275:R1455-R1460, 1998.

; Am J Physiol Regul Integr Comp Physiol

Loyal Britton
Lauren Gerard Koch, Todd A. Meredith, Teigen D. Fraker, Patricia J. Metting and Steven
Heritability of treadmill running endurance in rats
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Heri tabi l i ty of treadmi l l runni ng endurance i n rats
LAUREN GERARD KOCH, TODD A. MEREDI TH, TEI GEN D. FRAKER,
PATRI CI A J. METTI NG, AND STEVEN LOYAL BRI TTON
Department of Physiology and Molecular Medicine, Medical College of Ohio,
Toledo, Ohio 436145804
Koch, Lauren Gerard, Todd A. Meredith, Teigen D.
Fraker, Patricia J . Metting, and Steven Loyal Britton.
Heri tabi l i ty of treadmi l l runni ng endurance i n rats. Am. J .
Physiol. 275 (Regulatory I ntegrative Comp. Physiol. 44):
R1455R1460, 1998.Treadmi l l runni ng was eval uated as a
phenotype for sel ecti ve breedi ng for hi gh- and l ow-endurance
performance from a starti ng popul ati on of 18 mal e and 24
femal e outbred Sprague-Dawl ey rats. Each rat was exerci sed
to exhausti on once per day for 5 consecuti ve days. The
treadmi l l was set at a constant 15 sl ope, and the i ni ti al
vel oci ty of 10 m/mi n was i ncreased by 1 m/mi n every 2 mi n.
The total di stance run on the si ngl e best day out of the ve
tri al s was taken as the measure of endurance performance.
The ori gi nal popul ati on (mal es and femal es combi ned, n
42) ran on average for 396 m. The two l owest-performi ng
pai rs and two hi ghest-performi ng pai rs were sel ecti vel y bred
through three successi ve generati ons. After three generati ons
of sel ecti on, performance of the offspri ng from the hi gh
sel ected l i ne averaged 659 36 m (n 20), whereas
l ow-performance offspri ng (n 13) averaged 388 28 m. The
narrow-sense heri tabi l i ty, cal cul ated as the regressi on of
i ndi vi dual offspri ng performance on mi dparental val ue for
each fami l y, was 0.39 across the three generati ons. Thi s
i mpl i es that 39% of the vari ati on i n runni ng endurance
performance between the l ow and hi gh sel ected l i nes was
determi ned by heri tabl e factors.
geneti c model s; exerci se; i nbred strai ns; pol ygeni c trai t;
aerobi c capaci ty
AN AEROBI C ENDURANCE exerci se test i s often used to
assess cardi ovascul ar tness and to esti mate the mag-
ni tude of the cardi ovascul ar reserve capaci ty (7, 9, 11).
Aerobi c capaci ty of an organi sm i s l i kel y pol ygeni c i n
ori gi n and i s subsequentl y i nuenced to varyi ng de-
grees by envi ronmental factors. Trai ts such as endur-
ance are often referred to as mul ti factori al to empha-
si ze thei r deter mi nati on by mul ti pl e geneti c and
envi ronmental factors.
Si mpl e addi ti ve model s of heredi ty pl us envi ronment
have been uti l i zed to esti mate the geneti c contri buti on
to the vari ance i n endurance performance i n monozy-
goti c and di zygoti c twi ns. Al though the assumpti ons of
twi n studi es are often not compl etel y ful l l ed or veri -
abl e (10), Kl i ssouras (14) esti mated that the vari abi l i ty
i n maxi mal aerobi c power, as measured by treadmi l l
runni ng to exhausti on, i s 93.4%geneti cal l y determi ned
i n uncondi ti oned humans. I f i ndeed there i s a l arge
geneti c component to a phenotype as fundamental to
heal th and survi val as endurance performance, the
i denti cati on of the geneti c substrate that di ctates the
di fference between l ow- and hi gh-endurance perfor-
mance woul d be of major i mportance.
A starti ng poi nt for i denti cati on of genes that
di ctate the di fferences i n the phenotypi c expressi on of
trai ts of pol ygeni c ori gi n i s to create strai ns that
di verge to the extremes of the trai t of i nterest by
sel ecti ve breedi ng (18). Sel ecti ve breedi ng for a gi ven
phenotypi c trai t i s most effecti vel y achi eved i f 1) a
quanti tati ve, conveni ent, and repeatabl e measure of
the trai t can be devi sed and 2) the measure of the trai t
i s markedl y vari ant i n an outbred popul ati on.
