hi every two or thre weeks, and sometimes ‘lay preacher. We boys liked the ay preaches, because once they oe fy stated they would mostly foam along with le rey for vocabulary ey ‘ax. One diya sal hice san in boos clumped upthe wooden tps to the pulpit. Afera minute ors taken in etn hil, aden ore ‘out our innocent-looking congregation: "The numberof the beast Fei the number ofa man: and his number is sx hundred three scoe an i.” Tedd ake lng for me to workout tara unde thee score and sc was 666, numbers being meting with which I epaded myself as being fay expert Dd this mean the number of men in the world was claimed be 666 Or did de mean whar ic aud Leeraly—chat 666 was nuber arzached toa ptciclar mun in che fasion of a convit? Ether way [ele lind dube chat eis particular preacher was seriously dein the bead. When asked our teacher of religion a school abou it Iwas told thar dhe tex was fiom the Book of Revelation, which pethaps should't be taken too seriou. Maybe not, but forme it wasa wave of incoming rie licking away seasand ce ‘The sand castle was entirely washed away all in a moment about two years Inter. This time there woul he no deube about the source othe top. The sources were the sacred gospels of Matthew, Mark, Luke, and John and ‘thetic was central to Christian faith the Resumection. [had the thought ‘one day lockup and compare wht the four septs had os ahout events ‘ofa the tomb of Chri, explicitly with reference to these questions: Who mong Chie’ frend, elativs, and dips int came tthe tomb! What ‘wa the physical condition of the tomb? and How many angels wee present ‘there? To this pone {had been willing to accept such superatural gents angels Indeed, angel seemed to me so remarkable that i mattered quite a Toe whether thee wa one of them, tho of them, or three of them in i coc What fn] wa hat 04 men Math Mabe ae raped pec fs gle ssn nigel mantis ‘onde sow nna eon insy tte wile wut ben ae torepr comet Tit toc pued fin afm ie wan te avo fom fin chetbel te, Ont fy hea etch na week Ot of flit tre Chon wlon in rot mac Ceo of ay be ay amet lig in le mow te than th Sie the, he eat as ann ont ou, avoy fe any btm ig whi en Rave nen dow ce eet one ie “The cntcsn of the Darwinian theory given a dis book ates scihoerry omy ble hac the theory wong, nd cat coined Therence oan impediment to dcovering the comet every Sheu To the extent ha one deft y scoreline fen conectng at wrong one hac coy 0 opponents "To deny the paleotlogcal evidence of evn, andi paar tna plc tn son pr wth dying tae we Res doa nthe Darin theory whl me ows dw al ight Bows ine ha te camel to be unimly gd, «grad er Peg oe that em Sori a «sea angle fem ee 9 these, Because He entice fow ver ts of neve aoe, hey soni hry dows Il hey some dle “The River What in ts ow ove leone rocks above the wb of Taken pc v2 sis foal fl over Feds fot eof het inter of ite change spec by all mys The name prc {lon has ben geno eshaton poet loa this at Suercan sls go dob fare pecaculyay wththe Naga River Between ak and Lake On. it nope evens onsuchascale than erections of his ek haves he ame ene Rom “The hig phys sor oscuing nen Yeas sly ees snus al he oe pt oper Ath assim ned Ye Diwch or more than al the re. And, perhaps, even che biggest ina Shonda Something of the mee so Soest happen with evel, The fine -ning genes poe sll changes The ation of rurely nese pape ne ees new ene ods se Shanges gre eta the gene complet of an aed existing ‘nie ofeee eer [A decade ago I chought new genes were aeuied y an oni fom the extemal envionment, just a bacterium sequies «new gene by picking ‘paplasmd,excepe that unlike she bacterial cae its extemal envionment was taken 10 he extemal to the Eat At squsition, 2 new gene wat supped t go it nt the store of redundant DNA a proces contig ntl a considetable number hal been aed, when, in agent oem, cell roa become shuld by aval frm of interference fom curd. Most such shufings would came to had end. Buy occasionally a stston both new and workable in a new aiche i the temestril envionment wat considered oar, sting evolution offen new path eda, however, would maf this plete somewhat to te view cha all genes in present-day oganis were here already n the metazoan that ‘invade che Eanh 570 millon years goat the beginning ofthe Cambrian Ex, making the subsequenr story of tees evlition ina one in which gents Fave ben called into operation as ecologecontions permite them tbe ‘0, For example, ir would have been pointes ell in a genetic system leading 1m the appearance of flowering plants before che means of sicesul pollisacion existed. The inate interweaving of many organist had to proceed in concert with each in a pater that has own every more complex wih the pasage of tine. The fit metazoan were relatively simple forms thar could exist by themselves on an undeveloped Earch, bur they already posse the genes neces fo thee subsequent development. ‘This & a more eficent way of seeding a planct with life than a sentially random proces af aeuiing genes would be fie exits in the universe om a vey and seale, we woul he Hcy to have received on the run oaly afer a great del of evolution had steady taken place In which cose, the mosteficient procakires would have Become eablished alzcady by 510 mllon yeas ago. (Genes that are lly unexpresed aecumulae eros by neural dei | arate of “10 eos per gene per generation. Afer a geological interval of “10 years which implies 10 generations, there would thas be “100 eros mong 1000 hase pairs foreach gene chat was being held in storage agin furureevolaton, reiting na serious asf ficiency bythe ime such sore genes come to be atvated, Bur roving mating of population rumber N of the fase organiams were lange cnoush, efficiency woul! icky be recovered, By the asgumentsof Chapter 4, the probably fever becoming fied by random drift would be IN. Hence ws long as Ns lage compared wah he outer of generations ver which df ccm no mevcale “image oc Wheras ant eth othe pops weld ve a purer hc pur weng on the DNA of gene unpeeeed yeaa ‘Een 100 ion yea nines of the populton oul il ave STaghe Then enc the one crate ela in weal ees wih Cromer renve tees uty tulle, alent ane Gant peel nelle Tea doco thi the ist xno 570 millon yea p> weal have ola eet pen ue ot sce Chater a tepoducio by putes woul reba Bence in ole 0 Che that N Kecoes ge eon he wo sex 1 fd eh thet Steely ogo tt oe can ovine dated Keyed 300 Ilona aga tho equ ce oe well me —Fred Hine BournemouthIntroduction ‘Tris esay has been a long time in the maki My eats research work wa in tian fom schoo, in which [wis cea enough to tle down the time T pene mew up in clasooms to something ik forty percent of what was suppose tobe hereon the aes of five and nine. Iwas an esental par of my tem that nether the school nor my parents shold know where Iwas ding the daytimesimply dlappeared, lke H.C. Wel’ Invisible Man, excepe that beng only small boy, ws easier for me.I sappeared into the woods andl, with plenty of tine to watch binds building thei est, to watch che an ling and the seams rising. So it came about that I knew the names of every lower and tee an he whereabous of every animal in mv home dre. All tt homespun knowledge was wiped clean from my bin by the age ‘of eightcen,bocause by then I had become convinced that biology was 9 oubfl subject. The touble was that ia reading widely during my eat teens Ian into the Darwinian theory fr a lie while with isons and ‘hen with les respect than as with bated Breath were wont to show. The ‘theory seemed to me tor ike thi Iamong the varieties of species here sone that survives beter in the envionment than the others, then the vlety that survives Fests the one tha os survives TET had known the woed taxoogy I would have called this tautology. People with sil mre had breath, alld ie matt selston. made them angry, jut as do today, by saying tial nosing at al. You could select potatoes as much as you pleated hut you would never make them ito & rbbit. Norby slecring ak tree could you make them int colonies of bats nu hose who chought hey could my opinion were bts inthe belt. Ths ‘made thet angry to: Ode fon the kno tld me that selection didn't ‘operate ro make complicated things of compli hing nly to make comple things out of simple one. I couldn understand how anything of the soe could be gue, Bocas unlikely ati was fe would surely be es ical to make arabs out ofa potato than to make arabe out f sade, snhich s what people sail had happened, people with ine afer line of lester sier their names who should have kro what hey were talking about, but obvi did ‘The Mathematical Tapes at Cambridge interened to occupy ny though andi was no unt began reser ofl in 1936 that blog reared is head gun. This was case I beat fend with George Cason who was thon jus completing his PhD. in bana 1938-39 | shared “is” wth Gsore, 9 biological opis tually occupied afr ction of cue ‘comeation. Carson was among a minciy of blogs who have auspected something be amis with the Darwinian theory His potion was sina to thar of Aled Russel Walle in che ater’ later yan. Something wo ht about the thsrythere were to many examples of niche matching between speci charactetstis of ucts and te precise details of the environment forthe thoor not tse comernsome dere but not wholly comes. Geom tvs prety well unique in tliving that whar was msing ould be discovered Ir mathematics He never ceased, hot in our stent ays an in ater ie styng to nvege me inc. serous vestigation of elution ard when kid otis tothe Fie, George was forever boring ay athens books. He ‘foul si wth them of an evening with the conviction that somewhere he Mould finde chu he was looking for Nether spotted this lu, namely thac terest logy io a sed system. Te waeand sill very hard to arrive at this concept fom inside biology The trouble Tay in at emit cul strgple which fad developed from 1860 onvard between biologists on the one hand and the Supporters of old licfson the cer The old livers said that rabbits had een created by God wing methods too wonder for us to comprehen “Thennew believer si that its ha ben crated rm shu by methods ton eomplex for us to ieuate and by methods likely enough involving impel happenings. Impwotable happeniegseplaced miracles and shige replied God, wth Plivers both old anid new seeking to over up thet fanerance in clouds of won but diferent words. Ie was over the words hit sons raged, pasion which coninie to ramble on in the moe work sons thc one an ead abou with ilarioussaifiction in the columns of the weekly science mayssine Nonee au Isten co in baso profunde pro- ‘ouncemens fom leame sent socetis, Because the old believers sid that Gad came out ofthe sky, thereby connecting che Ea with evens fuse the new believer were obliged wo sy the oppose and ro do 0,28 fvajs, with intense conviction. Although che new Believers had not a picle of evidence to support their aemensson the mates, they sete thac the rabbitproducing sadge (ied soup to make it sound more palatable) was terstlly cate au cae alchemical and biochemical ttansmogrifications of dhe slndge were tenestaly inspired, Becase there ‘was not a particle of evidence t support this view, new believers hal 10 wallow it as an article of fit, otherwise they couk! not pass cheir ‘raminations or sceurea job ot avoid the ride oftheir colleagues. So it ame aout frm 1860 onwatd that new believers became ina sense mentally foc more precy either you Feeame mensally lor you guited the otesubject of biology, as [hal done in my early eee. The trouble fr young ologbts was that, with everyone sound them le bose impossible for them to think they were well ules they were Ul which agai station yea can ead all shut in the columns of None eventually retumed willy-nilly to biology in the flowing way. My O, with then a favourable propery that rises to unity with ll mbes of the population coming toposes tin time spn of ~In ss ners. Forcxample if x= 10* ands = 001, the time spon woukd be about 1400 generations, small camgared to the intervals solved in biological evolution, And if <0 the solution des sway in atime span of order Is iznertions chereby implying that As unfavourable it wll be quickly sejere. Tam convinced it is this almost evil sinlicty chat explains why the Darwinian theory ss widely accepced, why thas penetrated through the elucational sytem completly. Asan sade ext puts "The tery a ewostep proces. Fit variation muir exist ina population, Second, the fiaest members ofthe population havea elective advantage and are mone Tikely to uansnut their genes to the next generation te eee But wha individuals with good gene A cary aba gene Bhavingthe larger vale of Doesthe bd gene not ery the ood one downto dst? ‘What the situation that bad mation mest enormously exceed good ones innumbe! Lets take firs lok atthe comparative aes at which goed sad Tha mutations are likely ose. Most mutations conse of base pir being ‘hanged during the copying of DNA. Because amino acids are coded for by Triplets of base pais with 64 diferent wplts avaiable for only 20 ino cds the gentle code as an approximately 3 to I redundancy in i This fan Fe taken cate of to saicient accuracy her by etn che shir member ‘oF cach triplet be considered redundant. fwe set 3+ 10° a the chance of {ny persicae pir being mscopied, che chance of any amino acd being Charged nthe protein to which a gene gives expression s~6 + 10%. Thus a frei with about 160 amino ack in its chain would havea chance of 1 fin alin of bing miscopied—thae i iff one amino acd in its chain Fring changed ina random way "A. single set_of manimalian chromosomes bas approximately 53+ 10 base pits of which pehaps 95 percent pay active ole, ment of the DNA ting aparently sonfunctional wih respect vo gene procs “Taking ~10® ae pis as che total number which are geneially relevant, ‘the mutation rate per sage chromosome wet is ~3 + 10% + 10° = 03 per generation, Fortwo chromsonne sets the rt sO per generations ha ‘considerable fraction of indie bor in every generation exhibit ve few mutation, the great majority Bing harmifel in some degree. The ‘penta peoblem fo the Darwinian dheoy in its wentieth-centery form i thom cope with cis continuing lod of averse mutations. a far crise from the tte problem of only the singe muration i (11). Sopposing 3 favourable mutation to occur among the avalanche of unfavourable ones, how isthe favourable mutate o advance aginst the downward pres of theothert “Merely scking to emove Kad mutates by ineerse mutations which rerum genes back to thei orginal forms ia uscles enterprise Suppose that Compared to an exginal pine genetic sucture a species has been fenetated by 3 hundred deleterious entations each with 5 = -001, 90 hat the lowe of competitive fines compared 0 the exginal station (1-001)! ze! Forasingle averse mutation the chance of ing st sight Tyan inverse mutation ~10” per generation. Hence the eoretin rate foe 100 adverse mutations & ~100 + 10% = 107 per chromosome set per fesenercion, Compared mo che ongoing rate of 0.3 adverse mutations pet hromesome set per generation the eoeston ite i extretely stall the flood of deleerious mutations tobe held in check, tial election mse ‘therefore do che ob, no inverse mutations ‘The reason why most mutations most be bal sof coun that andor ‘changes made to any complex sructre lead to many more down ep In the operating eficioncy ofthe stactre dha to uprand steps. How the ‘occasional lucky improvement iso lad to psitive evolution pale that yas sturbed many mathematicians. In a bulking model oF binary isin model in both of which progeny inhest she genetic strc of single parent the situation appears unpromising. Rae favourable mations such medcl cannot fre themselves fom the more frequent unfavourable ‘ones, Hecause an ofping to whom tare favourable mutation occurs ineviabiy sided with all the unfivourale mutations which have afc itsporecal line To have any hope of succes the neo-Darwinan dheory must eerie appeal to a reproductive model quite diferent fom the model monty adopted by single-eled organisms This already an amense clin dewen fom what sully claimed forthe theory Gone sts“ stats. Only ifamodel can be found that contrive to