Association between hybrid status and reproductive success of captive male and female rhesus macaques (Macaca mulatta) at the California National Primate Research Center (CNPRC).код для вставкиСкачать
American Journal of Primatology 73:671–678 (2011) RESEARCH ARTICLE Association Between Hybrid Status and Reproductive Success of Captive Male and Female Rhesus Macaques (Macaca mulatta) at the California National Primate Research Center (CNPRC) SREE KANTHASWAMY1,2, PARRY M.R. CLARKE1, ALEXANDER KOU2, VENKAT MALLADI3, JESSICA SATKOSKI TRASK1, AND DAVID GLENN SMITH1,2 1 Department of Anthropology, California National Primate Research Center, University of California-Davis, Davis, California 2 California National Primate Research Center, University of California-Davis, Davis, California 3 Center for Biomolecular Science and Engineering, School of Engineering, University of California-Santa Cruz (UCSC), Santa Cruz, California The California National Primate Research Center (CNPRC) houses more than 1,000 rhesus macaques (Macaca mulatta) of mixed Chinese–Indian ancestry. Most of these animals are kept in outdoor field cages, the colony’s long term breeding resource. Since 2001, hybrids comprised between 4 and 49% of the field cage populations, but in most cases have represented a maximum of 10% of those populations. The increasing prevalence of hybrids is partly due to management efforts to distribute genetic diversity effectively and minimize genetic subdivisions. However, other factors may also contribute to the spread of hybrids within the colony, most notably variance in socio-sexual behaviors and physical attributes. It is known that hybrids of some species exhibit heterosis, such as early maturation, that can enhance reproductive success, and anecdotal observations of mixed groups of hybrid, Indian and Chinese animals at the CNPRC suggest that hybrids are more sexually active. To determine whether hybrids experienced a reproductive advantage, a study was conducted using birth records of 5,611 offspring born in the CNPRC colony between 2003 and 2009. We found that while the degree of Chinese ancestry (DCA) appeared to influence the maturational schedule of both males and females (maturation was inversely related to proportion of Chinese ancestry), DCA had no independent effect on either male or female RS or rank. Therefore, we have found no evidence that a hybrid phenotype confers an absolute reproductive advantage in our colony. Am. J. Primatol. 73:671–678, 2011. r 2011 Wiley-Liss, Inc. Key words: hybridity; hierarchical rank; reproductive success; captive colony management INTRODUCTION The ability to identify associations between alleles and disease phenotypes can be diminished in inbred or highly genetically homogeneous animals because reduced genetic variation among research subjects reduces the probability that rare causal alleles will be present in the population. On the other hand, the use of animals from different geographic origins and/or their hybrids with very high genetic variation can confound interpretations of phenotypic differences of complex additive traits and disease because it inflates the phenotypic variance of traits with high heritability. Such variation requires the use of a greater number of research subjects to detect biologically meaningful differences between experimental and control groups. Therefore, a balance must be struck between meeting the research community’s need for genetically heterogeneous stocks and a simple and less variable model system. An advantage of using hybrid animals in biomedical research is that hybrids with disease r 2011 Wiley-Liss, Inc. phenotypes whose frequency differs between the two parental populations have an increased probability of inheriting alleles linked to genes conferring susceptibility inherited from the parental population with higher susceptibility. This is the underlying principle of admixture mapping [Reich & Patterson, 2005], which is useful for mapping disease-causing genetic variants that vary in frequency between Indian and Chinese rhesus macaques. The genomic location of Contract grant sponsor: California National Primate Research Center (CNPRC); Contract grant numbers: RR000169-48; RR018144-07; Contract grant sponsor: NIH; Contract grant numbers: RR005090; RR025871. Correspondence to: Sree Kanthaswamy, Department of Anthropology, California National Primate Research Center, University of California-Davis, Davis, CA 95616. E-mail: firstname.lastname@example.org Received 15 November 2010; revised 23 February 2011; revision accepted 25 February 2011 DOI 10.1002/ajp.20948 Published online 23 March 2011 in Wiley Online Library (wileyonlinelibrary.com). 