The purpose of thi s study was to eval uate the sui tabi l -
i ty of usi ng treadmi l l runni ng i n rats as a phenotype for
sel ecti ve breedi ng for l ow and hi gh aerobi c endurance
performance. Our resul ts demonstrate that treadmi l l
endurance runni ng i n rats has characteri sti cs favor-
abl e for sel ecti ve breedi ng for thi s trai t. Under the
condi ti ons of hi gh i ntensi ty of sel ecti on, i n a rel ati vel y
smal l popul ati on, the narrow-sense heri tabi l i ty (h
2
)
was 0.39 over the rst three generati ons. Devel opment
of these types of model s wi l l provi de a cri ti cal substrate
for eval uati ng the functi onal genomi cs of compl ex
trai ts.
METHODS
Animals. The starti ng popul ati on was 24 mal e and 24
femal e outbred Sprague-Dawl ey rats (Harl an Sprague Daw-
l ey, I ndi anapol i s, I N). Each rat was of di fferent parentage so
that endurance performance was not compared between
brothers and si sters, whi ch woul d tend to narrow the geneti c
vari ance. The rats were 10 wk ol d on arri val at our i nsti tuti on
and were housed for 1 wk to al l ow for stabi l i zati on from any
stress accrued duri ng shi ppi ng. Each rat was provi ded food
and water ad l i bi tum and was pl aced on a 12:12-h l i ght-dark
cycl e wi th the l i ght cycl e occurri ng duri ng dayti me.
Experimental protocol. The i ni ti ati on to the treadmi l l was
performed Monday through Fri day for 1 wk, and endurance
testi ng was performed Monday through Fri day on the subse-
quent week. The rst week consi sted of i ntroduci ng each rat
to the treadmi l l (model Exer-4; Col umbus I nstruments, Co-
l umbus, OH) for gradual l y i ncreasi ng durati ons each day. The
goal was to i denti fy those rats that were trai nabl e to the
extent of bei ng abl e to run for 5 mi n at a vel oci ty of 10 m/mi n
on a sl ope of 15. The abi l i ty to achi eve thi s mi ni mal l evel of
runni ng abi l i ty at l east one ti me consti tuted the threshol d
performance necessary to be i ncl uded i n the group that woul d
be eval uated for endurance the fol l owi ng week. Thi s amount
of exposure to treadmi l l runni ng i s bel ow that requi red to
produce a measurabl e change i n aerobi c capaci ty (1, 4). Al l
rats not achi evi ng thi s mi ni mal runni ng abi l i ty were ex-
cl uded from further consi derati on.
The rst 2 days of i ntroducti on to treadmi l l runni ng
consi sted of si mpl y pl aci ng the rat on the bel t that was
movi ng at a vel oci ty of 5 meters/mi n (15 sl ope) and pi cki ng
the rat up and movi ng i t forward i f i t started to sl i de off the
The costs of publ i cati on of thi s arti cl e were defrayed i n part by the
payment of page charges. The arti cl e must therefore be hereby
marked advertisement i n accordance wi th 18 U.S.C. Secti on 1734
sol el y to i ndi cate thi s fact.
0363-6119/98 $5.00 Copyri ght

1998 the Ameri can Physi ol ogi cal Soci ety R1455

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back of the bel t; that i s, the rats were not al l owed to sl i de onto
the 15 15 cm el ectri c shock gri d l ocated at the back of the
treadmi l l . Duri ng i ntroducti on days 35, the bel t speed was
i ncreased to 10 m/mi n and fai l ure to run caused the rats to
sl i de off of the movi ng bel t and onto the shock gri d that
del i vered 1.2 mA of current at 3 Hz. The rats were l eft on the
gri d for 1.5 s and then moved forward onto the movi ng bel t.
Thi s process was repeated unti l the rats l earned to run to
avoi d the mi l d shock.