uncouple the selective properties cf ‘one gene fom another, permitting the occasional good mutation 1 survive and prosper ina sex of had mutations, can evolution be made ro work a all How exquisitely complex the movil needs to be ro achieve such a remarkable result will be disused in the next chapter Then the ‘mathematical properties of the complex model wil be investiga up eo the end of Chapter 5. Thera, in Chapter 6, we shall Ee in a position to discuss che extent to which the neo Darwinian theory can be essidred to ‘work an the extent to whic ean. To anticipate the events outcome ie wil be found thas, subject t0 the choice of @ highly sopintcated reproductive model she theory work a the level of ares ad pees, jst 25 1c was found empirically o do by bilogts from the ml-nneteenth century onward: But the theory doesnot work at broader eaxonoan levels itcannet explain the major steps in evolution. For them, something nat conserd in the Darwinian theory is sential “Tobin the present consideration of asngepareat-o-fpring model, let us note that equation (11) was noe normalised propesy tb mainain 3 stable population fram generation to generation. Suppose the average -f. number of effpring suviving fo reprodoctive age from an individual pressing gene pe A ie (1+ =), compare to fr the ofpring fom an erage intvidil of gene spe a Then for a sable population to be tmainained (3) must be function of the faction xof the population with A thats given by a [eseet-s] a “Ting the generation interval a the uni of the ime t differential cquation for) ca be obained fom x (+l) = a(l+s)x() ct) Weiting x (¢-+1) = (9) + dian sing (23), we have for << 1 Hel) say, as) @ tse which is already ore complicate than (11). For the Boundary contin P= apce Late tthe slusion of (15) roche fist ne ins is given by sex) 5 aa = Tergfesn(s)—l] © + ews) ‘Unlike the slucon of (11) foes» 0, x does not increase ro amity =f] slut ony oJ Indes, according t (1.6) for > 0, x doesnot increase atcly to unity st any finite time, Property A doesnot completly “Ha elf in the species in any nite numberof generations. A resid of invidals remain with the disadvantageous peoperty a. This is on the spposition thar each individual produces the average quota of surviving ‘pring forthe clan to which it Belongs 01+ 9) oping the gene type Is. afthe tye isa. In practice, however the numberof surviving offpring provdced by any individ has an element of chance int thats quite apa fiom the genetic situation. Because i is imposible co recover from, ‘etncton, chance operates a8 one-way stret. On occasion, individual akthe woe pnetc type may be helped by luck, but such temporary ood force sof permanent alvancage case an ierese i the number of individhals of type 2 omly gives natural selection tore scupe to oper ‘When, however, kad ick cs aginst individuals of reo inally casing hele number to drop to 210) i extinct and the game is over Tas ‘combination of genetic pressure with chance enveonmental cantons ‘ypial of many stations in biology. Whenever genetic pret forces down the numberof indivi posing a prsicula propery below a certain level, itis then an adverse envionment ctustion that delves the ial How eo survival ‘According tothe ahove dicusion of mutation rats, the number of potential kad mutations i of erder 10%, the numberof sensitive tae prs Writer for this number, and for split take al dleteroas mations to have the sme rere election factors 0. Also take the probably of ech tad mutation appearing to be the sume, A 1, where a 03 isthe tol probability per generation of ane ofthe tains appearing —that 2 the average number of bad new mutations appearing each eigrng ie hoen. Fuctuntions given by the Poison dstribution wil evidently occur fons ‘ofpring co ofpring with A exp 2 tue probably that an oping i born with defects: Homever, fr. aprecahly ls than unity, che Poison distribution is dominated by k= O and k = 1, with robes I~ and, respectively tothe ist onrin 2 Only these two posites are considered in the following equtions ‘Write 1{0 = 0, 1,2, «for dhe ection af the population with no eft, with one defect, two delet... and write a (1) forthe number of surviving pring proncd by an inva with r delat. This in @ ‘model whee from generation to generation parents dle and are replaced by thei ofpring the surviving ofpring” being those who themselves corn parents inthe sueceeding generation, From the definition ofthe eto art: an an frm the contion thatthe population remain sable rom generation to generation, then Me aX e-W yet ws) “The fllowing equation relate to factions fom generation to generation wich frctions in the + penerationon the ll and action in the «gene tion cn the ight seler={all-Aroh, + os) yer=(a(l-p)- aly tanh (1.10) vaeena{ a[(-WYC-ay,+ 0-H)" 4] f ‘oan “aking the fess 0 vary showy om genet gener, rteeD= me Se) PO Gay ence he dni quo fr) ae Boefa(i-A)-i] + a) a aiyy+la(t-a)(t-)-I], ay % ADAP ™y,¢ [att-allt-iel =I, (us)which ae tobe solved subject to the Boundary conditions PreL2ou attime ¢ (116) oly Remembering cae the normalisation Fat eri funtion of time aconding 10 (1.8), we evenly have ast of nonlinear equations fr detenining the ow ofthe deleterious mutations, see that finite, although may became nonser at moderate or high vals of. Tniially = 1, so thatthe coefcent of 3s on the right-hand side of (1.13) is ac fre: Hence declines initially exp Ai, wich for b= 0.3 isa seep fill needing any afew generations forthe efet to show in a -somserbl fll avay of Eston (1.14 gives iii build of that ‘soften encountered in low robles of thin Kind. Because of the yy er on the righthand side of (1.14), 9 at fin incre but then checked by ‘the -fo(L ~29(1—Inl) 1 3. cen. Ths rss a in, then 3, atin a ‘maximum asthe wo cams on the right-hand side of (1-14) cancel each othe a herenter, falls away toa lower vale. As time go 9 ‘how a similar Behavior Aine plot ory would show a curve that declines szeply at fst and then levels oto some ultimate valu, Ss, we ie plots foro re curves that He tall fm eo to maxima al hen fall away and level ou a ulimate values, 5,5, say. Our problem tt ‘aeulte chese ultimate values araine nie sales “1 generations. ‘As the ultimate valus 5 5), ate stained, the ight hand sides of scuations (1.13) to (1.15) go to seo. The inverse procedure of sting the right-hand sides of (113) to (1.15) co eo i not sicent, however, £0 Sete THis hecause such a procehire dos aot lead to 8 unique rel. The problem thar remains therefore i to determine which among numberof posits for 39, the sltion belonging tothe boundary conditions stated in (116). Each soliton for Jy Si = 5 charscterced by an integer, sy ach that a cofiient in one of the ‘equations haces, G(I-A\-b)"-1=0 ee » aay where given by Zeb. (18) “The solution foro Se then ira | (19) wile for r2 qthe ecurence ration fro-aye-wy"—t pn 20) a2 completes the solution. Let or carry this procedure through explicitly forthe ‘seq = 0, when none ofthe 9 values 20 Tn the case q= 0, equation (17) ves aa am snd exgntion (1.20) takes the oem, (1 7 1-0-0 (123)‘which for] <= 1 cam be writen to uficlene approximation as a 1 oa See Se 29 Assuming for the moment that this ese q = 0 belongs co he specified boundary conditions (16), we could say che appearance of the exp (rl!) factorin (1.24) something of a wiumgh for natural selection, for ites of the 3, value sharply for 2 ~1/}|. similar teament for q # 0 modifies (124) Z 3, 1.25) al-o _ivnga sila esto but with dstibution for population membershaving mie mt a2 with p* and mé hemologous, and m™ homologous and p™ and Ihomlogous- Nom join up the pieces but with >” and" exchanged, ving the reslean fice, Prmopte mts pm, mts pte @3) ‘The quae (2, 2m) therfore becomes (ple mt pm mee gte m m) e4) the underlined segments being those which have been exchange ‘Salsequene division ofthe cell containing the quartet (24) are controlled by an onanizational ren on etch chromosome known a the centomere, fkWhich for defntenss wil be taken to ein the exchangd pices The int cell division then gives (ox m+ pas Ms mm) yi Bm) + (ph m+ “m) as) the two paso the right-hand sik of (2.5) being the genetic antes af the vo daugher cells the empire fn what [have read appenty being thet the ew paternal centromeres go together a da the rwo maeal centromeres Each ofthe daughter cllsin (25) then goes int to fer el, (ams pe mt) 9 (p) + nts pe 06 (tr m+ p,m) (+ mM 9) +m), on so that the crigial quarter (25, 2m) has divided and sublivided afer ‘rssver into four els each containing single chromosome, whic may be cither the orginal por m coming through unchanged, or the mixtures (+ m+ p.m! + pm) ofthe orginal pand mle abo powible that more compler miatures are formed with both p cheomouomes exchanging Pieces with bth mchromaiomes ‘Returning tothe fill complement (2P, 2M) existing mediately before meiosis there are many quartets (2p, 2m) and no consent patter cece in crosover between one quartet and another, che pieces exchanged in slfferene quartets being diferent Norn che owe sucesive cel divisions i there a consistent pattem a to which ofthe four pow from each ‘quarter goes oa particular gamete. Hence the posits for variation are immense, withthe parental genes being shuffled o an amazing degree in conlya single meiosis. When all the gametes podced by an inva are ‘taken together, the shufing stain a considerble faction of the immense ost for variation chat exists between the chromosome sets P and M. Notice thet ching takes place within each separate individual, not ‘when male and female mate to prvuce an fing: The ner bas (P.M), ‘with P che parila male gamete and M the female gamete tha happen to come together Is P and M separately which have been shuld, From the A point of view ofthe fering she paternal gandprens’ genes which are hulled io Pand the maternal grandparent? genes iM, Shing i 60 generations bok from the present generation Inthe sbufng procs half the tenes which our grandparents arsed to our parents have been dans ‘View oa the point of ew af grandparents, no mediate mixing of snes cceured in ther immediate clren. Ming occured inthe srandehiren, ‘which is pechaps why the relton betwen children an their grapes fo clear diferent from the relation with their immediate parents. fo 2 enti sense nothing isoallyschieved between mal nd female uni nthe ‘Scond generation, their grndchuleen are ben. Tra rasdomly matin population, genes circulate very rapidly indeed Inonler to make the following statements more precise athe than for any reason of principle ee us omit selective factor forthe moment. Alo et the popultion N remain stable fom generation to generation and post a highly egalitarian society which every iil i 2 parent of to surviving useing, Caner the old paradox. Fach individual in the resent ereraton has 2 pens 4 grandparents 8 reat yrandparens ands on bac fo 2 ances G generations ago. Br for G > (faN/En2), the name of ancestors om this reckoning exceeds N, which impale. The err les of ‘ous the implicit asmption tara ancestor diferent: One ca hi tf genealogical rein a evened ime sense, with tw banches hack into the previous generation fom any id, with our branches into G = 2, ght Erachs into G = 3, and 2° branches in general When G <« (CaN), ‘there will not usually be a ath among the branches going hack fms the inlvidul in queson to particu nivel exiing inthe poration G tpeatons ago, When G = (2xN/n2), however, cere is usualy path fing ffom any individual in the present generation to any parcular individual in the population G generations ago. After G s (EnN/ Pn) senerations most nv in the current population have ancestors in ‘common, while for G >> (PN/fn2) there are many paths connecting any tedividual today 1 any specified individual G generations ago, counting paths among the branches a being differenti chey have any sequences of ‘generation hac ae diferent. C= (laN/fn2) is renelably shore number of generations, for [N+ 10% enly about 20 generations, Takings himin generacion tobe 20 yer, in only four centuries a population of 2 maiion indidbals who mate at randoe Become related to each other. Fnezasig N to 10" individuals only fens Increases the mixing ime to sic cnturie. This kes nonsense ofthe highly ‘este family connections of which sony people at inerly pea By eparting ou a small fraction of N and by esting mating to inva within che small fiction, a vighter emily” can of course be achieved ‘Through deliberte mate seletion aricoeic fies an eases can be ‘rated wich the tebe genetic consequences tobe cnsilered in Chapter, Seppose there ate ~5000 genes 1 a chrmoeome, with aout 2» 10° senes in ll (P, MD. After G = (CnN/fx2) generations, the average eagectaton for the numer of genes thit we have teeived fom each individual who existed G generations ago it ~2 = ION, which fr N= 106 ‘only 0.2. This ells that mest of che genealogical ph inking us to cut dlistat ancestors cary no genes. Although the paths actully exited, with 'n sca firing being bam or ever ink of path fom oe generation to the next, mos paths cary no ene. This because hall the genes ef se srandgarents are ot whenever an offing i bom. we denoee prseney Indias by I yw ly, and Ube which existed G generations ago by ING), 4(Q), IG) a path connecting 0 1G) becores lees es likely to carry genes, andso robe a generically relevant ancestral connection, {8G increases toward ¢N/En2. Mest ofthe pth fom aportcularpeseats bay ivi I c01(G), 1G), (Gerry no genes hit there a ‘ccasional path thar cars a whole Hock of genes, thereby naling the average valu of genes per poh robe 02 Ieiseaywetimate the sb ofthe occaonal gene Mock receive fom an ances ofG = (faN/En2) generations ago, Stating wth the chron they wee G generations ap, and supposing one ctosover per chrome er generation, cher wil ave ben G Ereskgs points so that come wl Fave the effet of choping the carer chromosomes int G pieces each wi ~(3000)6) genes, ForG = 20 eis i ~250 genes Thus occasional, om one four ancestors of 20 generations ago—an anceste at random —ne inherit wo oc thre funda genes, arm the verwhelming majority of ances, ‘oth. Thisexplans why the population sets so varied nt fine deal and ‘why a fist sir there seers tobe no thyme resem iit From anyasgned starting point, csover dives the chromosomes nto fine an ier pieces (which are, of ue, consti being ensemble) as time es on. After ~5000 generation the paces become of the oder singe ge, wit the entire ene asocationsone with nother changed mh Ae ‘what they were at che tar. For humans this is appoximatey the length of time tock to the emergence of Cx®Magnon man, the suly supposed ancestor of modern humans: Taking N= 1 in Ce Magn ies we would therefore ave =2 « 151N'=20 genes fiom cach of ou C-Magnon ancestor Unlike the situation (éaNJén2) generations ago, for which we have no crete connection to mt f ur ancestor by ich, we hae, oly enough, ‘rather unoem connection to our relly distant ancestors, This achieved throwsh the immense mini of path tat are oe G le. Most paths agpin cary no genes, bt the great number of them eornectng to any 1G) atively produce an average ofa few genes This when G becomes age that crossover has chopped up che original chcmosome into very fine pices To summarise 2 curious sitition, we each have a strong genetic conneccon 0 our mediate forebears and to recent nests shown in the family tees, which people are anos to know shout tothe extent that ‘onsteucting fly trees for hers can be quia profitable line of snes: Expenence shows that after a han of generations sich tees eseme fenposably dfs i they ae at all complete. Profesional inthe business then mis of ranches by the dsen Since oped branches could be just the ones that carry blocks of genes, the wees become biologically meaningless. After onl afew generations precise deal rherefore becomes les, and we have to ok inte to averages. Although che average Engl peson day has parent-to-hld paths goin hack wo a considerable fetion of thefts of Tador En, most such connections have no genetic significance, Some do, however, with considerable Nock four genes being Aevved fom individuals whose identities ae unknown to wi—the individuals could just as wel be Shakespeare or Henry VII as anvane ele. CCarioulyenoush, the chance of an explicit genetic connection existing to sn ihabitant of Roman Briain 6 gree than to an individual of liabethan times, while forall reser ime pans bck int che Stone Age, ‘the chance becomes geste sill and ultimately, fr our dane Cxt-Magon neertors becoming high. An outsider who observed the sage of evens ‘overa me scale of tens of thousands of years woud probably hinkof ws not as ditinct individuals but a one create, rather a8, genetical, we may think ofaswarn of bes ust one bee a spied that Citas donot we this consideration as an argument in thee favour fi ads ogc che chic of tweating your neighbour as yousel.