672 / Kanthaswamy et al. susceptibility genes with a higher frequency in Chinese than in Indian rhesus macaques is marked by an increase in the proportion of Chinese ancestry at that location in a group of animals with a given disease phenotype compared with a group of animals without the disease. At the CNPRC, pure Chinese rhesus macaques are now maintained separately in one half-acre outdoor field cage and several corncribs. Historically, this was not the case. Since the early 1980s, imported Chinese founders were hybridized with Indianderived animals [Roberts et al., 2000], and hybrids now account for between 4 and 70% of the 1997 rhesus macaques currently maintained in the field cages or North cages (NCs), each housing 80–180 animals [Kanthaswamy et al., 2010]. Since pure Chinese rhesus macaques are no longer interbred with hybrid or Indian rhesus macaques at the CNPRC, the maintenance of animals with mixed ancestry has triggered a predominantly one-way gene flow of Chinese rhesus macaque alleles into the Indian rhesus gene pool. The CNPRC colony includes known hybrids of 1/8, 1/4, 3/8, 1/2, 3/4, 5/8 and 7/8 Chinese descent [Kanthaswamy et al., 2009]. Longitudinal data from 1970 to 2009 based on demographic and pedigree information illustrate that the number of hybrids have increased steadily since the early 1980s as has the frequency of private Chinese rhesus macaque short tandem repeat (STR) alleles or STR alleles unique to the Chinese rhesus macaques has increased (Fig. 1). The steep increase in private Chinese STR alleles coincides with the first introduction of Chinese founders into the colony in the mind-1980s and underscores the rate at which the genetic composition of the CNPRC rhesus colony Fig. 1. Increase in Chinese and Indian private allele (alleles unique to a population) frequencies over time at 14 STR loci. This analysis is described in the Methods section. Am. J. Primatol. is changing (Fig. 2). According to import documentation and breeding records, only 640 pure Chinese animals have been introduced into the colony. This estimate is only a fraction of the approximated census count of 17,000 Indian-derived rhesus macaques that have been reared at the colony since its establishment. Therefore, the hybrids are predominantly responsible for the introgression of Chinese alleles into the colony, especially since the practice of crossing Indian animals with Chinese imports has been discontinued. The presence of hybrids with different degrees of Chinese ancestry than F1 hybrids (Fig. 2) suggests the absence of hybrid breakdown or dysgenesis [Kanthaswamy et al., 2010]. In fact, hybridization between Chinese and Indian rhesus macaques, two regionally distinct and genetically disparate populations, has been demonstrated to result in novel highly fit hybrid phenotypes, including longer male body length, heavier male and female weight [Smith, 1986] and an impulsive aggressive temperament [Champoux et al., 1994, 1996, 1997]. These traits might influence social rank and, consequently, reproductive success (RS), because aggression is sometimes used for establishing and reinforcing social rank in rhesus macaques and high levels of aggression are observed in breeding groups during the breeding seasons when males and females compete for mating partners [Bercovitch, 1997; Lindburg, 1971]. Rhesus females typically solicit the sexual advances of males, often showing marked preferences for some males over others [Southwick et al., 1965], and the size of males is among many factors that determine a female’s choice of a mate. Body size, for example, is greater in rhesus than in longtail macaques, and is an important determinant of asymmetry of interspecies introgression from rhesus to longtail macaques in Indochina [Evans et al., 2001; Tosi et al., 2002] and might also be reflected in intraspecies hybrid rhesus mating practices. The heritability of body size and aggression has been estimated in many animal breeds, including Fig. 2. Increase in Chinese–Indian hybrids at the CNPRC over time. This analysis is also described in the Methods section. Hybrid Status and Reproductive Success / 673 rhesus macaques. An analysis by Clarke and O’Neil  showed that male Chinese-origin rhesus macaques were heavier and longer than male Indian rhesus but, as they reached adulthood, Indian adult females grew much larger than Chinese adult females. Therefore, a much greater sexual dimorphism exists between adult animals of Chinese (or hybrid) ancestry than those of Indian ancestry. If Fooden’s  and Tosi et al.’s  arguments that introgression is strongly biased in the direction of males of the larger rhesus macaques into females of smaller longtail macaques can be applied to captive rhesus macaques, then the choice of larger mating partners by female rhesus macaques may reflect female choice [Lindburg, 1971] and the larger size of the Chinese and hybrid rhesus males might enhance the RS of the smaller Indian females. Current anecdotal reports of mixed groups of hybrid and pure Indian rhesus macaques at the CNPRC imply that hybrids encounter less aggression than pure Indian animals, have priority of access to estrous females and thus might sire more offspring than pure Indian rhesus macaques. The increased siring rate of hybrids is supported by Bernstein and Gordon  who report that the rates of