I
n February of2001, Craig Venter, presi-dent ofCelera Genomics, commentingon the near-completion ofthe humangenome project, said that “we are allessentially identical twins.” A newsheadline at the time made a similarpoint:
Are We All One Race? Modern Sci-ence Says So.
In the article that followed,the author quoted geneticist KennethKidd: “Race is not biologically de½nable,we are far too similar.”Venter and Kidd are eminent scien-tists, so these statements must be rea-sonable. Based on an examination ofour
dna
, any two human beings are 99.9percent identical. The genetic differ-ences between different groups of human beings are similarly minute.Still, we only have to look around tosee an astonishing variety ofindividualdifferences in sizes, shapes, and facialfeatures. Equally clear are individual dif-ferences in susceptibility to disease–andin athletic, mathematical, and musicalabilities. Individual differences extend todifferences between group averages.Most ofthese average differences areinconspicuous, but some–such as skincolor–stand out.Why this curious discrepancy betweenthe evidence of
dna
and what we canclearly see? Ifnot
dna
, what are thecauses ofthe differences we perceivebetween individuals and between groupsofhuman beings?
D
na
is a very long molecule, com-posed oftwo strands twisted aroundeach other to produce the famous doublehelix. There are forty-six such
dna
mol-ecules in a human cell, each (along withsome proteins) forming a chromosome.The
dna
in a human chromosome, if stretched out, would be an inch or morein length. How this is compacted into amicroscopic blob some 1/1000 inch longwithout getting hopelessly tangled is anengineering marvel that is still a puzzle.The “business” part ofthe
dna
, thepart that carries genetic information, isthe sequence ofnucleotides, or bases, in
Dædalus Winter 2002
81
James F.Crow
Unequal by nature:a geneticist’s perspectiveon human differences
James F. Crow, a Fellow of the American Acade-my of Arts and Sciences since 1966, is professoremeritus of medical genetics at the University of Wisconsin. Over a career that has spanned morethan ½fty years, he and his collaborators have studied a variety of traits in Drosophila, dissectedthe genetics of
ddt
resistance, measured theeffects of minor mutations on the overall ½tness of populations, described the behavior of mutationsthat do not play the game by Mendel’s rules, stud-ied the effects of nonrandom mating, and consid-ered the question “What good is sex?”
the molecule. There are four ofthese,commonly designated as
A
,
G
,
T
, and
C
.(I could tell you what these letters standfor, but you wouldn’t understand thisessay any better ifI did, so I won’t.)In the double helix, there are fourkinds ofbase pairs:
AT
,
GC
,
TA
, and
CG
.The speci½c pairing rules–
A
with
T
and
G
with
C
–are dictated by the three-dimensional structure ofthe bases.In a chromosome, the base pairs are ina precise sequence, and the orderlyprocess ofcell division assures the repro-duction ofthis sequence with remark-ably few errors. Chromosomes occur inpairs, one member ofeach pair fromeach parent, and the
dna
sites in thetwo corresponding chromosomes matchup. We have twenty-three pairs ofchro-mosomes, or a total offorty-six, as previ-ously mentioned, in each cell. Theseforty-six chromosomes contain aboutsix billion base pairs. Ifwe randomlychoose a pair ofbases from correspon-ding sites in two persons, 99.9 percent of the time they will be the same. This per-centage depends only slightly onwhether the two people are from thesame or from different continents, fromthe same or from different populationgroups.In order to make sense ofhow the
dna
ofhuman beings can be so similar,despite all the important visible andphysiological differences among individ-uals and groups, it is helpful to recountour evolutionary history.All mammals, including ourselves, aredescended from an ancestral species thatlived about one hundred million yearsago. In our mammalian ancestry an aver-age base has changed, say from an
A
to a
T
, at the almost unbelievably slow rate of about one change per billion years. Thismeans that only a small fraction ofthebases, one hundred million divided byone billion, or 1/10, have changed duringthat time. As a result, we share roughly90 percent ofour
dna
with mice, dogs,cattle, and elephants.Coming closer to home, the
dna
of human beings and chimpanzees is 98 to99 percent identical. The differencesbetween us that we (and presumably thechimps) regard as signi½cant depend ononly 1 or 2 percent ofour
dna
.Much ofhuman
dna
is very similar toeven more remote ancestors: reptiles, in-vertebrates, and even plants. All livingthings share many functions (e.g., respi-ration) going back to a very distant past.Most ofour