{ew be recalled thar the average numberof deficts posse by a indivi forthe singe porent-eo-figring model tae in Chaper Twas 2s, where 1 was the rate of cccumence of defects per individual per feieration and s< 0 was the elective penalty imposed by each defect, taken all whe ofthe same sever The numerical vals conser in Chapter were= 03, [p= 00, for an average of 30 defect which sir tothe ‘ube of chremoscmes found typically inthe cell of plants and animal (Crsover apr, the random choices at mein of whole chromosomes, with a gamete sometimes getting a pchronosome an sometimes an chon some ffom the P and M set, aleady decouples favourable mutation sccuring on a particular chromosome from defect present on other comasomes. Only defects onthe same chromasome can therfore ttre with the penettion ofa favourable mutation. With the numberof defects per chromosome of order unity favourable mutation i already halla fice to show through the dfets, even inthe abwnee of eowover This no due 's the reason why the generic material of plans and snitals i indeed fragmented into an appreciable numberof sments which can be treated independently of eachother a meisis—rtea of beng resent esensialy ata ok sinker Des wh i > -001 we ly opel why snulple chromosomes Crosover peonit a stil ner gration, which i to say decoupling ryecpsiate to smal sleton facts than thove suid in Chapter 1. A simile analysis that of Chapter 1, bu for [s] = 0.0001 and with these 1.203, woul ead to the average inva posesng~ |e] = 3000 dec ‘wth ~100 present on cach chomasome. If fivourable murations with 5+ 00001 ae to show through so large numberof aes mutations ate for diving chromo ino pisces les than one percent of ther length and ‘of then easerbling them randomly & neces. Tis jst what cosover operating for upward of 100 generations succeed in doing. A few dvsions ‘sccuting in each generation, efected by the device of exchanging pices lecween a p and an m chromosome, des the Jab splendily provnke the exchanged pieces ane andomly chown at each genesis, which appears to Be ‘he siveon, Te sa far inference fom the exitence of emsover and fon thesis to which both plans and animals go in onder to maintain sexu wero duction —shifs ranging fom the devices of plans t secure cos-olliation by tases, to the pheromones employed by insects themselves to the gaudy fe fantail ofthe peacock, and of coure to human examples of which there i ‘esenllly no limic—chit postive evlucon must tum on minute advantages fvith = 10" or even low. Otherwise simpler stem woud be len, 8 for insnce fragmenting chromosomes Inco smaller pits, or micro cthomovomes, such as ae actly found in bir and repies. The later ‘per, appaeney not being suficien, was abandoned in mammals "To ad mathematical subtance to what as jus been si consider 3 sitaton like that tdi in Chapter | in which nana slecon checks the flood of deererious anton from overwhelming species, Thiscan only be done, a8 we sin Chapter I through the random incidence of murations secting up factions in their number between one individual and another [Nana selection then dstinguihes berwoen those individuals with fewer and thowe with more than the average number, sy, of defects the adverse mutations all have the sme jl the balance imposed by natural selection follos the Poison distibution according ro which Hop - a8) Ht exp —H es) isthe pokublisyof an inva at random having k defects ‘Sarpase now that favourable mutation of selective advantage S> 0 is posed by a faction x ofthe population, and suppose the favourable mutation co be uncorelated wich the defeces, by which i neanc that indivi with or without the favourable mutation have the probebilty (2.8) of posesing k defets. The problem iso determine how x vate fom ‘one generation to the next, the population being eontrsined by the fwionment say fied Ta weal eetern wich the double see of genes (P, M) these ae three posible fora favourble mttion—ie maybe present on one o other of DP and M, irmay be present on both, ort may be present on neither Since in ter chapters thew chee posites will be erated in detail, is favourable gene and 40 enjoys a selective advantage 1 + S, of not. The ube of irivng ofpring for an individual with k defects and with the favourable motaion can then be writen a @(L + S)(1 [i while an individual with k defects bur without she favourable mutation leaves an ofsverage of {I-Ie} ofgring who survive to matty, where a is a ‘normalising actor chosen 0 thatthe popultion remains fixed, hat ty afeaesyt—o) SAHA exp 1 a9) sig the sme meth sin Chapter ocesin dels we ave xe = ox(lts) DU-|sp% exp-w—, 210) a ree whence edt. all) &. Ad, em ati de _ yall-2) 1 a 1+Sr eo which is jst che postive selection the favourable gene would have in the absence ofthe defect. If the Poison dtbution (28) were replaced by probable py, =I, che resule would be the same. The rule depends only on uncoupling che favourable maton fom dhe defers Justa ic makes no difrence iu exp — iis replaced by fh i makes nodference tothe derivation of (2.12) [in (29) and (2.10) replaced by [The advantageous mutation Sis alo selected independently af other sbrantageos mutations, which mean that advantageous mation lectin ral with eachother, instead of only sequently ae cre would have foe ‘the model ofthe previous chapter fone wer to somehow be rid ofthe more feoquent deleterious mutations i that model. I in the single patento- cfpring model one had eo advantageous mutations S, > Sy > in diferent ae lines and no dindvantageos ones, the posession ofS; could be wiewed a8 & lndvantage compared tothe possesion of Sy. Hence, afte Hines without tither mutation killed out, S, would proceed to kil out Sy tn che sexual ‘model with crosoveron the ther hand, and; go tei separate was 30 fermi both wo be favoured sleeve "This Laer advantage of sexual reproduction sce to be the scongest| argument clames inthe books fort over the asexual model of Chapter 1 Fhers The Gentil Theory of Natal Selon caves the point in the cult elliptic thar were xo characteristic of Fisher. With quite some Searching one can find in Sewell Weights treatise in four volumes, velson andthe Genes of Ppalatns (University of Chicago Press, 1988) and more directly and clearly i J. Maynard Smith’ The Elion of Sex (Cambridge University Pres, 1978). What one does nt find, however, san npeciaton of the realy envi spect of che mates, that only with sex reproduction accompanied by cosiover can postive mutations make Iheadway agai the deleterious mutations which occur with far greater fiequency, and which otherwise woold swamp the alvanageous mutations, ot permit them emake any heady tll‘Tie immerse simplification of being able 9 gene indepen abies mel wth rcsover penis more sophisticated mathematics to be ws mathematics thar combines leton and shane cts within the ame formalism A wont futon fist however Ona bond penpectve dhe selective factors contd by Aeron genes re nerd, Whee encynes cooperate togther in pope—for example, heeee ee ‘hiny orso enzymes wit functions inthe proces cf ccs, or the twenty ‘orsoeytochromes involved in dhe prcest of electontanfer complicated functions of al the ensymes ina group foe the performance ofan ‘ngs, rather ashe performances af solder in bt depends on those ‘who lank his 2 wel scr his ow inberent quits, Yen what allows [sll consider the seletve factors of genes be inependent of ech ‘othe, and here are two reasons fo doing. There no magic abou the term “gee,” and so fa the mathematics iconcemed we can take ae of the kind just mentioned as ating tngther to fn kind of apergene st any es Tongs the DNA forall the genes of chest ae sficenly adjcent to eachother fr them to he egmented coll rey by cresvee, ‘The second reason i mathematical, namely chat when selective Factors ate seal compared o uni as they are normally supped ob in neo Darwinian theory even complex functions can be ina by sable ‘expansions, much as potential functions in cami ae linearized fo sall motions eventhough they ay depend on many coordinate variables “Tothis pine we have pase ina ingle tp from one generation to the ‘ext, relating Frents only to che minority of hee offpeing who srvive to tcome parents themselves. This ws dane by writing a1 +s) asthe number of mrviving ofpring ofa paren with some selective propery A, compared ‘0 a alone for the numb fom a parent with the alternative propery adjusting os as to mainain a fed population. The factor 1s was thus the elit fines” beeween inv with A and thos witha a concepe with meaning in relation t a specific environment. In general, “ines” ‘cannot be determined by genetic alone Let A anda ee for example, to the colouring ofa female ground-nesting bith, with A giving cana agains hawks in one geographical locbty an in aneeherlocaley. The ‘value to be asmed tos evidently depends on which locality isin question, ths sitching sgn fom one to the othe Inaddison to cbvicus physic facts sch oer ul sl content or sonal temperate rane the Yervionmenc” st covert ony the presence of other species but even sutle aspects ofthe species unser consideration Knowledge sa major pt of dhe preset cay human evinent er example Jn the cary human communities of 5,000 years a even rather moderate pene 6 wah soa ial hoy hing See ioral "Tae ta ange ions spcng a age at of gee selec con ven a uicler moment de Ea fen an ese tage events ed th rec ie there ee Marre the envionment la crate of chenang wth deat telinnns Hens arate ath population atin i fed vient cane eich set le le hy sd Concept Oy oe precy fom 4 mater pt of ew we cx ‘Rf he byob oil poplin in acta enone feoeing 8 tigate. Neghcuod scans can Fe Fad poco toch boars pet th ons the detativs of cons ating ncn of aren enimenal sif Lat cme ow to the ingore quo of fw aden all once Whe afin red om pas to ving ing shee aiff romaine factor michitey onited The bering iid topic of de nero mili fpeng or eey ne ht ave fina, Wh eth dee the met o hn tht five mpd the next genction! The hipe mami offen fering rove od ro get ng feeling ata ania The sulin own vic joel heing creat ee 0 hee sme ln concrete the ele tie Se heh moony poplar olson ave ened ome tbat he ering pet wre ldo pots 100,00 esto i the ptf pe nce cha te ew gel prt ce ecto gow tm, Tis hob wg na efor eo way in which 999999 ovens oun ob cose sd th et {Pal The igo aoa op othe nthe nt en il {Powis ton wma a heen hao hes thoi pets cnc ne When cho pe thy a frie pcs hich papel wag, Whe mie ich aoc be Lawn top he i cre pce ich an ime Had of ivr da eo em acon chance on he ‘rm mts and cme Wie Nor hea poplin, aking NV tobe oan fm esr to genom Inthe ml whe sad bl wl fe a)sumed that M juveniles are produced i each generation with M appreciably lpr than N, and i wil he farther supposed that M ix Independent of N. Cleat thiscannot be sry tue, since there canbe no juveniles a ll when N= 0. IFN fll too Towa species can produce ‘enough vere oexpoit the niches avilable ot In uch eumances he species becomes "endanger" a one says Bu endangere specie aide, sr many juveniles ate praded that we can conveniently take M fied Letipand I~ ohe che frequencies at ie €= O ofthe alematve fom A anda ofa paicular gene, menning that ofthe 2N ets of chromosomes powesed by the N indivihals 2N have A and 2N(1 — 3) have a (Omizing seleesion forthe moment, what can wesay ofthe frequency of A in thenext generation, ar Icing che peneraton interval asthe unit of {Let the Nindiiduas mae at random, sn which ese any chromosome set passesed by any ofthe M juveniles inthe nxt generation has a chance of carving the A fom of the gene, and the probably of the A form, appearing 2M times i dhe next generation wl be the tem in "in the binomial exganson of (p+ q)™, where p= xq = 1X Behind this random transmission ofthe A form isthe consideration that each of the N Individuals produces @ suply of gametes even lager than MIN, with random mating ofthe N individuals interpreted as choosing their gametes st random, M female ones and M male ones, bot having athe resuency ‘ofthe A ype gene. Is possible to define random mating in other ways that lead to reas that are ferent n deal bt nein principle Teens in the expansion of (% + T=) can be approximated for |M>> bya Gassondistbution of variance 2Migl] x0). The probably thatthe fequency of les beeen + and x + dx among the M juveniles of the next generation i a7 } en) eee =e) ee {inthis Gansinn distribution. This provided isnot lose ro the end pois ofthe range 05x I, and taking M >> 1 otha the inegral of (3.1) over Oa1 ss esentaly the same a vermox = ‘The M juveniles ate seduced to Nat maturity, with the ratlo [MN highly variable rom one species another Thus MN is ~10! othe of Iring bu only ~5 for bl and for humans under primitive conditions Without ection the reduction from M10 N would again hea random, in which ete the prabliry of te ne fequency yng beeween and ¢ fimong the N individ a macy would be shoul the gene feguency among she M juveniles happen to be x The tal roability of the gene frequency Ii beeween x and dst matty therefore giver by mpg (3-1) and (3.2) and by then iterating with ForM>>N>> 1, a(x) aS the Dia dela function, whence (33) is simply “| M(5,-x0)° wy + os) roll) Yalta otthe same as would have been obtained by going immediatly from the N ius at = Oto the N surviving ule a= , the als who wil give rise to the second ene at Likewise, the probability that the pene frequency at c= 2 es hetween van ay dy is + 66) when the frequency at = 1s taken asx, Combining (3.8) and (3.6), the toca probability ofthe aul inthe cond penerations having a eguency of the genotype A ving been sand x de given by famedeeae |e © » aadt=a) Nala) of heh es on Since the population number N canbe taken le, say N = 105 the ‘exponentials in (3.7) give sharp peaks abou x and abouts Hence, so long 83 is not very clove either to aero oF unity, i is sicently accurate to replace (1 =) by (1 =) and aso to expand the range of integration N YPrlt-) 68) 2x(1=%) N= t] a -f}- A simular argument going fom ¢= 2 to the thin generation a = 3, and so fn tothe rth generation at = gives rr f ex - 69 \rali=s) { forthe peokabilty ofthe frequency ofA lying between xand + di afer + generstions. Tis sao lng asthe succesve spreading ofthe exponentials fom generation to generation doesnot lead to values of with appreciable probly and such that (1 =) is siticantly diferent fom (1 ~ x) ‘When r becomes so large that this isnot che cae the imple progression from, gcneration t generation most ease, anda more comple procedures then, ‘eqre. Before developing formalism for sich a proce, le ret £0 ‘what hae so far heen omited he effec of election on dhe rqueney of A, Fach genertion his been considered to const of tw stage, ist stage rm N mating als to M juvenile, nd then a second tage fom the (M jweniles 9 the N’ mating adults of the next generation. Although selection can enter hoth these stages, the second & anally the more important, and nothing of principle wl be let fe confine sclestion £0 ‘The frequency of A among the juveniles being taken as the number of juveniles with A on both ehromesome sets Me to within auction tha i only of smal effect compared to the Mactutionsakealy seed above, The numberof heterocytes with A on one cheomasome set anda ‘onthe others ZMs(1~2), and the number with aon bo chromonone M(L =), Write o(1 + 5) forthe chance f an (A, A) juvenile surviving to reprodce the succeeding generation, write a+ s) a the chance of 2 heterorypous juvenile, (8, ao (yA, surviving to maturity and