Rats achi evi ng the threshol d performance duri ng week 1
were eval uated for maxi mal endurance runni ng for 5 consecu-
ti ve days duri ng week 2. Each dai l y endurance tri al was
performed at a constant sl ope of 15, wi th the starti ng
vel oci ty at 10 m/mi n; runni ng performance was eval uated at
about the same ti me each day (between noon and 2 PM). The
vel oci ty was i ncreased by 1 m/mi n every 2 mi n, and each rat
was run unti l exhausti on. Exhausti on was operati onal l y
dened as the thi rd ti me the rat was wi l l i ng to sl i de onto the
shock gri d and sustai n 2 s of shock rather than run. At the
moment of exhausti on the current to the gri d was stopped
and the rat was removed from the treadmi l l .
For each of the ve tri al s, the total di stance run (m) was
used as the esti mate of endurance performance. The si ngl e
best dai l y run of ve tri al s for each rat was consi dered the
tri al most cl osel y associ ated wi th the heri tabl e component of
runni ng endurance performance. Al l esti mates of perfor-
mance descri bed i n thi s study are based on thi s si ngl e best
day of performance from each rat.
Selective breeding. By the si ngl e best day performance
cri teri on, the two l owest- and two hi ghest-performi ng rats of
each gender were sel ected and pai red for mati ng at each
generati on. The offspri ng (2 l i tters from the hi gh-perfor-
mance parents and 2 l i tters from the l ow-performance par-
ents) were weaned at 30 days after bi rth. At 11 wk of age the
offspri ng were i ntroduced to the treadmi l l and subsequentl y
tested for endurance as descri bed above for the ori gi nal
popul ati on of rats.
The heri tabi l i ty of endurance performance was esti mated
i n the narrow sense (h
2
) and was cal cul ated as the regressi on
of i ndi vi dual offspri ng performance on mi dparent perfor-
mance per fami l y. The val ue for mi dparent performance was
cal cul ated as the mean performance of the femal e and mal e
parents of each fami l y (8). I f h
2
1, then the trai t was on
average i nheri ted wi th compl ete del i ty, whereas an h
2
0
demonstrates no heri tabl e si mi l ari ty between parents and
offspri ng.
Data are reported as mean val ues SE. Si gni cance of
di fferences was eval uated wi th Students t-test for compari -
son between gender and between sel ected l i nes. Dunnetts
test was used for mul ti pl e compari sons to the ori gi nal popul a-
ti on wi thi n each sel ected l i ne (19), and di fferences were
consi der ed si gni cant i f the computed pr obabi l i ty (P)
was 0.05.
RESULTS
Performance of original population. Al l 24 of the
femal es from the ori gi nal popul ati on were abl e to
sati sfy the mi ni mal runni ng performance to be i n-
cl uded i n the group that went on for endurance testi ng.
The femal es ran for an average durati on of 27.2 mi n,
whi ch equated to an average di stance of 445 18 m on
thei r best day of performance (range 346695 m).
Ei ghteen of the twenty-four mal es were abl e to meet
the mi ni mum cri teri a for eval uati on i n the endurance
test. The mal es ran for an average durati on run of
21.8 1 mi n and an average di stance of 331 21 m on
thei r best day of performance (range 149544 m).
The femal e rats i n the ori gi nal popul ati on wei ghed l ess
(205 1 vs. 302 3 g) and ran both si gni cantl y l onger
(5.4 min) and further (114 m) than the males (Table 1).
Fi gure 1A shows the dai l y performances for each of
the femal es i n the ori gi nal popul ati on. The ve dai l y
runs are presented from the worst day of performance
(day5) to the best day of performance (day1); these 120
runs i n 24 femal e rats were found not to be di fferent
from a normal di stri buti on as assessed by the Kol -
mogorov-Smi rnov test (Li l l i efors P val ue 0.0159)
(19). I n general , for thi s group and al l others, the
rel ati ve ranki ng order of performance for a gi ven rat
was consi stent. That i s, superi or performers retai ned
thei r superi or rank and i nferi or performers retai ned
thei r i nferi or rank wi th each eval uati on. Fi gure 1B
shows the dai l y runs for the mal e rats ranked from the
worst (day 5) to best (day 1) day of performance; these
Tabl e 1. Summarydata of endurancerunning
performancein original population and generation 1
Number
of Rats
Body Wei ght,
g
Durati on
of Run,
mi n
Di stance Run,
m
Ori gi nal popul ati on
Al l rats 42 N/A 24.90.7 39616
Femal es 24 2051* 27.20.8* 44518*
Mal es 18 3023 21.81.0 33121
Generation 1l ow
Al l rats 27 N/A 26.91.0 44924
Femal es 16 2004* 29.41.3* 50230*
Mal es 11 3047 23.81.4 37231
Generation 1hi gh
Al l rats 25 N/A 31.01.5 58135
Femal es 14 2183* 34.81.8* 64351*
Mal es 11 3415 29.31.8 50242
Val ues are means SE. N/A, not appl i cabl e. *Femal es si gni -
cantl y di fferent from mal es (P0.05). Si gni cantl y di fferent from
ori gi nal popul ati on (P0.05).