agonistic behavior in macaque hybrid groups are usually lower than during initial group formation. In the CNPRC scenario of mixed assemblages of Chinese and Indian rhesus macaques, it is possible that social, morphological and behavioral attributes of the hybrids contribute to their rise in the dominance hierarchy (social rank) and increased their RS, causing the asymmetric gene flow from the Chinese rhesus genome into the Indian rhesus genome at the CNPRC. Because of this, we postulate that sexual selection, either female mating preference or higher social rank of hybrids, has increased the RS of hybrids in the colony and augmented their representation in the colony. female with whom an individual animal secures maternal attention/affection as an infant. STR genotyping and parentage determination were conducted at the Veterinary Genetics Laboratory (VGL), University of California, Davis, CA. Information on STR markers, DNA extraction, PCR amplification of STRs and fragment analysis of PCR products are available elsewhere [Kanthaswamy et al., 2010]. The 14-STR genotypic dataset used for generating Figure 1 was obtained from 7,211 rhesus macaques born between 1970 and 2009. Private allele frequencies were computed using the GENEPOP software program [version 3.4; Raymond & Rousset, 1995]. Based on the allelic frequencies at the 14 STR loci, the program STRUCTURE 2.1 [Falush et al., 2003] was used to probabilistically estimate the ancestry of 7,211 rhesus macaques representing the 21 field cages including the Chinese, Indian and hybrid animals whose RS were assessed for this study (Fig. 2). The STRUCTURE analysis was run at sweeps of 103 iterations after a burn-in period of 103 without a priori defined ancestral populations. The analysis was conducted under the assumption of admixture (where samples represent a mixture of two or more ancestral groups) and correlated allele frequencies. In this analysis, when a genotype reflects hybridity, or the absence of genetic substructure, it will be assigned to one of the two subpopulations (Indian and Chinese) with probability Q, the proportion of an individual’s genome that originated from the Kth population [Falush et al., 2003; Pritchard et al., 2000]. Individuals were analyzed using this Bayesian clustering method to probabilistically assign them to a proportion of Chinese and/or Indian ancestry depending on the fraction of their genomes that originated from their ancestors. METHODS The objectives of the analysis were to assess the relative effects of hybrid status on an individual’s annual rate of reproduction at a given age (measured in years). This approach allowed us to determine not only the effects of hybrid status on lifetime RS, but also any attendant differences in maturational and reproductive trajectories. We measured hybrid status in terms of the degree of an individual’s genome that was Chinese in origin or degree of Chinese ancestry (DCA), which yielded an explanatory variable ranging from 0 (100% Indian) to 1 (100% Chinese). In addition to age and hybrid status, we also considered the effects of rank in an effort to identify how differences in DCA may actually influence RS through its effect on rank. Rank was based on the frequency of unidirectional aggression/submission behaviors within dyads and indicates an individual’s rank at a given age. We only considered individuals who could be unambiguously ranked based on The research was conducted using protocols approved by the appropriate Institutional Animal Care Committee (IACUC) and the American Society of Primatologists (ASP) Principles for the Ethical Treatment of Non Human Primates. Nuclear Genetic Analysis, Parentage Analyses and Population Genetic Analysis All demographic, behavioral, pedigree and genetic data were provided by the CNPRC. Pedigree data used in this study were verified by STR-based parentage assessments and when the genetic information was not available, parentage was assumed based on sexual activity and circumstantial evidence. This evidence includes the presence of the purported parents in the same cage during the time of conception of an individual animal and the identity of the Statistical Analyses Am. J. Primatol. 674 / Kanthaswamy et al. monthly assessments during the 2003/2009 study period. Analysis was based on 5,611 breeding events occurring between 2003 and 2009, involving 303 adult males (84 pure Indian, 214 hybrid and 5 pure Chinese males) and 1,199 adult females (326 pure Indian, 857 hybrid and 15 pure Chinese females). We modeled male and female RS separately, because male RS exhibited sixty-fold more variance than female RS. Male RS followed a Poisson distribution and was modeled as such using a log transformation. Because of the seasonality of breeding in rhesus macaques, females had, at most, one infant per year. Therefore, from a longitudinal perspective (i.e. RS/ unit of age) female RS was a binary response (0 5 no infant; 1 5 infant) and modeled using logistic regression, which assumes that the response