efor an (4.4) joverle. Then is deterained by aan [+s)ie +2(1+hx)s(1-a) 40-9] =. G10‘And the ssemaic change ofthe frequency tx + dl in the parents of the next generation sven by ane B) = anfanrse? s20+09)x0-2] 040 ‘The righthand side of equation (3.11) takes account of surviving Ihterryptes having ane chromosome st wth A, each surviving (A, A) Individal having two chromosome sets with A, and each surviving (oa) Indloidal being without A. From (3.10) and (3.11), oS gy bette Lr 6.2) IF [s] << 1, (.12) cam be writen to cent accuracy é sx(1-x)[x+A(1-25)) 8.13) Inthe special case b= Yi, (13) takes the even simple fom 64) Except for the factor iy this isthe same asthe effec of selection in the sexual made of Chapter 1 ‘As ells the righthand sie of (3.13) being sto fr x =O and x= there hid eto for G3) In oder that (3.15) be a permisible vale forthe fequency of A, ti cesar that oss. 619) that h2 orks 0. To decide the stacy or otherwise ofthe equilibrium, value (315) in these cases, diferencia (3.13) the requsement for stably being ‘as A MID, which is saciid Hither > 0, > I ors < 0,5 <0 Sshle stations with = 1(2h~ 1) ae know a lance polymorphisms In studying 2 balanced polymorphism, ic is really unnecesary to Aisinguith the wo cases + > 0 and + <0. The sclecive parameter as defined ahove by the contin thatthe ratio ofthe survival capabilities of juveniles of types (A, A) and (ay a) be 1 + 5 with the later in the denominator when the ratio is taken. Bgl, we could bave written a as the surviving faction of rype (A, A) and a1 +5) asthe surviving faction of ype (6, hen the ratio of survivors desing # would be inverted, wih the sign of ever. Choosing the definition chat leads to a specified ign of, > Osay determines the condition h> 1 fora balanced polymorphism {tw exist. The esential condition for a balanced polymorphien fs thatthe heterargotes, (A a) o (a, A), mas have a selective advantage over both Dhomorygoces (A, A) an (a 2. Stochastic fucuations fiom generation to generation wil cause the fiequency x to be constantly siting fom the equlibeium value N(2h 1), ‘bu because the equim i able, the fequency always recums eo this ‘ale, which i ths the complete solution t the behavior of in sch 3 ‘ewe. Although Ihave heard expresions of pinion tothe contrary fom bolo ulaned pomorshisma ae nally considered wo be rae, and 50 {will consde them to be—ctherwie dere would be Lite more to do, From here an, therfove 1 wil spose tha A does noe sais the condition forabalanced polymorphism. Also ftom here on will make one or ew mince changes of notation, as well as aking [st be smal ompared to unity, in which case (3.13) is sufclently accurate In che first generation che gene frequency changes de to election fom 2104 +o where fom (13) % — aso +H(1-25)] 0.8) In contast to (18), which i a clearcut Increase or decrease in the frequency of A according to the sig of the stochastic faction ofthe frequency, given by (35) for the fest generation, may lad 10 either an increase or a decrease of frequency. Combining (3.5) and (3.18), the rota of the roguency of A Ing between; and + ds afer the fst seneration given by [x 5 | Ny-w-n) VF) %o(l=%) Ja. om ‘And if issue tha x(1 3) ls ot appreciably diferent ro (1 ~ we can tp along to the second generation, and sn wo the yth generation, provided (1 x) noc appreciably diferent fom (1 ~ 3). Choosing by this terion, the probably shar ater generations the fequency ofA les Derwen sand dis given by a <6 Instead of weting the tes marking the generations by 0, 1,2,» esta mista change of notation we en Wee fe ye HE, shen (3.20) takes the form fe Yao] —) Defining “propagator” by Hatigtd) so - Memo at eee ee 5) the probable 10 fom the frequency xy of wne-nype A at time othe fequency xa inet, subject to che contin chat ¢— fg muse rot he so large that K(x) has appeal values with (1 ~») dieing sieiicandly fom x(1 — 3). To ive verbal surance thatthe later ‘Condition i said let ur refer to (3.22) as hentia propagaon”| ‘Change the notation now 0 tha yf ar times such that the infinitesimal propagator can he used sequent 0 tt) (Df «the sage of rime being thos broken up so that (3.22) canbe used teach step, Note ao that if insted ofthe gene fequency being specified uniquely at the inal moment t we ae gv the more general boundary condition at tcthacthe gene fequency haste probability dnribuion 9x ds, then the probability ditrbution ots, ds fr the gee frequency at cme fs siven by ta 8) = fs 0) ol) ‘ a9 Forth nest for 04 when he se Wy $e» 4) Jato: av) oe a) . Om BeHa. 55 4) beng given by writing, 39 F536 9 and fF] 6 sxquaton (322), with, defined by =x)[n+H0-25)). Weed. 629 Pcs spy ep 9 i Hon n)=f CC tha) ol 0) AS) ay 626 This rele cn He writen comely in terms of a finite propagator Kea 8) dt) fat Jyla) ret) Ai» G20 where K (Set ita) Theltnnton ns) r,4 028) wich Be “The present formalism hs analogy to problems in statistical mechanics An which repeat inter ike (3.26) are sometimes converted into asinge- path integrals that one can wonder ifthe present problem can be expres, {sa pth intel. With anitabl change of the variables it can. Defining 8 by C080 =1=2tp, P=O Laer 30) therangeof @, comesponding 00S <1 is 0S 8,5. After seme reduction wwe then ave afi-x,)=tsinte, 630) 1 Asino,d0, 3.32) 280 p dp 632) eleataiecngyan-n] 5038 —f-<om) Teil be convenient wo let the tnesteps a: ~ 6 all be the sae, € 3 Defining 83, by Sep erneries Peo ee 039 uation (3.28) can he expres in the form : Bo 440, Po “The function A) can be thought of path going rom ft 8 by way of atime ty ya time ty 8 at time yy with he path consisting of ‘ait line segments between consecutive values ofthe time. La ce (8.0) plane star at fo and go by «straight line segment to Ot hen by a right ine segment 8 and 30. ui sreached. The multiple fteegal (340) isa suriation over al such functions 6). Moreover, for el KG, Ors) a0] 00 <9 nf fo smabrosoerolfn oa the tne integral beng taken slong At) and so being a finetonal of Using noetion introduced by Feynman (eg, R. P Feynman and AR. ibe, Quanton Mechanics and Path ites, MeCraw-Hil, 1965), (3.40) Ths the formOh Boy) oa) Given thatthe gene equency ts the pokubilty ofthe gene fequency being ats therefrecbainable by 2 summation overall paths going mn (106 tha saci the condition of being confined berween @= Oa Om, swith each path having a weight factor o- nife- sne-saasrt}] 0) Inqstnum mechanics, che problem of patel in a potential eld can be solved ina broly similar way, with K(x, 2, &) being the wave function a time forthe case in which the parce sat at de, Hi ‘quantum mechanics an experimental procedure were se up for determining, where she particle happened eo be a cimes intermediate beeween ts and f we could sy chat the patil followed certain explicit path. Bur in che sence ofan experimental procedure the wave function K(x & % 5) recenarly cbained from a summation over pats, the procedue being similar to the above discussion of che gene problem. If in che later me take 2 Took at a particular population, in suficene detail eo determine the feequency ofA at moments intermediate berween fy and t, we can say By shat explie path the frequency went fom its value at ois value a Bar ifwe do not look explicit atthe population eis imposbeto sy what particular path has heen followed. Just ain quant mechanics all we ean do to asign probabiiesinelving a summation overall paths. ‘There are two diferences from quantum mechanics, however. Inthe laser «potenti function ener the time integral in after analogous to a ia (6.48) only linearly, whereas the selection teem in (3.45) is quate in 5 ‘Although second-ole srs in + ean usally be neglected for 3 << 1 with Jimny, chs & not so in (343) fe may be noted. Excepe for sal ene (erences tthe tet ny muse be retained in cterpting 0 evaate the pth integral (342). Alto se may be noted that in quateum mechanics thesndex ofthe exponential athe path cera spel magia instead ‘Gl being real as in (342), a ccurstance which i analogs to statistical mechanic twas lend sid above. But the bigdiference i that a particle confined in quantum mechanics toa coordinate range 0+ | wll eganded as being restrict bya box sth pefcedy reflecting wal, whetea in the gene problem paths which > tore Dorey a= 1 are not welled they stop. At x O the gene-type A frcomes extinct and cannot retum, whale at x= 1 the type becomes poset by every individu and the station stays that way thereafter, "Thus the gene problem is lke a particle in a sticky box with the particle adhering pemanenty shoul touch the walls ofthe box "The efecto extinction and of xing inthe gene problem is that K (st fo) de oa eclnes as increases. Waking Py) the probability that by time ¢ the enerype A has become extinct, snd denoting the probability tha & has score fae by Py (0), conservation of probability gives Pal) * Flt [L439] 4 G45) Moreover, 0.48)For any specified path the fmeronal given by (343), 1] can be caluated. Then K(@ ) can be obtained fom T1019} 20(9 i through quadraures performed at times intenmediate between tend f remembering that che weicht factor Q= @/N tenet, where © i the time-step employe. Since K(O, @ ) with x= (1~ eos)? yee K(x, xt, three final qudtatures in 345) to (3.47) determine asl) and Pa, 50 completing the solution of the probe, since with equate computing faites numbers coud actually be obesined. An alternative method of solution willbe considered in the next chaptet, which for the mest part snot tse than (347) but lead analyialy to Page Pit the iit Chapter The Solution of the Single-Ge Problem by a Partial Differential Equat ‘Problems that can be dealt with by path eee ase or hice been ve The pune nck lll een otc essee scmetinesdeerminabe, Problems thar can bedesk with by path Inte can ako be sod by pail diferent ‘cron Some tvs res a thane may wither ae et ‘fut wth tector way The pth ing mtd sb ine ier Both etic ae nee er il eer ge Inrral atough for raedced queries, detlons ae vmetines biel, Thi 20 in the prosne poten ited of aking fr compte deteminaion ofthe ite pope KG, 354) we ak the ‘mule fates over te enti me ngs < oe the gene pe ‘Abecoming iter aed or extn runs otha es pra pelem Can bled by the pata diffe equation method. Since the wa her inthe 192 it as en Known that a aia > 1 and 1 ny mene, Hece mut he claw FR 0) be “Gps doer fom and we can ep (45) by 8 Machin inincemacl x(1-a)[x+A(-29)] bat i, & Vy gfe yess Bad af Ft = sx(l=a)feth(~20)}+ 9(x—2) LJ + ao‘With [et — small, sficienely accurate to omic all but the Fst ewe ‘terms of (4.6). Now (42) car be rewrite 8 olety(e—r), ts xat)ole tae AD) by which device the fist term on the right-hand side of (46) becomes teaafered from the right tothe lft of (4.2), and expanding the left of| (42) fee 2 sll we have seaneecnfoatere] « “heel Memtearet] “EI | ae | ae as) eee eee “Toobean the equted portal diferetial equation, we have to inser (49) in G48) and then evaluat dhe reslingfnepal wih respect to Facing this tak as best one can, put Fea (410) changing the variable of integrin fom x" Because ofthe sharpness “tthe exponential in (4.9), suficient to evaluate the other tems inthe fatcgral (8) with [sal that in ascending powers of x Thus Cs tot 2so(e)Ja . aD ag atts] wane fea) oF 4-29) 2 +0(2) any And expanding (a) about =, stecyeotattenspMlt Los... a) Ineing (41), o(esr)=o (a0) R98 Lala-2y22 + x-9228] + + fe[ecanié v0 23 aw a‘Mlbeaio + Felsen Hence, 0 tems of onder the righthand de of (4.8) is baal [acs AMHR Ee tah oo aay) the range 0's I lelding the range fie =-to for, Allthezependene ‘teens in (415) can be evaluated upto oder © by wing 8 ws = | (4.19) snares ste cnet eae etree SE Hence the roquired parcial deren eqution is 2242 9)= aAlbs a-95 8 1-22 - BI} . (1-x) aware rel (4.20) Let us consider, fit the cae where A is @ neutral mutation, that 41=.0)9 =O. The separable form o(s)=Fe) ox: Eten) any Is then a solution iF) sates the cednay differential uation s0-9 ££ 420-2 +(v?-2) Fao. aan For w ea (4.22) has the form ofthe hypergeometric equation, which in canon frm is 0-92E sfe-lorbona = areeo 429 “The solution F(ab 3) of (423) eal to unity cx Ohasthe series form ala+o(b+) T2c(er _,ala+fa2)-b(0+1)0642) 3, T2-3:c(e+ e+?) an oe Flabress)=14 beewoe. ee enviing coffees Hewsen (422) and (423) and noing tat Pla, by 6; x) = F(b, a5 5x), . 3 feet a WG send (425) determines the solution of (4.20) subject to oe) having the separable form (4.21) ‘When w isa member ofthe sequence nin + 1), = 1, 2) ou «the solution takes he form F(1 2,2 +m 253) for which the series (4.24) can ‘be seen to terminate, The seresbeeomes a polynomial in x of degre x"! ‘The esental point ofthe ahove anal now emerges, forthe polynomials (=n, 21 2:x).m= 1,2, areacomplete set. Hence the most general solution of (420) can be expanded in terms of them, 2+m22) en - septal a [av (24) Sant where By.m = 1, 2, are constants to be determined fom the intially specified form of 3%) I for example, the gene frequency has a ‘unguely spect valu 9 ime ols 4)=8(e-%) aan here —) the Die dea fntion andthe are be ctsned om Ep, Fn 240;2; 2)=5(x—%) 42) ‘The polynomial Fry 2 + m 2:2) have the Saher wef propery of ‘ing ohogonal wih napeet to (1) as weight tor, of es cee cee eee ER Jot -mz-+m2:s)R(-nden 253) a(l-ade |. +a itmen (429) ‘To determine fin the case (427) multiply (4.28) by x1 3) {I m2 +, 2,3) and integrate with respect from Oto 1 All tems five seo on the let except n =m because of (4.29) and Baas) elm 24233) Pays |at-syeti-maemaisdaen) a ay(len) F(lmatm2:sy) meh 2 30) sang th coins om (430 et (4.26) sles the pce ine tchavior of neutal matin having deite equency 58 “Thus the inte propagator Ks, 6) 6 ven in he nea se by (ts yt) Slay) moe Fm 24M 25) «resonated «an a remule stated by Kimura in his book The Neural Theor of Molecular voluion (Cambridge, 1984)For consistency, (4.31) must end to the infinitesimal propagator as 9 When s= 019 =O; the Inter (st 35.) Emenee | NG a) xl e) PL Helse) on Psy there i some elegant way to show that a 1-9 sll) Ente Qn F(t-n2msti) © nlnsit—) a _ Vaso) a) but iso, Ihave not been able to find tL wil pave the reader the cute misery I encountered in trying © prove (4.3), giving only a sketch of my caleulaion, which dined arrive at tsp in the bitter end The ouble is thar the series. on the lft hand side of (4.35) is dominated at sl = g by many tems at lage values ofr. One must star theefor it seemed me, by finding an aspmpecic fom forthe hypergeomerc polynomials. Those mathematical vade mecums with which modem pubes sek to ease the life ofthe younger generation proved tobe silent on this matter. However, there are relations between the hypergeometric polynomials and other systems of ethogonal polynomial, in pte F(l-n.24m 2:2) «| 433) - ee ee en eee eee 2 mast) als) F(l—n.240;2:2) [nd-2x)] . 