Tabl e 2. Summarydata of endurancerunning
performancein generations 2and 3
Number
of Rats
Body Wei ght,
g
Durati on of Run,
mi n
Di stance Run,
m
Generation 2l ow
Al l rats 25 N/A 26.10.9 42321
Femal es 9 18510* 28.81.3* 48532*
Mal es 16 3086 24.51.1 38823
Generation 2hi gh
Al l rats 31 N/A 34.11.0 62125
Femal es 16 2012* 34.61.6 63841
Mal es 15 3033 33.51.2 60430
Generation 3l ow
Al l rats 13 N/A 24.51.3 38828
Femal es 8 1974* 24.12.0 38041
Mal es 5 3079 25.21.5 40133
Generation 3hi gh
Al l rats 20 N/A 35.41.3 65836
Femal es 10 21610* 38.91.4* 75340*
Mal es 10 31610 31.91.7 56443
Val ues are means SE. *Femal es si gni cantl y di fferent from
mal es (P0.05). Si gni cantl y di fferent from ori gi nal popul ati on
(P0.05) (see Tabl e 1).
R1456 SELECTI VE BREEDI NG FOR ENDURANCE PERFORMANCE

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90 runs i n 18 mal e rats were found not to be di fferent
from a normal di stri buti on (Li l l i efors P val ue 0.0275).
Fi gure 2 shows a ranki ng of the best performance by
each rat (mal es and femal es combi ned) from the hi gh-
est to l owest di stance run for the ori gi nal popul ati on
and the rst generati on of sel ecti on. The ori gi nal
popul ati on contai ned 42 rats that ran for an average of
396 16 m wi th a range from 695 to 149 m. The
average di stance run by the 27 l ow-performance off-
spri ng was 449 24 m (range 186721 m), whi ch
was not si gni cantl y di fferent (P 0.131) from the
performance of the ori gi nal popul ati on. The average
di stance run by the 25 hi gh-performance offspri ng was
581 35 m, wi th a range from 271 to 1,095 m, whi ch
was si gni cantl y greater than the ori gi nal popul ati on
(P 0.0001) and represents an average i mprovement
of 185 m. Onl y 3 of the 25 hi gh-performance offspri ng
achi eved runni ng di stances that were l ess than the
average of the original population. On average, offspring
from the low-performance parents were not different from
the original population, whereas the high-performance
offspring were signicantly greater by 46.7%.
Responsetoselection. Fi gure 3 shows the response to
sel ecti on at each of the three generati ons. I n generation
1 there was a nonsi gni cant i ncrease i n the perfor-
mance of the l ow-sel ected l i ne and a l arge i ncrease i n
the hi gh-sel ected l i ne. Presumabl y, thi s i mprovement
i n both l i nes over the ori gi nal popul ati on represents an
envi ronmental response (the ori gi nal popul ati on was
born and rai sed for the rst 10 wk i n the col oni es of
Harl an Sprague Dawl ey). Despi te thi s apparent envi -
ronmental i nuence, the l i nes di verged si gni cantl y by
29%i n the rst generati on (132 m di fference). Response
to sel ecti on conti nued i n generations 2 and 3 (Tabl e 2).
By generation 3, the l i nes were separated i n perfor-
mance by 70%or di fferent by 271 m of di stance run.