is sampled from a binomial distribution and uses a logit link function. Model Comparison Our analytical approach was one of model comparison, using Akaike’s information criteria (AIC) [Akaike, 1974] without small sample correction. AIC provides a measure of a model’s ability to account for variance in the response variable, with smaller values indicating a better fit. In addition, we calculated Akaike weights, wi, [Burnham & Anderson, 1998] to assess the probability that a given model was the true best-fit. We present model output and weights for only those models that collectively accounted for 95% of the available Akaike weight [Burnham & Anderson, 1998]. Variance Components Our data were longitudinal—individuals were sampled multiple times over the course of their lives. As such, it was characterized by repeated measures clustered within subjects. To accommodate this clustering we adopted a hierarchical modeling approach, allowing intercepts and responses to age to vary by individual [Gelman & Hill, 2007]. We compared models accommodating only inter-individual variance in intercepts to those also including variance in slopes across age. We present the variance components of only the best-fit models here. The components of all others are available on request. All analyses were run using the freely available R software [R Development Core Team, 2008], using the ‘‘lme4’’ package [Bates et al., 2008] for the hierarchical modeling and the ‘‘bbmle’’ package [Bolker, 2010] for the model comparison. Candidate Model Set The most basic models we considered were those including only the main linear effects, individually and together, of the three explanatory variables Am. J. Primatol. (DCA, age and rank). In addition, we also included models containing a squared term for both age and DCA to accommodate possible non-linear effects, which simple plots of the data suggested may be present. In addition to the main-effects models, we also included an interaction between DCA and age, as well as interaction between their squared terms when present, because an individual’s DCA might influence its life-history. RESULTS Male RS The annual rate of male reproduction ranged from 0 to 29 offspring per year, with a mean of 2.33770.112. Model comparison (Table 1) revealed a model containing the independent effects of male rank, age and age squared to be the best-fit, with over 90% of the available model weight. The high weight of this model indicates that it can be considered the best-fit with reasonable certainty. The model predicts that male RS was a decreasing and decelerating function of increasing rank (Table 2 and Fig. 3A). In addition, it also predicts that male RS was a polynomial function of age (Table 2), with males experiencing a peak in annual reproductive output when around 11 years of age (Fig. 3B). While the top-ranked model carried over 90% of the available weight, the second-ranked carried nearly 10% and so was worth considering. This TABLE 1. Parameter Number (k), Log Likelihoods (logLik), AIC Values and Akaike Weights (wi) for Top Two Models of Male RS Model K Rank1Age1Age2 Rank1Age1Age21 DCA:Age1 DCA:Age2 7 10 Ranking 1a 2b logLik AIC wi 1,072.498 2,159 0.927 1,072.185 2,164 0.063 a Model included random intercepts for Male ID (s2 5 3.108) and random slopes for Male ID across Age (s2 5 0.042). b Model included random intercepts for Male ID (s2 5 3.126) and random slopes for Male ID across Age (s2 5 0.042). TABLE 2. Untransformed Effect Size (7Standard Error) of All Variables in First and Second-Ranked Models of Male RS Model Intercept Rank Age Age2 DCA DCA:Age DCA:Age2 First ranked 2.48770.278 0.08770.009 0.81370.056 0.03770.003 NA NA NA Second ranked 2.35870.393 0.08670.009 0.77670.079 0.03570.004 0.35570.661 0.15270.142 0.00670.008 Hybrid Status and Reproductive Success / 675 Fig. 4. Relationship between male RS and age. All lines are relationship predicted by the second-ranked model. The dotted line is the shape of the relationship when DCA 5 0, the dashed line is at the mean, DCA 5 0.421, and the solid line is at DCA 5 1. of the effects of rank stem from an association with DCA (Table 3). Female RS Fig. 3. (A) Relationship between male RS and rank, where 1 indicates an alpha male. The line is the shape of the relationship as predicted by the best-fit model (Table 2). (B) Relationship between male RS and age. The line is the shape of the relationship as predicted by the best-fit model (Table 2). model contained the same effects as the top-ranked model, as well as the additional effect of an interaction between DCA and age (Tables 1 and 2). While the standard errors for the two interaction terms caution against generalizing the effect, estimates from the model suggest that there was an effect of DCA on the maturational trajectories of males. Specifically, they suggest that an increase in DCA was associated with a later, but higher reproductive peak (Fig. 4). When transformed, the estimate of the main effect of DCA revealed that it had little or