638) where PI 2) is the Legendte polyno Pos) with cos = 1 ~ 2s (A tochol! could then be gained fom a known asymptote form forthe Legere polynomials, P,(c0s 6) lenamo sinf(n+3)0+] (435) [Now pur (435) in (434) and substitute the resulting expresions for PU 2 +1 253) and FUL —n, 2 #25) in (433), and then proceed to the norso-nquiste problem of summing the relkng series. The outcome, after an unattmctivetrigoncmerial reduction followed by replacing the ‘eciesby an ince, was indeed the right-hand side of 433), which atlas ‘convinced me that in mathematics thee is justice tough, and this one than you can say for mot ofthe oer activities of humankind. "This experience made me wonder jut how asl the result (4.31) ely {Ie isthe convention in mathematics for any pec that ean be expressed {ntermsof known factions ike the hypergeometric functions to be reared, assolved. As long as. procedue canbe mpecfied whereby any question about the problem one cares to ak could in principle be answered the problem is "olved" regardless of whether in practice dhe procedure really oould be carved out. Some lgictans have questioned such a style of argument, ‘Specialy where rita mathematical proof are concemed as for instance tuhete the so-caled anion of choice concemed. My own view ofthis old Controversy is that one has to dings sharply between procedures that relly could be pushed though feficlenr tube were taken by a sufcent rhumber of people, and imagined procures which relly could not be cried fut no mater how mach human efor were expended. The Inter | wou regard dubious, dhe former a8 permsible. There is no daub tha che present problem of determining Ks) fills into the permissible cls. Given 3, mumerial values for Kis, 6 2 &) at specified x, ¢ could in ppactice be found i one were mificienly determined about it How ‘Setermined would one have tbe? a‘Mithenatis « Brottion ‘The saving grace ofthe solution (4.1) is thatthe exponential factors cexple nin + 1(e~ 4) / AN] produce rapid convergence for tne differences ‘tof ander N. Moreover, the series expansions for F(L =, 2 +n 2:3) and far PUL—n, 2+ 2:4) terminate quickly fo low values of, Ths oe lange time diferences (431) cou be made wo yield explicit aumber fr the nite ropagitor Kix, 9) On the other hand, fr sal ine dlierences the series expansion (431) is impractical fr the rexons already discsed above—the convergence is strociousy hw But formal ime dfnences we Ihave the path integral method discussed inthe previous chapter Indeed, for {= fosmall enough we already have a simple formula forthe propagate, the infinitesimal propagate (stay. tg) =H 75.4) I Mlemson nimi Vrdft=0)(=) aafl)-t) 438 ‘Aste incremesit becomes necessary to have more and more tes inthe path integral which ithe way r increases inthe expression _ a «sn —f-< For 4 tof onkr N ie would epiilly be necessary wo peor abou a Ihde quacarresin order obtain K(x 6) fr specified. Wich 2 mover high-spet computer sah a computation would pot be out ofthe ‘win, but of course the sees expansion (431 is mach peefeable othe oth ieegral for lange ¢~ Ths provided the slaton factor & 22, Provided the mutation under dicusion is neural. When + 0 the Ethmetcal labour of wing the pth integral method is scarcely ft, Gihereas aremprs to obtain a series expansion similar to (4.31) appear ‘ovmed to alare: With the 29x tee in (420) included my ates to find general sluoa fle, Nor cold I find anything uel in well Town hooks on speci functions Yet remarkably enough, though (4.20) teas not helpfl forthe gener] purpose of deeming Kis, 6 x &) Sraytcally, the pal diferenial equation provides the solution to a ‘problem, which although limited i cope, i nevertheless important. Thi the problem of determining the cumulative probability of the gene A. becoming fixed (x= 1) and of becoming extinc (x = 0), cumulative over the whole ime interal fom x= spat t= 5 196-9 ‘Weingut (420) in full, 221 gender et-ofeemt-aaol 49 whens Phos Zl -ai)-sat-nfee na) 4 2) +6 439) “The lefchand sie of (4.39) the te of increase ofthe sta probublty of the gene frequency ring beowcen O and 1. The increase being negative, the fpobeblity of the gee fequency Ig nthe open interval (0, 1) decreases nd ic dows s0 tough what can be called an outlow of probability, an futlow atx = 0 representing the probability per uni time thatthe genebecomes extinct andanoutlow ats 1 representing the probably per nie tue thatthe gene becomes ied. These te the wo tenon he right-hand ste of (439). The cumulative probably of Fixing A i therefore 440) 43) Ahoush dhe paral diferevial equation (4.38) is intactable for deter rmiing K(x) when 5 ceuns out thatthe less ambitious probe of deermining Py, and Pay can ined be salve, Provided the special and unusual cases of lance polynorphisms that were mentioned in Chapter 3 are excluded, the gene-ype A eventually ‘comes ether extinct rfid, hat Poa + Fig =1 44) ‘That into sy, (590, 136 445) forall xin the open inerval (0,1. Note also that <= 0,2) and gtx = 1.) in (441) ate defined by contniy from (0, 1 ois endpoints stuation hae is common for partial diferental equations (ef, Methae of “Mothemacal Physics, section 10, page 324, R. Courant and D.Hilber, New York: Itencience, 1953) Hence at any xs (0,1) we have oe anne I EEE jem 2H = -8(x-5) 40) ic being supposed that atime tthe pene frequency is knoe tobe Xa or example xp L2N when a maton occurs. From (4.38) we have igre 4S [e- fea] ffro-oesse-a jroo] aan Defining ntd=foconar (4a) ® wether have ~8(e— 5) = Selena [eye n(-29}] 499) Comparing (442), (443), and (4.48), we see chat L = Lu (e=0) (450) Pox = Gy F=0) 1 aulHence the problem of obtaining Pi and Pay reduces to the problem of solving the ondary diferencia equation (4.49). xcept at = sy the Ifchand side of (48) i 2eo, and the equation | swith eo on the left-hand side hasan immedi is negra A fvtt—ayu]- 4Nsx(1=s)[+h(~2x)]u = Constant. (451) A solution for ue) stisfng (451) olds in oth the open intervals (0, x) land (x 1), bu with diferent constants om the righthand sd, because of ‘the delta function in (4.49) whic requires ds to bea seep function ares x= On the other hand, (2) is continuous across x =X Let C be the onstant for (0, 9) and Cte constant fer (4 1). The equation 4 (1-xju]-4nsx(t—x)[x+A(1-20)]e =C 6.52) for (0) has expl-2Nsl + 2M =] aan integrating ctor, whence (1-2) exp[-24sf2? + 2h(-2)}] ue) Dh =G/(%.0) say, OSxe% 433) =cfevo|-2e + Siaialy, xl=a)exp[-24s{2 + 2A(x-27)}] uO) cof exof-2nafs? +2n(e~ = Crt.) say, ayexst Continuing) a = equ cr(se0)=C-r(4-%4) Inegation of (449) frm 5 ~€ 105+ € for € << Lal gives wtf). BF hich fom (4.53) ae (4.54) reguies C and Cc satisfy c+ =4N From (455) and (457), poea OTF Ao) as + F(R. 0)/1Uh m0) ‘Now from (4.53) Ma)aC x0, and fom (4.54) He Mle as) (455) (456) 45) (458) (459)WIC as xt 40) From (450), (4.58), (459) and (460), the equi probabilities Parad Peo eern (lex F(¥.0) eva 2Nafs? +2n(x— x2) de . 4a) s(t) J exo[~2Ns{s? +2n(x—s")} ae ° (4.64) All that ensns of our problem so evaluate (4.63) and (4.64) fo various choices of sand h. As for asthe selection factoe# Is concerned, we are interested in both s® O and s< 0, nd in bh 2N | > 1 ‘The case 2N |< Ls eay deal with This ithe case ofan effectively neutral mutation, with fs, 0) na 1-12. From (461), (402) (465) which are wellknown rule alo derivable, awkwardly in my experienc, fiom the ses (431) and more easly by an agument given bythe weer together with Profescr Chandra Wickromasinghe inthe lecure note reprint ‘Why Neo Darin Does Nov Wink (University Cllege Cac Pres, 1982). "The iuerale (463) and (4.64) can be evaluated immediately forthe ce = which isto sy, —exo(-2Non]] 2 stefee(-2mm)-ent2ns] (466) evi 1-exp(-2%9) an expN) s(n) ~exl-28) sos) T= exp(-2N5) For2N pl >> I.an akan tation with > 0,36 URN, gies ews) es. secl 40) Pegs oP 8) Fors <0, on the other hand,= bplexp(-2Njs) = 0 Pog = I~ Foy = 4.20) “The theory only docs n prt what according to neo-Darwinan cance i spore to do~celeterus miions wth 2N | >> I are prevent fan ‘coming fed, Bt the theory doesnot a up all that good” tad nly a fraction # of advange mations, 0 that rd <<< I theft smal, ‘The station for other values ofthe parameter h is qualitatively the same. Ill ese with m= LIN << 1, 2N}s] >> 1, fl € ly we ave anf? +2a(e—2)] <1 for xsay TD otha ‘ot)= fel anf o2n(e—2 Jace 1 = 2) er soa) jel 202 +242) jexo[-2Nsfs +2n(x—2°)}]de >> £(0.%9) (47 Hence = flea) 1 = 7 TAT TGeO) Tox) © BET «4 We anu the ution reduces othe evaluation of $(0.0)=jexe[-2nefx?+24(x— x?) fe 638) sce fous Pa, 1 ~ Fg tsiained immedi an Peden Forthe ewe = 20, 2Ne>>I, ' . 4(10}= fexo(-2002) dr & foxp(-2ne?)de= (476) Forthe cach =0,5€02N bl >>, exo(2N\2) dr ' 1 = {osoeriie) ae = Trey) am Forthe case h= 15> 0,203 1 1(.0)=fom[2na(?~25) a = exp(-2ns)fexof2ns(s—1F] ae oo as e entanifen[emc}ea = ars aForthe case k= 1,20, Ne] >>, exp(2nff exr(-2a1 exo(2Mi)fex(-2m") ae ro) 4m) Inveting (476) to (479) in (4:74) gives Por the respective cae, which it villbe uf t collect ineoa table by way of complering the present chapte. ‘Tle 4.1 Probes of ng and of the Exaneson ofa Mane Gene (2N|s1 >> 1) |e Baan 1 aie a 2hlexp(-2Ni9)_|1~26lexp(-209) (2M) | 1-H exp (20M) ‘Case af talanced polymorphisms in which gene neither fxes noe becomes extinct are excluded re. Fom Chapter 3, these ae cases with £>0,h>1 or akematively, 0,40. Chapter) Socialogical Consequences Deleterious Mutation Presst Detonation with i] << wee shown in these pret naling of Chop ave wo unwelme conse bf hich a it the : sonal motel sued in he at ect (One thre fines ioc fit explora whole pcs bow ha ofan tly omogeno eplien whee 2 the sverige number of mutations oacuting perSeeenteetre seeteeen individual per generation. The othe to praluce slow erosion of a pecs fiom che ital stndaal of referees, ata rae that dependent on the population N. For NV > 10 the rte i slower than in the singe parene-o ‘fring model, but or sll populations, erosion etic. theft pat ofthis chapter [wil eaablh these results mathemati the second hal Twill cus certain oftheir consequences excl for human epultions ‘Amor fraction of deleterious mttions involve the cancelation of a patve property of some gene rather than in casing some entity new propery of devastating comequence to arte. The protein to which the rmuated gene gives expresion becomes a da it sit sound doing nothing ‘sf iestead of ciel falling proper fnctin. In sucha station here willbe no bd fie provid the dd protein ished aside, and so long as che comesponuing gene on the altemative set of chromosomes i in ‘working order and prove the sipply of the correct protein fom the working gene is much as nese Forsach adeleteros mutation A, the Inererorygotes inthe population possessing ony ane A fel no il ff rm i bocase the bad is shied by the good a Tt sony the unfornate members ofthe population who happen ta have om bo chromocme es ‘tha fel is il fect. Sach a situation is epresented bythe cass <0, k= 0, ‘which [conser fist. We can contemplate that in sch a tution might the quite lage, even of onder unity, becae if an exential protein were [knocked cur on both ehromesome es, the consequences ould be src ebltating, perhaps even lethal Since the ali to thi stage ae Been only fr fe] <1, however, twill be convenient to keep js] <1 forthe moment, eturing tothe possibility | = 1 ata ae stage of the discussion. Lecelshdsbe te proeblity hat the frequency of les betel x + deat tine & The chance of an inliidhal at random being of the ‘unfortunate homoxypous ype (A, A is jrotna : 1) the population being sampled at time & With many possible deleterious rmutacions A, all taken t have the same alvene selective factor # = 0, ‘occuring a ate 2 pr single et of aomosomes per generation (ue, et of eee re ‘gsmete) dhe etal number of mutations aking over along cme interval of ‘T generations in afxed population of NV individuals 24NT. An individ thom within te interval as a chance gven by the tne average of (1) of beng hemosygoue with respect o any one ofthe 2ANT murations Fea fooe . 62) the time integral in (5.2) being over the whole ineral T, which i say fromthe moment of accurrence ofa mutaion tothe moment oft extinc- tion. This tite nega jst the fancion that inthe previo chapter was called us) so chat (5.2) 8 duwreae 6) “Thisisthe chance of the individual in question posessing any one of the 2ANT mutations in homosygos orm, Hence the numberof tations with respect to which the individual incurs a sclective penalty & given by ‘multiplying (53) by 22NT, vz. DAN[uG)tde Ga) Independent fT Since uttons ate injected at x= = UN, wich very sal or N age encagh, dhe par af (5.4) for 0x mi meplible, Hence toevluate (54 wees the form f(s) caine nthe previous chapece foes) <5 For the present case h= Oy this was 6 NA 5 een farm 163) Han) so sfcient accurncy, where aMathematics « bovation Sls O)= foxe(-2N0a4) ee = 6a fle) Joo(-2m) je 6 eo (ami?) Jesofami’ a a3) fean(emte) ac ‘ (5.8) Hd Counting in the mutation rate 2 only those miscopying for which Ns] >> 1,13) neslbleunles + X The explicit path (0) followed by porccuar mation seas at x= x = WAN, «= 6 Due 00 stochastic fects the path wander around for a umber of generations without x exceeding“, unl evenusly at some time 1 () = O and the Toutation is then extinee, We can ak how lange the ie dference = ean te before entintion occur the hagest time differences occuring for ‘tations where stochatc Factions happen to increase xt ont % Tn the majority of cases where deleterious mutations become extinct ‘without incesing to onde their behaiout is conolle by stchastis not y election, with the probity of going ina generation rom frequency to a frequency in the range x to 3° + de given by the infinitesimal repesitor W _ Mea le | ox hh embed ey nl Ee oan om63) + 624) ‘we can sy thatthe gene fequency shifts in 2 generation fram x either x4 corto x— Ac with equal probability ‘The situation islike acne dimensional dfsion peoblm with mean free tht chat depuis onthe square root of the difsion dscnce x Anal Aision problems, dhe number of sep, hat i, penertions, required forthe Aiesion distance to change fom x to ether eo or 2x8 {gj - 625) Hence the circulation time of deleterious mutation i ofthe onder of 4 times the ages fequency eached along the pach x0) which the mation happens to follow. The Inger x that can happen beau of adverse select 4s -¥ wth F given by (5.18) or (5.19) according to the value of b. The ‘maximum creation times in generations are therefore shit his not smal ii 629 For BN 10%, b= 10% the maximum ciation in 10 gents frre tats ony 10 preston doin tne cept in sal plan pounce mich hee sot Shan dene “Acimlcet tide othe xr pA fark =, cr p24 kath not spec wud eo ca he anal th pet tfc dhs ac ve cated tow aly pe ne of population, and tha no actual rs of fines can arse bucase by the ime flfcts have arisen, the iil population no Longer exists. rowed the ‘sketrcan mutations have <1 eis largely te Every nial afer ‘cme interval fonder (526) bas ether 2 recessive des oe 24 {1 minane defects, with selection ony bearing down on fatuations in these numbers flatsations which are of oder (|). For [| = 01, A= 03 GAIL 25 and (1 ~ |) #095, s0 that selective penalties on the les foranate of the community are ony about 5 percent. Ii this selective penalty that prevents continuing mutations fom making the sination Drogresively wore. This for mutations chat sty IN] >> 1 which was sumed throushout che above dscason. The complaene view that sich ents are noe very onerous on the dsadantaged. If dhe most sped Frum ean run a mule i 4 mines, to be 5 percent wor at 4 minutes TO second should not be #00 mich of andlcap to bear. And to have & 5 percent les chance than the average of leaving surviving descendants veoukd not be flea grievous buen by most humans either. But there ‘nother darker sie othe mate impli inthe mathematics, “The frequent mutations thar ast ender ones seriously dev, while posibly crying litle penal in etersyete are likely for inporan ees to impose a grave penalty om bomosygous individuals Raving both genes Aefetve on both chrome ses Wath such a sation lethal or neat lethal especialy for ceatares in the wk without the technological support ‘which humans enjoy nowadays, 3-1. The average number of sch seriously eletrious defects would stil eA /s pe inva, wi Aas heer of tccurtence pet gts f continued tobe -0.3 we woud thus have about tne individual in thes aficted by an essentially lethal genetic defect. 1a ‘uch a sitwation the entre loud of maintaining the genetic integrity ofthe Species falls on the unfrenage ove iediviual in thre, station that in, the human cave a lest cannot he contemplated lhl. Allee work of Chapter 4, which the derivation of 610) depended, appeiel tit ight to be based on | &< 1,50 tae we have to reexamine the premises of Chater 4 belore accepting the plications jst mentioned Reference back wll show chat thre apeomimacons involving x=2)fx+A(1—20) cA Tees[xr2h(0-3)) ofvere made. The fit watt replice the denominator of (5.27 by uni, For > 1. Reference to Table 41 shows that minor ‘mutations with 2N | £1 have a protaility of penetrating a species not much diferent from 1?2N, the probably for penedaion by a neural mutation. Write forthe rte per generation per chromosome set at which ‘mutations with 2NJs| < 1 arise, Then the total number cccutng per senertion inthe whole population is2NE. of which become fixed. Hence in G generations £0 such mutations Become fixed, so that the species sci a steady growing penalty wre (- 2)" 2 ea). 