Heritability of running endurance. Fi gure 4 shows
the regressi on of the runni ng performance for the
i ndi vi dual offspri ng for each fami l y on the mean perfor-
mance of the parents from whi ch those offspri ng were
deri ved. Runni ng performances for 12 parental pai rs
(mi dparent val ues) and thei r offspri ng are represented
(i .e., 2 l i tters each for both hi gh- and l ow-sel ected l i nes
across 3 generati ons). I n general , the runni ng perfor-
mance of the parents was a si gni cant predi ctor of the
performance of the offspri ng. Approxi matel y 32%of the
vari ance (r 0.57) i n performance i n the parents was
associ ated posi ti vel y wi th the vari ance i n the perfor-
Fi g. 1. Each thi n sol i d l i ne connects
ve dai l y runni ng performances ranked
from l owest (day 5) to hi ghest (day 1)
di stance run for each femal e (A) and
mal e (B) rat of the ori gi nal popul ati on.
Thi ck l i ne shows ranked average val ue
wi thi n each group. I n general , rats
retai ned thei r rel ati ve ranki ng on each
tri al . Rats sel ected as breeders for the
start of the l ow and hi gh l i nes are
encl osed by rectangl es.
R1457 SELECTI VE BREEDI NG FOR ENDURANCE PERFORMANCE

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mance of the offspri ng. The regressi on of offspri ng
performance on mi dparental performance, whi ch i s an
esti mate of narrow-sense heri tabi l i ty, was 0.39.
DISCUSSION
Thi s study demonstrates that a phenotype rel ated to
aerobi c endurance performance has characteri sti cs that
are sui tabl e for sel ecti ve breedi ng of thi s trai t. Theoreti -
cal l y, arti ci al sel ecti on can al ter the mean val ue of
essenti al l y any compl ex quanti tati ve trai t i n both
di recti ons i f the starti ng popul ati on i s geneti cal l y heter-
ogeneous (11). We used the fol l owi ng general cri teri a to
gui de the devel opment of a sui tabl e test of endurance
performance: 1) si mpl e to perform, 2) objecti vel y i nter-
pretabl e, 3) gradabl e on a conti nuous numeri cal scal e,
4) demonstrati ng a wi de range i n magni tude between
the l ow and hi gh val ues of the phenotype, 5) normal l y
di stri buted, and 6) requi ri ng rel ati vel y i nexpensi ve
equi pment. Because endurance performance i s a hi ghl y
compl ex trai t, i t seemed parti cul arl y i mportant to
choose a si mpl e yet suffi ci ent test of thi s trai t so that
i nvesti gator-i nduced envi ronmental factors are mi ni -
mi zed.
Several human twi n studi es suggest that endurance
capaci ty has substanti al heri tabi l i ty. Kl i ssouras (14)
esti mated the proporti onal contri buti on of heredi ty to
the i nteri ndi vi dual vari ance i n performi ng an endur-
ance run to exhausti on i n pai rs of monozygoti c and
di zygoti c twi ns; subjects were eval uated at rel ati vel y
young ages (713 yr) because i t strengthened the
assumpti on of a shared envi ronment for both types of
twi ns. He esti mated that the vari abi l i ty i n maxi mal
aer obi c power i s 93.4% geneti cal l y deter mi ned.
Bouchard et al . (2) esti mated that a geneti c component
accounts for 70% of endurance performance i n young
adul ts when measured as the total work performed
duri ng a 90-mi n maxi mal ergocycl e test. Other i nvesti -
gators, however, found onl y mi ni mal (5) or no i nheri t-
abl e components rel ated to measures of maxi mal aero-
bi c performance (12). Al though monozygoti c twi ns are
geneti cal l y i denti cal and phenotypi c vari ance between
twi ns must be of envi ronmental ori gi n, twi n studi es
shoul d not be vi ewed as deni ti ve. A ndi ng of no
si gni cant geneti c component coul d si mpl y resul t from
a l arge vari abi l i ty i n the experi mental measure of the
phenotype of i nterest, especi al l y for a compl ex measure
such as maxi mal oxygen consumpti on (17). On the
other hand, the effect of correl ated envi ronments woul d
tend to i nate the apparent geneti c contri buti on. For
exampl e, monozygoti c twi ns may be treated more si mi -
l arl y by peopl e than di zygoti c twi ns because of thei r
si mi l ar appearance.
Fi g. 2. Di stance run on the best day of performance for each rat for 1)
ori gi nal popul ati on (n 24), 2) hi gh-performance generation 1
offspri ng (n25), and 3) l ow-performance generation1offspri ng (n
27). There was no si gni cant di fference between the di stance run for
the ori gi nal popul ati on and the l ow-performance offspri ng. The
hi gh-performance offspri ng ran si gni cantl y further than the other
two groups. Onl y 3 of the 25 hi gh-performance offspri ng had runni ng
di stances that were l ess than the average of the ori gi nal popul ati on.