no independent effect on male RS (e 2.358–0.355 5 0.066). The fact that the estimates of the effect of rank from the 1st and 2nd ranked models were essentially the same suggests that none When modeling female RS, model comparison revealed a model containing the main effects of age, rank and DCA and an interaction between DCA and age (Table 3). As with the modeling of male RS, the high weight of this model suggests that it was the most likely best-fit within the candidate set. The model predicts that rank had a negative effect on the probability that a female had an infant in any given season (Table 4 and Fig. 5). In addition, the model predicts that this probability was also a polynomial function of age, with a reproductive peak occurring around 11–12 years of age (Fig. 6). Estimates of the interaction term in the model suggest that the timing and height of this peak varied with DCA (Table 4). Specifically, the model predicts that increase in DCA was associated with a later, but higher reproductive peak (Fig. 6). As with the modeling of male RS, however, the standard errors of interaction terms caution against over-generalizing the effect. In addition to all the effects contained by the first ranked model, the second ranked also contained a squared term for DCA and an interaction between the polynomial for age and DCA (Tables 3 and 4). Parameter estimates for the polynomial of DCA indicate that it had little bearing on female RS as a main effect (Table 4). In addition, it can be seen that standard errors for the estimates of the interaction suggest that its effect could not be reliably estimated. This, together with the model’s low weight, suggests Am. J. Primatol. 676 / Kanthaswamy et al. TABLE 3. Parameter Number (k), Log Likelihoods (logLik), AIC Values and Akaike Weights (wi) for the Top Two Models of Female RS Model K Rank1Age1 Age21DCA1 DCA:Age1DCA:Age2 Rank1Age1Age21DCA1DCA21DCA:Age1DCA:Age21DCA2:Age1DCA2:Age2 10 13 Ranking 1a 2b a logLik 2,875.692 2,875.081 AIC wi 5,771 5,776 0.903 0.083 Model included random intercepts for Male ID (s2 5 0.511) and random slopes for Male ID across Age (s2 5 0.027). Model included random intercepts for Male ID (s2 5 0.511) and random slopes for Male ID across Age (s2 5 0.027). b TABLE 4. Untransformed Effect Size (7Standard Error) of All Variables in First and Second-Ranked Models of Female RS Model Intercept Rank Age Age2 DCA DCA2 DCA:Age DCA:Age2 DCA2:Age DCA2:Age2 First ranked 3.17870.288 0.00870.002 0.86770.072 0.04270.004 0.61970.487 NA 0.16170.121 0.00370.006 NA NA Second ranked 3.20270.368 0.00870.002 0.86170.091 0.04270.005 0.38872.508 0.21172.464 0.23970.625 0.00770.034 0.08470.612 0.00470.033 Fig. 6. Relationship between female RS and age. The dotted line is the shape of the relationship when DCA 5 0, the dashed line is at the mean, DCA 5 0.421, and the solid line is at DCA 5 1. Fig. 5. Relationship between female RS and rank where 1 denotes the alpha female. The line is the shape of the relationship as predicted by the best-fit model (Table 4). that the second-ranked model offered little further insight into the factors mediating female RS beyond that described by the top-ranked model. DISCUSSION Free-ranging Indian rhesus females reach menarche by age three and can continue reproducing until about 20 years of age [Rawlins & Kessler, Am. J. Primatol. 1986]. Although after pubescence at age three or three and a half years wild rhesus males can become procreative by age four, studies reveal that males usually do not sire infants until after age eight, or after reaching full adult size [Bercovitch et al., 2003; Dixson & Nevison, 1997]. Rhesus macaques of both sexes have been observed to reach sexual maturity sooner in captivity [Catchpole & van Wagenen, 1975] and Smith  speculated that the availability of abundant food enables subadult males to achieve adult size sooner, elevate in rank more rapidly and more successfully compete with older males for access to females in captivity than in the wild. Hybrid status (DCA) was not observed to have any direct effect on either male or female RS. Interestingly, however, both male and female maturation schedules were inversely related to DCA revealed by their STR genotypes. An increase in DCA was linked with a later, but higher reproductive peak in both males and females, although the timing and height of this peak varied more conspicuously in females depending on their DCA. Indian rhesus macaques matured earlier than Chinese rhesus macaques, but the Chinese animals exhibited much higher reproductive peaks than Hybrid Status and Reproductive Success / 677 Indian animals after reaching maturity. The maturational schedules and reproductive peaks of male and female hybrids lay between the schedules and peaks of the two pure-bred forms. Smith and Scott  suggested that crossbreeding between rhesus macaques of geographically diverse origins fosters heterotic characteristics of significantly greater body length and weight in Chinese–Indian rhesus macaque hybrids. This