dna
determines that we arehuman, rather than determining how weare different from any other person. So itis not so surprising that the
dna
ofanytwo human beings is 99.9 percent identi-cal.What produces variability betweenindividual organisms–and makes possi-ble evolutionary change–is errors in the
dna
copying process. Sometimes,because ofthis, one base is changed toanother–it mutates. Among the six bil-lion base pairs each ofus inherits fromour parents, a substantial number–ahundred or more–are new mutations.How can we reconcile this large num-ber with the extremely slow rate ofevo-lutionary change? The explanation isthat only a tiny fraction ofmutationspersist over time. Some mutations sur-vive as a matter ofeither luck or–ifthemutation confers a biological advan-tage–natural selection. Even ifadvanta-geous, an individual mutation has littlechance ofsurviving a long evolutionarytrip. The slow rate ofevolutionarychange explains why we mammals are sosimilar in our
dna
.Molecular studies of
dna
have beenextremely fruitful in working out theevolutionary history oflife. Much of what we know about human ancestrycomes from
dna
studies, supplemented82
Dædalus Winter 2002 James F.Crowoninequality
by a rather spotty fossil record. The
dna
evidence strongly supports the idea thatthe human species originated in Africa,and that European and Asiatic popula-tions–indeed, all non-Africans–aredescended from a small number of migrants from Africa. The strongest evi-dence for this is that Africans are morevariable in their
dna
than are other pop-ulations.Analysis of
dna
allows us to measurewith some precision the genetic distancebetween different populations ofhumanbeings. By this criterion, Caucasians andAsians are relatively similar, whereasAsians and Africans are somewhat moredifferent. The differences between thegroups are small–but they are real.
dna
analysis has provided excitingnew answers to old questions. But its½ndings can also be misleading. Take thecase ofmen and women and sex chro-mosomes. Females have two
X
chromo-somes, while males have an
X
and a
Y
.The
Y
chromosome makes up perhaps 1percent ofthe
dna
. But there is very lit-tle correspondence between the
Y
andthe other chromosomes, including the
X
.In other words, the
dna
ofa humanmale differs as much from that ofafemale as either does from a chimpanzeeofthe same sex. What does this mean?Simply that
dna
analysis, which hasgiven us a revolutionary new under-standing ofgenetics and evolution,doesn’t give sensible answers to somecontemporary questions that society isinterested in.
M
ost ofthe differences that we noticeare caused by a very tiny fraction ofour
dna
. Given six billion base pairs percell, a tiny fraction–1/1000 ofsix billionbase-pairs–is still six
million
differentbase pairs per cell. So there is plenty of room for genetic differences among us.Although we differ from each other in avery tiny proportion ofour
dna
, we dif-fer by a large number of
dna
bases.Some noteworthy evolutionarychanges in human beings have occurredrelatively rapidly, despite the slow over-all rate ofchange at the
dna
level. Thedifference between the skin color of Africans and Europeans probablyevolved in less than ½fty thousand years,an adaptation to differences in climate.Still more rapid were changes in genesthat confer resistance to malaria inAfrica and Mediterranean regions; itonly took between four and eight thou-sand years for the new genes to evolve.What genetic analysis reveals is thatsome ofthe genetic changes that seem sosigni½cant to us depended on a very tinyfraction ofour
dna
.But, as I said, this tiny fraction is still avery large number ofbases. No twohuman beings are alike in the traits theypossess. Some are tall, others are short;some are stocky, others thin; some aregifted musically, others tone deaf; someare athletic, others awkward; some areoutgoing, others introverted; some areintelligent, others stupid; some canwrite great poetry or music, most can-not. And so on.To understand our differences, weneed to consider not just
dna
, but itscellular products as well. This area of study is new, but it is progressing rapid-ly. The emphasis is changing from
dna
sequences to genes. A gene is a stretch of
dna
, usually several thousand base pairslong. The function ofmost genes is toproduce proteins. The genome sequenc-ing project has revealed that we humanshave thirty to forty thousand genes. Butsince a gene often produces more thanone kind ofprotein, sometimes produc-ing different kinds for different bodyparts, the number ofkinds ofprotein ismore like one hundred thousand.We share a number ofgenes with
Dædalus Winter 2002
83
Unequalby nature
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