Femal es are represented by open symbol s and mal es are represented
by cl osed symbol s.
Fi g. 3. Response to sel ecti on for endurance performance. At each
generati on there was a si gni cant di vergence between the l ow- and
hi gh-sel ected l i nes. By generation 3the l i nes were separated by 70%.
R1458 SELECTI VE BREEDI NG FOR ENDURANCE PERFORMANCE

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From our experi ence wi th treadmi l l runni ng i n rats,
we predi cted that the sel ecti on process woul d more
readi l y produce di vergence of hi gh-performance rats
rel ati ve to the l ow-performance rats. Thi s tenet i s
based on two i deas. 1) The envi ronment can have an
i nni te negati ve i nuence on performance (i .e., take
the di stance run to zero). Factors such as subtl e
di fferences i n housi ng or dai l y handl i ng coul d cause a
geneti cal l y superi or rat to perform bel ow i ts normal
l evel on a gi ven day. 2) The envi ronment can have onl y
a ni te posi ti ve i nuence on endurance performance.
These consi derati ons al so convi nced us to use the si ngl e
best performance of the ve tri al s as bei ng most
exempl ary of the endurance capaci ty associ ated wi th a
geneti c ori gi n. I n short, a negati ve envi ronment coul d
easi l y degrade a geneti cal l y t rat i nto a poor per-
former, but we deemed i t unl i kel y that a posi ti ve
envi r onment coul d tr ansfor m a geneti cal l y bel ow-
normal performer i nto a top performi ng rat that woul d
be sel ected for breedi ng.
We al so consi dered whether the age of the rat at the
ti me of testi ng coul d i nuence i ts performance. At 3 mo
of age the separati on i n performance between the four
l ow-performance and the four hi gh-performance breed-
ers from the ori gi nal popul ati on was 215%. At 6 mo of
age, these same rats were retested and the di vi de i n
thei r performance was 169%. Thus the di vergence i n
performance for i ndi vi dual rats appears to be carri ed
across a l onger durati on.
The absence of si gni cant di vergence for the off-
spri ng from the sel ected l ow-performance parents from
the ori gi nal popul ati on coul d ori gi nate from at l east
two sources of error. Fi rst, as descri bed above, we thi nk
the accuracy of sel ecti on for l ow-performance rats i s
substanti al l y l ess than for hi gh-performance rats. I n-
deed, one or more of the l ow-performance parents may
not have been as geneti cal l y l ow as our test esti mated
because of unknown envi ronmental factors that compro-
mi sed the runni ng performance. Thi s probl em i s of
course more cri ti cal i f i t occurs i n smal l popul ati ons and
was perhaps ampl i ed i n the l ow-sel ected popul ati on
because both l i tters had the same mal e parent; one of
the l ow-sel ected mal es di d not mate successful l y. Sec-
ond, subtl e di fferences i n housi ng condi ti ons may have
i nuenced the average performance for the ori gi nal
popul ati on versus the l ow and hi gh offspri ng. The
ori gi nal popul ati on was born and housed for the rst 10
wk at the Har l an Spr ague Dawl ey Labor ator i es,
whereas the l ow and hi gh offspri ng were born and
rai sed i n the Ani mal Research Faci l i ty at the Medi cal
Col l ege of Ohi o i n Tol edo. The contri buti on from these
two potenti al sources of error are unknown, but the
wi de di vergence i n performance between the offspri ng
of the l ow- versus hi gh-sel ected l i nes across three
generati ons neverthel ess demonstrates a substanti al
heri tabl e component to endurance runni ng.
Studi es i n other ani mal speci es al so demonstrate
that endurance performance has a heri tabl e component
that i s measurabl e. Garl and and hi s col l eagues (3)
found an h
2
of 0.17 for endurance swi mmi ng perfor-
mance i n mi ce and reported an h
2
of 0.70 for treadmi l l
endurance runni ng i n garter snakes (6). Stri ct compari -
sons of heri tabi l i ty between studi es are of l i mi ted val ue
because si ngl e-generati on heri tabi l i ty i s i nuenced by
nonstandardi zed factors that i ncl ude 1) the magni tude
of the breedi ng val ue and 2) the i ntensi ty of sel ecti on
(16).