60 Ww the mains for which is determined having 2N = Mf sialy 0.2 we rte £ = 03, then for a population of 5+ 10 individuals here is a signieant decline in G = 2NIE~3 +10 generations, which for atypical mammalian species is about 10° years, signiicandy less than majoe ‘evolutionary time sakes of several hundred milion years. Hence fi Ihgh 03, species wth population numbers not exceeding 10 ust either collapse on sich tne sles die to a erstent erosion of their genetic ‘material cr new unerodes genetic material must be agi i cme wa In relation tothe dicusion of the next evo chaptes, the ater a interesting posi Ie would explain why so much of DNA goes unused, Unexpresed [DNA cou he old eroded genetic material that has been discarded a new material as been aquited. The exces of unused over wed DNA, arto of Be peihaps 20 to 30 w 1, woud then be # mean ofthe antiquity ofthe rolrnary proces fete Later beg -20 + 2N/6, a hundred milion (generations for IN 210%, £03, Reruming to much shorter fie sales, humans need no encouragement | a all to form themselves nto seal snbeed groups. Alou instints sen Girected coward prohcing an immense fragmentation of che total human fopultion The typical ze fined groups, whether the hunting groups [Neolithic human, che medieval wile, the more moder ee o lan, oF an arocracy, i about 590 penans. So too are scientific academies and Ihoues of parliament. Given half a chance this is whae humsn psychology lays een to favour—astntion that is clubbable, Allowing or uveiles ‘who do noe survive ro marae rouge with etal of about 500 would have had an efsctve vale of N around 200. So long s man’s penchant for subdivision was supported by adequate geographical syarations, well and good, nothing very violent could happen. But aia subdivision due to Iba oer, ota in medical times due ro politcal fat, must soner or later become explosively unetble, s soon as some perturbation of society causes veal eoncigus abgroups to intermingle. Inability arises because the progeny of pacts from dierent subgroups woul be fe of homaygons Aebltating receives, since the adverse mutations posesed by one parent ‘would tly f not wholly be diferent fom those ofthe other paren. The Sutcome would be a generation of fr more competitive individuals, with the Tikehod thie geographical expansion woud take pice, sucking in more fand mee subgroups into the mixing po, thereby generating a kind of dltonation wave. that would exhaust itself only when impassable roeaphlcal boundaries were reached. ‘Many examples come to mind, of hich the almost instantaneous bre sp of medieval Europe at the end of the fifteenth century is excellently documented, The medieval population was lngely rural, with severe legal restraints imposed agains the fice movement of people The longer the fabgroupe in the villages were fribly kepc apart the more unstable the Sinsation became, with ts dénouement in Briain coming with the los ofthe Trench posestons and the ensuing War of the Roses. The resting biological explosion was that we asc nosalgically wth Shakespeare sand Tar England “There must be fow people who ae not fascinated in some degree by history In their detication to getting the fess of history as eomect 8 aprosible—no eat takin view af the inal age who stem oly che twaters—hisorlans serve a crucial function in sccety. Our lives se ‘operenced subjectively Igy as events tha are past The notion that We live "in the presen” tan ills, fr na comer do we experince an event than i pa aleady Asa mthematictn might pu i he present” bar reise sro. No wander then hie iti portane to have the past at comet at posible. Even 5, ite of the goat asenation of ial, T never had strong impulse to sty history profesional, or dy a it were essenially becmse 1 ele char historical sedis raised a whole le of ‘overeing questions which were not anwered ina stiictory way simply could not believe that ic all boil down eo polices formulated by the individual ues of communities who pop up and down throughout che pages of history like a craupe of jack in-a-boes Tegan tel bere abou it when came to nese history in read of the development of technology. The march af technology seams always 10 hhaveboen forward unlike nations which lowich fora while and then decline Bar technology could not be everything. Ir did nc explain why dhe Hellenistic Gaels, who had been so dominant in dhe days of Alexa, came to be subjugtad couple of cours lane by dhe Rmans. No aw it ame about ‘hain the thieenh cennury the Monge were suddenly able to explode cut of Asta and svecp all opponents before them. Suc convulsions fal esl nto line, however, when the bilogial considerations ofthe present chapter ate Trough wo bear The Hellenistic Grecks expanded inthe Medteranean by sublching seztonleing colonies cha dil nor epand much io thei Fhnwerlands, and which therefore became Lagely closed communities, each mating perstently among is own inhalants and so incusng the genetic penal deserted above, The Romans, onthe ether and, emery een a Foie incerminglng of thes, developed an extensive hineland, la ens the cyclic proces ofinreeding and oueeding the Greks and Romasseem tw have been at opposite phases, the oe incuing bola peal, the ‘othe inthe expansive proces of bein ied fom them. eis remarkable that our subjective preference for what cems desirable in| Ie and what scems casos should sn 0 exactly counter othe biologie ‘tuation. Our preernce & overhmingly for a eure Ie, suru bp frends and thei ful, of whom we woul hardly numer move than 8 couple of hundeed, Daughters and srs almost ineicably ausry within che lub, seeking ro preserve material posesons and common cultural vas of Comfortable an ex in contest ta population upheavals fllowing defeat in vr in conte ro gate gusting their home communities in srw dato poverty ors oueasts de to nonconformity ver sme ise or ote. Ye is the migrants who are eaveling toward a fue in which, by genetic mixing, ‘heir progeny wil cme to dominate che wold. “The biological problem ionicaly becomes more acute the higher the social cls forthe higher the clas and the weather ts member the more they are able to indulge their anubological preferences. Patculsly ‘vulnerable in times gone by have Been royal households. Although fee to decide their mating parmer, kings and princes oped overwbelmingly for brides who contbuted posesions an inuence thereby Tmitingchokes 0 an i-group eypialy ofthe order ofa hundred, and so with mathematical Cetaintyenwuring degradation on a ume scale of a century or two. There Ihave been exceptions with notable results, as wich Robert of Normandy’ infisution for Hlerleva the bare’ daughter, from which frownedon Tiskon came William the Conqueror Willan himself did not perceive the biological leson, however and within @ century the Tne of his immediate descendants ran out. Thereafter the Panagenet house had a comparatively Tong un for its genes, fom che mil-welth cencry to the death of Richard Iban 1465. The Tudors hen managed a century anda half the Stars a ‘entry time spans inevitably dictate by cur formula (5.26) Modem populations are 30 large, with N usally excesing 10° and semetimes even 10% that one might dhink populations tay must inevitably fe living in a favoursble period of almost tal outbreeding, Yet howe opulations with bisoris of mmigane lows ke Austaia and the United Sats and those which rent have en grit tirel in the fermath of ver like Germany and Japan re perforin so well n comparison with les nixed populations ike the Brith that [have to sect that some ofthe frnetic effets of inbreeding ail nger on in the oor more static epultins A glance eric flows on Bash motorways does nx sues ati situation of course, bur he iensediiculy which the British have in ‘hanging houses betwen one pce and another sues population tha sil eather gly rote in ts oes, isclnmes manner of speech, adits ‘habs and pubs. The Bish population incerta ac ineedin anything ike ‘medieval sens, bu ce argos in spt ane comerce are fine tha ‘ natcn ony sds to be ile subpar geneialy for the eft to become rather obvious feNeo-Darwinian Theory We A sexual system of reproduction with cro eee commonly supped ro be in neo Darwiniantheory the penalty being that mas small advantages ae lost hy stochastic cffets, only fraction“ scceed in penetrating species. But this penalty rust be pad, slaceotherwie species could not evolve a al ina positive ‘When a species is developing new puters of behavior advaneagsos changes must neces be smal, ease the genetic material ofthe species ‘nner anticipate what anew pate of behavior i ing ta be in alvance of cheng adopecd—the species must ede by slow degrees toward what ‘se Bu in situnton where a species aapting eo an environment it his experienced before the sation could conceivably be otherwise. Genes ay Ihave changed over an intervening period since the envionment wa as encountered bt provided the intervening period was not to long by only 3 few tase pir changes on the DNA Sach comparatively nino changes may be revere, hecase ofthe species being alteady a the verge of what fenetcally required for readapation to the old environment. Larse ukvantageos changes rough abou by as Lie ta single hasepair change fn the DNA are then conecivale Such cates ate noe evidence, however tha advantageous changes an e ge when adaptation with spect on tate new environment isin question. Finding the ne-Darwinian theory to work only wea in che general situation, sy inipresion is that some evolonies have wight to sped things up by wrongly conser canes where species ae only coping with envirnmental conditions they have experienced before, o that memory ise misinterpreted as cover. “The peppered moth, Bion tus, x0 called becuse it has speckled ack ana white wings, Roques misinterpreted in his ene. A dak form ‘ofthe moth was fine noid ner Manchester inthe kd-nineteeth entry. “They yeas lane it ad carne the light fm of de mod, which bad hitherto been more commen, ax much oa hundkedfld in the aes. The ‘explanation offre fr this phenomenon wx that the dak ar of de ech ‘wes nt as conspicuous wo inl predators the light moth gine tees which ‘were blackenedby the soot fom the buringofcal ina heavily polluted nea, The dark frm of moth has a working gene which prices he psent ‘melanin, a gone that has bose inoperative in light-coloured moths, For convenience of dustin, suppose selective properties to be so severe that a juvenile moth bom lghe cannot survive to maturity i an environment of at tres, and shat a juvenile bom dick cannes survive in an enim flight ees. Now suppose he enonment ool, ie with dark ees, Be then with light, and so ony the svitches taking place dough phases of ‘ever years in which both light and dak res are present, Wht harps? ‘Star inthe envionment of dark tee with all melanin-prodeing genes inworknyondee The rate at which the genes Fecome inoperative is-10® pet ‘mete, so that fora population of M juvenile mots about 2+ 10d genes be injected into the population at each geoeration. The dud gene Hing recesive (theca h =O severely deleterious effect shows up only in Fomarygus juveniles of which dete are Ma, where «5 the frequency of dal genes Hence with the effct lethal in chose homozygous inva "TMs dd genes are siminatd in cach generation. Seting ths elimination ‘equal to the injection rate pes x= 10°, so chat for M = 10" san example tour 100 moths are hor light in each generation, despite the property being lethal in the environment of dar res. Permitting theo population of most dark ms to survive for several generations asa switch ade, now kt the dak wees give pace to light es, “Although the okt populition with a frequency IO of inactive genes can ‘prvhce only one light ma milion, the ceumsance that on immense fhunber of juveniles is produced tans that some light moths continue Be thom, even though av dhe tees become light, avian predators produce 8 spectacular decline ofthe al population of dark moths. With da-cloured jiwenies Feng picked of tas on thei way toward mur, the hight ‘moths come through t ay in fr greater propoton than the ratio of ‘one 1 2 milion in which they are born Selection agains. dak moths taining marty eventually Becomes intense enough forthe light ones to find each other, an forming to tke place between them. Whin this happens there isan explosive production of ight-coloured juveniles, wth she consequence thatthe fsquencyxof the inetve gene rises with reat apy fom its former vate -10° to unity Notice tha isthe capac faults to produce many aves that saves the da fr the moths If als produced tly afew juveniles lighe moths would hardly be bom acl asthe population of dar moths ll and the ight moths would never find each other, and the sees would Eecome extinct. From this example we see, therefore, Inhy creres exposed to date ccltions of the envionment necd to Drnlae immense number of juverles—in order that rare properties {tinue to show themselves 2s the population falls ‘Now consier a witch back from ight wo dark ees, again permiting 8 umber of generation ofthe moths to aceu during the inervl in which thesoitch 6 made. Fo survival ov es essential so raat the melanin ‘rovducing gene, and wo doso before de sch ofthe ees completed. The ‘moth has two avantages on its ie. Provided dhe tres ave not bee light (eae) oy Pating A= 109 fr sina wth a lage numberof posi of impovenent, and tang N= 104+ = G001, (73) gives @ > 500 feertons The yncaton lng nthe human cs abot 20 yen tare tine seer dgeant human inprotenen wal te ol yes an inate tha sonoma with fat evolution fr cur ei, Such {thing ut eninge However onthe exten ope aber si pou of npeovenen, and thacoe on evens cating ach tae of poms which oso see rm ating nd Shing he pons valle ta peie Retuming now to the poem of whether hese of juveniles is ‘adequate to permit evolution at the rate implied by (7.2) and (7.3), the next Sep orevock the anaes lowing 312), bu ith > 0, = rand selacing 2 by, the sim bring 9 obin the verge rab of Sates maton pone ype id place (513) enon hoe safuteynas a “where the appropriate expression frp) i ine ee eens exp(2Nes xa) Again taking 2Ns > 1, we have Ho Zesp(anss) = 2 6) foes) = IAN, s<« From (74) and (7.6) we see that the average number say of edvantageous mutations poses by an individual is = AN a3) With N= 10% sane = 103 per gamete asthe favourable mutation rte ina cae where # very lange number ~10° opportunites for improvement ‘xi, have f= 890. Hence each indvial posses many fvoumble rmtations in sich a situation. Selection takes place because of statistical attr inthe dstibuion of favourable mutations, thowe with + ("mutations having 2 selective advantage (P™ = exo(2ius) a3) over nv wih (4)! mutations. The equrement chat the supply of expendable juveniles be adequate to maintain the evlution rate i that the exponent of this exponential sould nor be greater than of order sn, Des < a) aWith (72) for wwe therefore require S2ANe s 10) This i inorder chat significant evolution may occur in @27Ne generations. Ifthe supply of juveniles i such that the upper Timic imposed by (7.10) satained, evolution ean improve the fines of 2 species bya fctre in only 16 generations very fast at; indeed rate 5 fast chat the limiting fectce om the sped of evolution is seen to be the silbility of adrantageon mitations, not the genetic et of ewoiton. Give sient aval, evoition can proceed at rate which by any resonable praca eonsidention i extremely rapid. The station appears cleavent and the circumstance that some genetcits have conciled ‘other ates something of a mystery especielly aa whole new shoo! of ‘mathematical biologists have wed thie to question the correctness of the Darwinian theory sel, referring instead what has become known 8 cvolotion by neural dit (or example, M. Kimara, The Neral They of Maleculr Evlion, Cambridge University Pres, 1984). Quite apa from the impossibility of arriving at such proteins as histone by random rmtation—that andor tals—the above considerations show that ‘opportunity not the speed of evolution which isthe problem for the Darwinian theory, the problem i the one emphasised alway in Chapter 6, that opportunities are confined to the which can be reached by only ingle taser changes on the DNA. ‘On pages 26 and 30 of his hook, Kimura states chat