study, however, shows that hybrids of both sexes represent intermediate fitness characteristics to either parental phenotypes in terms of maturation and reproductive peaks, which is more in line with the hybrid intermediacy hypothesis. The differences between the Chinese and Indian rhesus macaques could be attributed to how they were derived. The Indian rhesus macaques come from field cages that have been provisioned over several generations, while the Chinese animals are firstgeneration descendants of recently imported founders. Therefore, the Chinese animals, especially the females, exhibit adaptations to their cooler and drier country of origin [Clarke & O’Neil, 1999] including later maturation similar to temperate species as observed here. The relatively weak relationship between rank and RS among males suggests that dominant males were able to monopolize reproductive access to estrous females to only a limited degree. According to the priority of access (POA) model, in the seasonally breeding rhesus macaque where multiple females go into estrous simultaneously, high ranking males enjoy diminished RS because they cannot effectively restrict low ranking opponents from impregnating sexually receptive females. Because seasonal breeding fosters female choice, female rhesus macaques do not always have to choose to reproduce with top ranking males [Shively & Smith, 1985]. In a group of free-ranging rhesus macaques during one breeding season, Berard et al. [1993, 1994] observed that the highest-ranking males produced proportionally more offspring than their subordinates, and yet they were cuckolded by low ranking and extragroup males who had resorted to ‘‘furtive’’ mating tactics. Under the current housing scheme at the CNPRC, the field cages accommodate multiple sexually mature males to more closely balance the sex ratio (which increases effective population size) and better maintain group stability [Kanthaswamy et al., 2010] and seem to have made mate guarding by the dominant males quite ineffective, undermining the POA model. The inclusion of males that have achieved subadulthood in this study could have compounded the negative correlation between male rank and RS [Bercovitch, 1986], although Smith  disputed that estimates of rank-related reproductive skew are biased due to the inclusion of subadult males. The relationship between female rank and RS we observed is concordant with well-provisioned situations that preempt differential female RS resulting from the social hierarchy. This scenario also undermines the POA model with the availability of large numbers of fertile females and many subordinate and subadult males that are sexually mature. Inferences drawn from this study of 21 captive multi-male breeding groups do not support the hypothesis that DCA affords hybrid males and females a reproductive advantage. The study does, however, suggest that hybrids of all genotype classes are actively participating in the colony’s reproductive output and are thus propagating hybrid phenotypes at the CNPRC. This is concordant with present breeding strategies to promote genetic heterogeneity in the CNPRC colony [Kanthaswamy et al., 2010]. The environment in a captive colony influences rhesus macaque social structure and behavior and mating patterns differently than in natural settings. The distribution and inheritance of fitness enhancing characteristics such as early maturation, bigger body size and long reproductive span have important implications for developing the rhesus macaque as a research model under closed colony management at the CNPRC. Kanthaswamy et al. [2009, 2010] described a dynamically changing pattern of genetic diversity and hybridity within the CNPRC colony. As the rate and consequences of hybridization fluctuate with time, understanding hybrid fitness manifested in maturation and RS and its genetic basis is a crucial first step in predicting its evolutionary outcome and effectiveness of colony management of research stocks. Questions regarding the genetic impact of mixed ancestry breeding must be answered, if CNPRC researchers plan to continue to maintain hybrid populations in field cages and corncribs within the colony. ACKNOWLEDGMENTS This study was supported by the California National Primate Research Center (CNPRC) base grant (No. RR000169-48) by an ARRA supplement awarded to S. K. and Nick Lerche, CNPRC (No. RR018144-07) and NIH grants RR005090 and RR025871 to D. G. S. We are grateful to Jenny Short and Leanne Gill of the CNPRC for helpful discussions that facilitated this manuscript. We thank Mark Grote (Anthropology, UC Davis) for his helpful advice on the statistics. These animals were managed in compliance with Institutional Animal Care and Use Committee (IACUC) regulations or in accordance with the National Institutes of Health guidelines or the US Department of Agriculture regulations prescribing the humane care and use of laboratory animals. REFERENCES Akaike H. 1974. 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