An ul ti mate goal i s to devel op and uti l i ze sel ecti vel y
bred strai ns to i denti fy the geneti c substrate that
di ctates the di fference between l ow-endurance perfor-
mance and hi gh-endurance performance. One vi ew
supports the hypothesi s that endurance performance i s
determi ned l argel y by two factors: 1) the rate at whi ch
oxygen and nutri ent substrates can be uti l i zed to
produce energy i n the form of ATP and 2) the effi ci ency
wi th whi ch thi s energy i s transferred i nto work (7, 15).
Oxygen uti l i zati on i s governed by the cardi ac output
and the abi l i ty of peri pheral ti ssues to extract oxygen.
Effi ci ency i s the rati o of work performed to total energy
expended and i s determi ned by the compl ex i nteracti on
of al l factors that transl ate energy i nto movement, such
as skel etal mechani cs, neuromuscul ar coordi nati on,
and heat di ssi pati on. Gi ven the compl exi ty of endur-
ance performance, i t i s i mpossi bl e to predi ct the exact
nature of the vari ous i ndi vi dual trai ts that wi l l be
produced by arti ci al sel ecti on. Neverthel ess, i t seems
reasonabl e to predi ct that major geneti cal l y medi ated
Fi g. 4. Endurance performance of i ndi vi dual offspri ng regressed on
parental performance for each of the 12 fami l i es (2 l i nes, 2 mated
pai rs across 3 generati ons). Mi dparent val ues are the parental
average for each fami l y. Approxi matel y 32%of the vari ati on (r 0.57)
i n the mi dparental val ues was associ ated posi ti vel y wi th vari ati on i n
the val ues of the offspri ng. Narrow-sense heri tabi l i ty, esti mated from
the regressi on of offspri ng val ues on mi dparent val ues, was 0.39.
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di fferences i n the abi l i ty of the heart to create a cardi ac
output wi l l be at l east one of the factors sel ected for.
Joyner (13) has devel oped a more expl i ci t model of
endurance runni ng performance that i n i ts si mpl est
form i s the product of three physi ol ogi cal factors: 1) the
maxi mal rate at whi ch oxygen and nutri ent substrates
can be uti l i zed (V

O
2max
) to produce energy i n the form
of ATP, 2) the percent of V

O
2max
at the threshol d
for l actate rel ease, and 3) the effi ci ency of runni ng.
Each of these i ntermedi ates i s pol ygeni c i n ori gi n and
hi ghl y compl ex i n physi ol ogi cal expressi on. We hypoth-
esi ze that al l el i c di ffer ences di ctati ng cumul ati ve
changes i n each of these three i ntermedi ate phenotypes
wi l l l argel y account for the magni tude of the di fference
i n performance between sel ected l i nes for l ow- and
hi gh-endurance performance.
I n summary, these resul ts demonstrate that tread-
mi l l runni ng endurance i s a trai t wi th a substanti al
heri tabl e component. Based on a smal l outbred popul a-
ti on of Sprague-Dawl ey rats, the treadmi l l runni ng test
we devi sed to assess endurance performance was nor-
mal l y di stri buted and demonstrated a wi de range
between l ow and hi gh val ues for whi ch to sel ect for
endurance performance. Sel ecti on was based on the one
best day of performance, whi ch seemed most appropri -
ate because acute envi ronmental factors can easi l y
i nuence performance on any si ngl e day. The parents
sel ected from thi s ori gi nal popul ati on based on ei ther
l ow-endurance performance or hi gh-endurance perfor-
mance produced offspri ng that were di vergent i n perfor-
mance over three generati ons. Wi th appropri ate di ver-
gent strai ns as a starti ng poi nt, one wi l l ul ti matel y
be abl e to i denti fy genes that are causati ve of the
di fference between l ow- and hi gh-endurance perfor-
mance.
Address for repri nt requests: S. L. Bri tton, Physi ol ogy and Mol ecu-
l ar Medi ci ne, Medi cal Col l ege of Ohi o, 3035 Arl i ngton Ave., Tol edo,
OH 436145804.
Recei ved 12 January 1998; accepted i n nal form 17 Jul y 1998.
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