for evolution proceeding at such arate that one new gene with $ = 001i subsiuted Hyoughout a species in 100 generations, che cose is so grea chat “no ‘mammalian species could oleate it, whl for one new gene substiuted every to generations each patent mus eave e = 3.27% 10 ofspeng for one of the ofpring to survive apd reproduce” Accoeling to the above Ascusion a faction sof the AN advantageous tuations arising in each terneration kecome fied: Thus fr one new gene to be sbstiuted in two tenerations me requte 2ANS = 0.5, in which ease the genetic cot factor (7.8) is explo) Since Kimura defines is lection conicient to be al of urs, a value 0.01 in his statement comesponds hereto 8 = O02, and expo!" = 2, Such a genetic cost ijt within the selective capacity ofa ~ population with 2N juveniles aval, che cae considered above fr bins the langer mammals, For the ub of one gene wit += 0.2 nto fenerations, only afew juveniles ned he born for each surviving adult mumensedtcrence fom the 3.27 = 10 avers which Kimura claimsto be rece The discrepancy indeed so enormous that it seemed necesary to stem to wace ts source, ‘The attempt proved a frstating hisines. Tostart wich, Kimura gives no explanations only atements, an then only on pages 26 an 30 of is book. Tescermed to me curios that, with 250 pages avaable, a clearer account of wy the Darwinian theory wat as devastatiagly wrong asi is said to be holds have been given. A carefully eeasoned argument, at whatever Tength was necewary, would have been worthwhile in esablshing 50 profcind a res. In Fhe I also fund nodhing. In Sewell Wright’ age treatise [foun four page (op. ci, Vl. 3, pp. 434-437). What was this I ‘wondered, ony for pages out of 2000 devoced othe dsproaf of Darwinism, and incomprehenshle at that “The concepts cm which Kimura huss his statements sem to have fst sven in s paper of LBS. Haldane (Jownal of Ges, 1057, Vol. 55, pp SII-524),a paper which ound just as euous asthe more recent apts ofthe sory. Embed in symbols, whose meanings were a fist unclear, Haldane makes statement that & both uneglvocal and checkabl: ‘The unit of evolution, the substitution of one [frm of gel by nother, if arried out by natural selection based on juvenile deaths, wu involve numberof deaths equal to about 10029 times the number in a generation, and perhaps rarely being 100 times this namber ‘Let us examine thi statement fom two points of sew Fit comet pin of view fom which it at be sen ob utr, a second, sane Incerpretation on which ic ssems to have ben based. Wate x) for the frequency at tne ¢ ofan advantageous mutation with initial fequency Provide the selection factors is smal compare to iy (as iis taken to Be {in Haldane’ paper), tis ielevant whether the ratios af the ness of (AA): A0) (aa)ae ken forthe cash = wo be Deesd steel aay Lsl-Yestnae ay since to chefs onder ins dhe foe (7.11) canbe changed to (7.12) simply by absorbing a factor 1 ++ int the normalization coefcient cz For cone formity with eater calculations it would be better to we (711), butt permit easier comparison with Haldane and with Sewell Wright (ls it), (7.12) will now be wsed. The sormalation coefcient efor 9 popultion ‘which remains constant from generation to generation is then determined by [x +2x(1-2)(1-45)+(1-2)'-5) + (713) atl, ts cay andthe change of fm one genet tthe nex gen by Ax+g)-aleesret-ot-d9) cas ai me ‘the uni of me being the generation interel ae ee re Inthe absence ofthe slave factor seach juvenile of whatever genedc type woul on the average have the same chance of surviving to reproductive ‘oe But in che presence ofthe elective factor juveniles of type (A, AD ave ‘chance increased by eof surviving to repeedactive age, while heeroyantes (Ava) have a chance ineremed by (1 ~ Y's) and homexygotes by atl =). ence the gin of survivors by type (A,AD is 2(q -1) = 2820-3) wea) = BED on hein by here 2ni(t-s)far(1—ts)—1] = 28-29 rts he pi by moat Se to Nala dat] = — Baeah ca) The sm (7.17), (7.18), a (719) of ane 0m hich saasetcrsas739) #), Bue with 3 severheless smal compared to unity, stochatc fects da noe affect the rest signticanty. Sach i seems to me i the standing concep of maturl ‘election, whereby the constant on the permisible numberof individuals forces genetic change in a species. Hence, sconding to the standard concepts, the number of genetic deaths required tof «gene (over -+! ssrcatons) is clove to the population number N, nota comparsively lage rip of In practice, the assumption in the above calculation that N remains coment from generation t9 generation is unlikely to be sty comect, cause asa species improves is adaptation to the envionment, competing species tend to be crowded out, thereby permiting N to increase, More sity N shoud he considered ae a fincion of x. Before proceeding therefore necessity £0 consider whether the result (7-21) could be sieiicary change by allowing N to increase with x. Suppose che ginal ene type 4 go sustain population No, and let the population Be Ns fs) svhen the fequency ofA has en to i place of (713) we then have a fai? satay 4940-95] a. ‘where on the et we have the preston of afing by the generation in Uwhich the gene fequency is and on the right we have dhe function f compu for the next generation. Ths dln, 733) In place of 7.15) wea hve ey, de eG erd) sho Hoa? +2s0-a)1 - (tated) Using (723), the fcr 1 +d fle ences (7.25) and [e-fea-n] aan et enone (726) @ 21s) Since (7.26) she ame 2 (7-16), permitting the population to vary with x hawto effec om the penetration oA. ‘We are now ina pesition to et ta the per of Haldane cited above, ‘Suppose thatthe gene type Ais deleterious up to time ¢ = ty at which the faequency of A is % <<, the population number being No. AC! = fy a8 cnvironmental change occurs which cures A to Become advantageous © thar thereafierthefequency xf A increases according to (7.26). Tilo supposed that atime t= the population experiences a downward ep frm nhl ie gully recover as A penetates the species, until che original population Nis retablabed a6 resto unity. Such 2 model can be ‘presented by choosingAa=t=s(l=x) an with the population fling at tie 1 from population number Nyt Noll = st ~ x] = Na( =). Thus the population when the frequen of ‘Ais xhas the vale Nyfle)= Nall—s=s)] (28) and the deficaf728) below what the population would have ben ifthere fad benno environmental shift is sNy(l-x) (729) ‘The defice (7.29) fora single generation, while the cumlatve deficit ‘over the generations thar elapse butween the enviromental change at = and che recovery ofthe population to Nyt x= Lis given by ay E-bay f-ne SN g[-2l-s)énxy+21-m)] 5 (730) where (7.26) has beens for dl. Omitsing the small resin thi Haldane’ result. Sewell Wright, on page 435 of is volame 3, cludes the terms ins Putting 9 = 10 asa example the coeien is abou 14 and this ithe source ofthe atemene that atl selection fra favourable gene “wally involves 2 number of deaths equal wo about 10 or 20 tines the number ina generation..." The deaths however, have nothing o do with the cso ing a favourable mutation The desths ave en cased by the evionmental change, and are arbiar at that fori (2.27) were writen —< sa=1-S0-3) . S¥s aay the numberof deaths woul be a factor Ss mes (730) Hence (7.30) i a arf ofthe psc enviromental effec assed in (7.27)- One could ave wth move sense thatthe penetration of species by an avancageous eve permits the population to se, say according to f)alesx a3) “Then extra ves are lived, with a cumulative total daring the fing ofthe favourble gene om, snp 2s | SD a3) “Te incegral ere is lgarithmialy divergent at x= 1, because in the absence of wochastic elec the favourable gene never penedates completely —s We ‘aw from the outset in Chapter 1. Taking stchastis to fix the gene when = testo =, che lives gained number (734) “The tation is videmly so abitay as toe genetically irleant. What enctially relevant sche result (7.21), representing the number of wenete deaths which ocur inthe fxng of favourable gene agaist fed constraint fon the population, and hiss the wy thatthe operation of aura election {swullypesneed, Haldane so-called cost peineipl san hon. of“The reader may wonder if could have misinterpetsd the station. [ think no, for thew reasons. AS aleady mentioned, (7-3) isn ro ae formula given by Sewell Wright, not ui che msi term -2 En bt alo in the ler ces involving Second, in the introductory rear to his rarer Haldane writes explicitly of enviromental decline being eased by “olin by semoke, a change of climate, the intrdction of « new fod source, predator, or pathogen, ad above all migation to a new habitat.” ‘And thin i logically sensible explanation of (750) exited, Haldane faper would have been writer more clely dit wis, Sewell Wright ‘would have explained (7.30) instead of conjuring ike rabbi out of hat and Kimura would not have se his book metelyon the obscure remarks quoced above. He would surely have devoted whole chapeer at lee 0 & cael analysis ofthe preci argament itl, “Toend thi chapter let us sce if we can lst understand the statement each parent must leave e¥ = 3.27 10 offpring for ane ofthe ofprng to survive and sepoxtace.” This satement was contingent oa one new gene being subsite throughout x species in wo generations, ‘Suppose at time = Om et of fivourable mations all with the same selective ctr, have frequencies By 2 POL no (735) (Using (7.26) for each of the genes, considered to become fixed independondly fea oer the mes fy fixing are deernined by 736) For one gene to become ft every evo generations we mus have , a a3) From (736) and (7.37) i is easy to see thatthe values of yay = are ‘nary spaced both at small and when i clove to unity. The lat, -& eee eee teres area rising fom the 1/1 ~ xterm in the snegeand of (7.36), can be omit Ihomever, because advanageous genes become quickly Sued by stochastic Auctations when their Frequencies precach unity. Hence, in pretce there woul be no lage number of genes with x values per unity. Bu those with "small at til e narowiy spaced, wih x, vals determined by ie? Je (738) in the absence of thas fet, which can be neglected provided x, > rom (7.37) and (738), (739) LS natin (740) in oder that one of them bacon ie every two generations. If now cach fumble gene is accompanied by an environmental 10¢to 10 take contra of the sisation, determining the knees ofthe changeable amino acs in cytochrome cin. Evolution thete may Ihave Been, but memories of evolution are masked by selective neces Phylogenetic tes for proteins such. eytochramee ar nel uns the ‘arable amino acids wed for cnseuctig the tes det etal to within 10 t9 105 in the sleson factor for manna ant even finer margins Ke species with very lage popultions—invenebrates and plane. This would imply thar mst amino ak of ensync chains do not mate, an exceedingly sly supposition in view ofthe mandatory character ofthe ret of the amino acids. To argue that while a fsten of amino ae tes are crcl the Be frccon ranging fm about) orcyochrome-cessentall to I for histone to the exent tha they cannot be varied at al, while the rest ca be vad freely without selective advantage or penalty appeas gute untexcoable Besides which, there are tee further objections, ane a reduc a wad, another a flaw of logic, andthe tied a disproot by postive fs, thar rule protein phylogenies ofr out of eour chat one must wonder atthe state of eonfison which ed othem everbeing considered tall Suppoe we aecepe that 65 amino ace of eytochrome- ean drift without selective ontol Thet (82) eo (88) lead inferenialy tothe flowing schematic ‘rlutonary picture in which time considered to vance inthe sense ‘hon bythe aow, with evolution causing branching to occurs ato ed tat the present moment othe groups (a), (gh Proent aw ww eo ow Sn “The ordering ofthe branching in the shee taken with the hypothesis «fandom drift for 65 ofthe amino ai ofeyocome-c, requires tha 2), the ist soup to pee aay fom the ethers, shall show the greatest umber of amino seid ferences fom the ther geups. Omitng (2, () wll den ‘how the greatest he fdiferences, and son inthe same order asthe decreasing numbers on the righthand sides of (8.2) to (88). ‘What this view of events does nor explain, however, is why the Alerencesbeewsen (a) and), () (shoul alle esentaly the same, toy the dferencesberwce (4) and (c), (8 should ll be esenealy the same, and so on. Aditonlly for this, we woul have to asume that random dif ofthe variable amino acids hos cccurzed ac dhe sme absote tine rate for ll he species of 6), () (4. Then i will oe mater which Species fom (bey h) we ene, ts ta of amino acid dferene ro, cf}(c) will be the same v0 within stiical ications. Similarly for the diference between (6) and any species taken fom (c,h. And 0 0m, through the sequence (8.2) ro (8.8). Bu the wouble fr this interpretation of (62) 10 (8B) is that mations occur with tespees to generations, and senerations donot relate uniquely to ime, Among mamas there f mote ‘than atenfeli difrence of generation interval benwcen ce and akin the one hand and hoses and shrnp on the ober. Variations of generation Tength can be as much sa hundred among nsec, while yeast nd ve other fungi have generation lengths which are minute compared with most other species. Yee the constanr diferenes in (82) to (88) hold good to margins of w litle as 10 percent foe the lager numbers and to about 20 percent forthe smaller numbes, an impos for even twolOd ce ‘hreefold variations in generation intervals, which are common. This isa reduc adabsuum so evident thar proein phylogenies ould suey have teen instal dismised on this ground alone. Posibly wore sil protein ablogene ack proper causal, Mutations between branchings are asumed r have syed the way they were a the moment they eccurted.A mutation that cum, for example, daring the time intervals beeween the branching of (c) and (2, i asumed to be posse by al species ind) (), 8). Bat the amino ack in question ay have changed agin fr some ofthe species i (d,(), (h, changing lesen ways for different specs. When numbers of mations ae fe compared tothe numberof changeable asin ai this ection woul act he srious ie would be a second-order effect. But for cytochrome-, where ‘esentialy all amino acid thar ave chargeable have been changed in one species or another, multiple mutation atthe same amino seid site are not necessary of second ont “The only dra aeilable for constucting a phylogenetic rear of couse the variations found in present-day species. Even f there has ben a tee of the asumed type, presently data ate insuicient to seconstroct te This s ‘wll ecognised, an what i usally done inorder to obtain nique tee to choose che branches and the numbers of mutations sociated with them by a minimum erterion of some kind. What doesnot seem tbe 0 wel ecgnized is that cause of repeated mutations the method val when wed, asin the ase of eyoehwome-, over lng time itera, The rial sinaton, if ie exited, is iecoverble, je as sytem of diferent ‘station sno ole when the oundary conditions are incomplete ote eee “The hid objection & straightforward practical. Hemoglbin consists of four copies ofthe hem group of about 2 hundred atoms, fearing iron ‘rominently, eld in a terahoal-ike smcrre by four chains of amino ids Fee our chains in mammal, to consis of echeroglcin wth 14 Sino aide and two of hemoglobin with 146 amino acids. Both the cand B forms have existed throughout che evalsion of mammal and, phylo- fenetic tre could validly be constructed fom the amino acid chains of Proteins, one should evidently obain an indirect te fom the & and forms, With the same tee, and with mutations ocouing tan assumed constant rte sith respect to te, amino aid diferences herween one ‘mammal and another shoul be the same to within normalization ator of fonder unity for ehemaylbla a fo eon Te 8 Marrs Showing Differences Beween Mammalian Species for Heim eo (G) =O Oec \w) a i f F lo : 2 wwe x x x GIGeee Bar thet no normalisation facto fonder wit shat brings the numbers shoven in the table on page 133 into consonance with each other. These ‘umes are a direct and obvious dpreo of the whole omeept of protein pylogenics Although phylogenies wing proteins have beer tainly fentured and emphasised in evolutionary literature, pylogenies using DNA are Inctesingl being investigate. Sach phylogenies ae open t jus the same crtclans If hey inch hae pais thar can he of welctvewlevance. Pt variations contingent on the redundancy of the genetic code should scinely say the pola of reutality and so be asaisfctory source of evoluonary dita. Resrdant DNA, not giving tse to expesed proteins may aso be expect to dif nesta slthough phylogenies exensing over Teng time intervals ae not secure even for edundant DNA, since DNA that ts present rednuane may not aways have been unused (hater©) Summary and Conclusi The proent nay has been concer wil crt he al wi he ef skeen okt muons oxeng one fad geet fees he clas - Devin nae Yoo ane le ll cechothet they when epee fom roc pom toe ema ay nn ode oa ablg mallee «can be no postive evolution. Rarersshrntagsus mutations are stamped by mor fequent deleterious muations “The bes that natural celecton can do subject wa specie environ ‘he hold the deleterious mutations in check: When the enlronmbent unt fed there a how genetic erosion, however, which natural selection cance prevent. To aul dis slow erosion, ganas like acters that propgate ssealy must spend lengthy periods n deep Inberation, king up an ‘naetve phase which may involve the production of spe. ucayorc organisms rpicaly passes sexual cycles at primitive levels and pease sexually a higher levels, Tether with che phenomenon of crosover, sexual cycles and sexual propastion uncouple mutations on Alferent genes. Provided ewo genes are or std close together an the same chromosome, mutations occuring to them ean be regded as hacoming uncoupled in afew tens of generations. ven genes ited adjacenly on the same chromosome separate in afew thousand generations, This ell uch shorter chan major evaluconary time scales. The imporant ect of uncoupling mutations is that natura selection can then promote mvantagcous changes as well as keeping the more frequent deleterious tations in check, 2 desiible reule tempered, however, by two considerations, With mutations uncoupled, natural selection cannot tara Fock deleterious mutations if they are very sland over along ime alge urbe f small dcadvantages escalate to a erious handicap Ths long-term inability of narra selection to preserve she integiy of genetic marr sets imi ots ful if, imi estimated in Chapter 5x be ome 10 to 10° generations. Over long pris species must ether sequire new undamaged fenetc material or decline occur. Redundant DNA may be an accumu- Toson of genetic material dat exceed this limit attest che pst and ‘which hae now become dca “The cond consideration of fundamental importance in a sexual tnd is that half the genes of rwo pares are discarded ina generally andom way acthe bint of every oping, ol ofthe dice situation that inevitably leads to stochatic effets which cause most small advantageous mutations to be lost. This Tos, perhaps suprisingly, doesnot prove a particularly serous Aiculey fee lasge populations an foe mations that do. not involve changing move than ane hase pir on the DNA ofa gene. Subjet to eh crucial condition, an advanrageous mutation can be discovered and redacoverdofen enough frit eventually to run the gauntlet of stochascs and fort to penetrate apd become fixed in a pci eee teaeee! or populations exceing 10 individuals among whom mating occurs at ransom, the imitation on positive evoltion eset by opportunity, not by the cow of seston a some investigators have maintained Opportunity ‘consists of improved adaptations to an envionment that an be achieved by ‘only single basepair change on the DN, Should two oe owe base-pait changes be requ before an advantage ean oceus, even lage populations fare unlikely to dscover Thus opportunity exists only when genetic aerial i alteady very clare to an improved state. Examples arise in fluctuating environments, becase «frm of gene tha is an advantage in ‘one envionment can become a dsalvantage in another. An environmental change can sometimes make ideale o knock a wocking gene out of ‘ction, and single sentive base-pair change may be suficient for this ‘hereby creating an opportnty of ecovery were the environment fo retur tots ogi state. An environmental oscilaton between light and dak ‘tees for the peppered moth was the example considered in Chapter 6 “The ability of species to adapt by changing one bse pai at atime on| any gene, and todo so with corparative apd if selective advantages ze resonaly lage, explains che fine deal ofthe matching of many specs to their envionment. twas rom dhe careful servation of sch matchings by naturalists in the mil-nietcenth century that the Darwinian theory ose Because the olervations were made with extreme cae, ¢ as highly probeble tht immediate inferences drawn from them woul prove (© be ‘comet, a the work of Chapters 3 to 6 shows toe the case, What was in fo way auaranteed by the evidence, however, was that evolutionary inferences coneety sade i the smal for pies and thee vats could be extrapolated to broder taxonomic categorie, 1 kingloms, divisions clase, an orders Yet this what dhe Darwinian theory di and it was by ting far outside its guaraneed range of validity thatthe dheory ran into ontroveres and difclies which have never heen cleared p over mone ‘hana ent "While i 6 good plan to stem to apy new ieas at widely as posible, dre were sever reasons fr misgivings even atthe outset o which ‘ore attention should have been pa The argument given a quater of 2 ‘century caler by Esward Blyth, an argument which really proved that species cannot aap cutie aly art its was side-tepped instead of being answered. There was alo the ificuly tha the fos econ did not support Dewi’ encepe of major changes as for instance from reptiles to Ga‘Matteasties » Evolution ‘mammal, being achieve by very any small tp. Ineresing discovers vere indeed mae in the fos recor, hut they only resented adaption of established orders, not che Inger connections wich should have ber there ithe theory were fully correct. The presenttion of coves to the public was heavily biased to emphasize the pro and hie the cons process ‘much de bythe founding in 1869 ofthe weekly sence magne Nase, a magirine which har always seen the presentation of the Daewinian theory fn dhe ment vourable light asa pamary objective. ‘The problem of speciation was neces dificult inthe nineteenth century. What ic tha permits roupofndviduals, which commonly we descnbe as forming a species, 10 mate succesflly gencration after ‘eneaton, while somewhat wider group of sil-smiar indichals cannot do so! We know today thar the two chromesome sets denoted in Chapter 2 by Pand M, which an individual obtains from i male and female parents respectively, must be suficinly alle for (2P, 2M) to be aeanged into ques, (2,2), tha can be matched with sufcenr acurcy fr cosover| followed by sucesive cll visions to eake place FP des by mote chan a small amount fom M, the complex proces of meiosis goes wrong. There ‘the very ajo dficulty fr evolution in the lage thatthe choos of widely separred taxonomic groups ate very diferene—repcles ae very Aferene fom mammals. So how did the chromosome structure of rete change ito tha of mammals If we say by internal mutations, many small steps would be needed, since a lange change of structure cccurtinginone step to one individual would be senile, bcaise it would be unmatched in individuals of che oposite sex. Indeed, any sch large change woul have sell probability in he fist lace, and the further chance ofa contemporary member of the opposite sx posesing jus the same interally generated lange change woud be mich smaller sil The consequent need to mulity minuscule probabilities rls out large spontaneous changes of chremoserne seucture leaving ony the alternative of very many small changes, Many changes should be eaceble in the fx recon, which they have not hes. “The concept discussed in Chapeer 6 ofan exteraaly incident genetic storm overcomes tis dics, because both the chromosome sets P and M se exposed tothe same external source of change. Both males and females are acted upon in the same way and although for any particular mating couple the chance of P and M being alered by external arack in an ‘avantageous way mye small, the smal chance i nat squire Given & ae sufficient number of couples én lage enough population and an ‘xivantageous change will happen sooner or later, especially as genetic ‘tornsprbebly continue fr “10° generations. Hence the total number of Couples exposed to change i -10'N, a large number, permitting even Very nly sltertions vo P and M to happen, should they lead to a viable ‘oteanien. Large changes to P and M separate the ofpeing of a mating Couple insaely from their ancestral cock, and f several sch changes occu, che ancestal tock becomes fragmented into ncemiscible ranches, tranches sterile with respect to each other Only onanism in the same branch can mate succesfully 0 that the fragmentation saone-way proces Having happened, ther sno turing back. The same proces operating on ‘much less dre scale than fegmentations ino classes and orders ean ‘imately explain the appearance of species. This picture is stongly supported by the mathematical dicusions of previous chapters, which Showed that changes involving 4 multiplicity of ase pairs can never be {scovered by intemal mutation. Changes even much smaller than those just dacusod cannot are spontaneously Since we ate biological carts, might be expecrd that physical things would exis to serve bog thigs Yer theo thing abou presen dy society is hat ts physical axis appear purpsive ais bila ctv nly weakly 0. Few among us have any real idea of what wear up to, bolegical peking excep 0 sy thar we work aa jb to “ean ving,” ‘oe that we ae “bringing op a fami” or in the case of the young hat we ane rearing finda ob to cama living. rt finda partner torngupa family Frankly speaking now: jt these potstaton oul in principle he give ‘byacow munching na fi. Migratory bids moving withthe seasons often with gat inherent sil and seemingly with consderble knowledge of cetahy, could be atid co daplay @ sperior sense of purpose, which i esha why so many hua ate fiscinated by the pratice of d-watching ‘What i evidently mising from presntaby society is biological knowledge ofthe sme high quality 2» che pbysleal knowledge which at resent guides cue activites, bat which by elf an only be ames. The Inajr reo Believe, why biological knowledge has 0 fara ie impact ‘on sciety i that this 20 proper foundation. The mistaken extrapolation fiom evolition in the small r evolution in the Tange that followed the Darwinian theory of 1859 Ted ocr tc bog which has only grown deeper she piney otJust as our physical knowlege i expreable in mathematical for, 50 ‘nus biological knowledge fics ever to have a eal spat on soc Here TTean only give afew hints of what might he posable. Is aguinst the constraint ofthe population number NV sstainable bythe enviceent hat selection and evolution take place. Humans difer from al ther animals in that N depends to 2 majoe depie on knowledge. That poses by Stone Age humans was suficiene ro malatain tora population exited to have been about 10% Modem knowledge, on the ocher hand, could probably sustain a world population of 10 an immense diference. While the dominant component of novledge this point hasbeen how to gow food under contrlled conditions and how eo manufacture arcles with concomitant acces to large sources of enegy, the pychological attitude of hhumars to themselves is Beginning ro affect “knowlege” and s wo become A pat of our environment. Peycholopcal aries have ll inthe present cenzury to & new and potentially important development in Westem Europe, analy to N taking value appecialy les than che population could have been if ruber ad been pressed to their logit limits. A consequence is thatthe javerle population M eno longer mich lnger thn NY astaton which led ily to the moder concept of a compassionate society If this concept not to be a temporay notion, it i exential that N be prevented from rising sphere nea lite limit. One can say thatthe potential fr butane tw contrat their environments cdetermined hy the extent ra which N iskept bow the logic limit, 1 say. For N appecibly es than the potenti for compasion get, for N approaching NV compassion comes dificu le for N = N20 eoasion a alls posse since N = imple turn ‘othe aw biological conor cht obtain for mest specie, and which have obtainal for humans Uoughont mos oftheir histone ‘The ercamstance tha at the bith of every oping half of ts 80 parent’ gens are dicared creates the pansblity that biologcl knomledae can be atleast as crucial to out environment ip the fire ae physical knowledge as been in the past Ar present and throughout histor, the scan proces happens ese at andor, Bult random dicading be weplaced by contilled discarding and everything would he changed. The read for juveniles 10 be perperully seceiced in order 10 mainain the genetic lnegty of ou species would dappeae. The discarding of genes at random in the eduction of gametes ant continue of eonrie but the choice fe of which pametes frie wo produe ofpring need not heat random, Only fpmeres with fewer than the average number of genetic defect need be fetes that only fring with Feehan the average umber of defects fare born, None would then need to be scrificed. Indeed, by exercising choice over which pametes fete and whieh do no, ll presen defect ould be eliminated from the human species in only a fe goncrations. Hluman abies dh a peal nowadays between chose iva who are hnonly ood at some activity whether physical or mental, and those who tre abnormally bad The effect overa number of generations of removing all, defects woud be to put everone in the abnormally good category and wo do so fr every activi. There would he a complete removal ofthe hither stained misery of those who are born handicapped, he later Being a ects consequence ofthe presen sination in which hd genetic choices aa ily egos choices, with a weeding ou ofthe ba being ee othe ‘uferng f unfortunate individuals ‘Geant thatthe whole genetic complement of the human species i male 0 work in everbody t mote ce les maximum eficiency, what then? ‘Would we mish therester to Become genetically fed, a complex example of living foil? Presumably not. Bat the natual atemative of submitting ‘ules oransom genetic explosion in the next genetic storm invade the arth dos noe appear attractive ether Rather woud our instincts be to hid curves i some way of other from te effcs of serious disease, let alone ffom the fill consequences of a major genetic stoen- ‘The remaining stematie for change i o apie new genes ico our DNA ina controled ‘ea posbity that meer genetic engineering bing into range To ma. ‘sch a pomiblty arouses dstraughe visions of Frankenstein monte. There ‘would cerainly be no shontage of opponents on the respect that nobody fn authority today scems to have much grip on what they are doing, I woud shore this fst. Buco ogc fi were leary demenseable that one could foie anew gene with itl fs and other hat provided immunity sist the common col, or one woe e gd raha i Cancer my possi abe from an inmanity problem, an fnew gene paving immsnity sist cancer were avilable most people Taupe would be ony eo gla to aegure ie The problem les inthe am but in ae present-day lack of knowl, jus sit cd for contri the physic sciences ‘We saw in Chapter 5 thatthe amour of expressed DNA mammals is very likely limited by the pessure of deleterious mutations, bythe factor B29-2. Wit chi pessre emoved in humans, through conta over choices of gametes, the toa of exprewed DNA exuld be incre without pena, therchy opening the read 1 evluonay attainments tha echerise woul be unweachable Such a developrnear would evidenly be aver lon fa Yer to so questing an animal as the human, it simportant to conceive ‘har the rod ro an evermally much superior satus is not inevoebly ‘locked, aie would appear to beso ong me random choices of gamers continue rl the dy(Re pope € ot / on be ny Wot peng possi bt, A, ott Fetter A> Ae setetive fate s = = QUAN