Effect of outbreeding on weight and growth rate of captive infant rhesus macaques

The introduction of unrelated conspecifics into captive groups of primate species is desirable to inhibit inbreeding. However, for many species, such groups increasingly represent highly inbred isolate populations that are analogous to regionally isolated populations of the same species among whom the effects of outcrossing on fitness are unknown. A study of potentially adverse effects of cross-breeding between regionally isolated populations of rhesus macaques was conducted to assess the maximum advantage or disadvantage to be expected for cross-breeding such populations of other cercopithecoid primates. For this purpose, the infant weights and rates of growth of hybrid Chinese/Indian rhesus macaques were compared to those of their nonhybrid Indian peers and to those of consanguineously inbred Indian rhesus macaques from several other captive breeding groups. Neither adverse nor advantageous effects of such hybridization were detected, suggesting that outcrossing between isolates of other cercopithecoid primates with a similar social structure and mating pattern should not affect the fitness of resulting offspring. Since levels of inbreeding are roughly inversely proportional to levels of genetic diversity within populations, such outcrossing should be intensified by zoos and other captive breeding centers to ensure the continued survival of captive species, especially those that are endangered or otherwise irreplaceable.     

Development of a Chinese-Indian hybrid (Chindian) rhesus macaque colony at the California National Primate Research Center by introgression

Background  Fullbred Chinese and Indian rhesus macaques represent genetically distinct populations. The California National Primate Research Center introduced Chinese founders into its Indian-derived rhesus colony in response to the 1978 Indian embargo on exportation of animals for research and the concern that loss of genetic variation in the closed colony would hamper research efforts. The resulting hybrid rhesus now number well over a thousand animals and represent a growing proportion of the animals in the colony.
Methods  We characterized the population genetic structure of the hybrid colony and compared it with that of their pure Indian and Chinese progenitors.
Results  The hybrid population contains higher genetic diversity and linkage disequilibrium than their full Indian progenitors and represents a resource with unique research applications.
Conclusions  The genetic diversity of the hybrids indicates that the strategy to introduce novel genes into the colony by hybridizing Chinese founders and their hybrid offspring with Indian-derived animals was successful.     

A Large‐Scale SNP‐Based Genomic Admixture Analysis of the Captive Rhesus Macaque Colony at the California National Primate Research Center

Some breeding facilities in the United States have crossbred Chinese and Indian rhesus macaque (Macaca mulatta) founders either purposefully or inadvertently. Genetic variation that reflects geographic origins among research subjects has the potential to influence experimental outcomes. The use of animals from different geographic regions, their hybrids, and animals of varying degrees of kinship in an experiment can obscure treatment effects under study because high interanimal genetic variance can increase phenotypic variance among the research subjects. The intent of this study, based on a broad genomic analysis of 2,808 single nucleotide polymorphisms (SNPs), is to ensure that only animals estimated to be of pure Indian or Chinese ancestry, based on both demographic and genetic information, are used as sources of infants for derivation and expansion of the California National Primate Research Center's (CNPRC) super‐Specific Pathogen Free (SSPF) rhesus macaque colony. Studies of short tandem repeats (STRs) in Indian and Chinese rhesus macaques have reported that heterozygosity of STRs is higher in Chinese rhesus macaques than in Indian rhesus macaques. The present study shows that heterozygosity of SNPs is actually higher in Indian than in Chinese rhesus macaques and that the Chinese SSPF rhesus macaque colony is far less differentiated from their founders compared to the Indian‐origin animals. The results also reveal no evidence of recent gene flow from long‐tailed and pig‐tailed macaques into the source populations of the SSPF rhesus macaques. This study indicates that many of the long‐tailed macaques held in the CNPRC are closely related individuals. Most polymorphisms shared among the captive rhesus, long‐tailed, and pig‐tailed macaques likely predate the divergence among these groups. Am. J. Primatol. 74:747‐757, 2012. © 2012 Wiley Periodicals, Inc.     

Genetic characterization of wild and captive rhesus macaques in China

The genetic structures of wild and captive rhesus macaque populations within China were compared by analyzing the mtDNA sequences of 203 captive-bred Chinese rhesus macaques with 77 GenBank sequences from wild-caught animals trapped throughout China. The genotypes of 22 microsatellites of captive Chinese rhesus macaques were also compared with those of captive Indian animals. The Chinese population is significantly differentiated from the Indian population and is more heterogeneous. Thus, compared with Indian rhesus macaques the phenotypic variance of traits with high heritability will be inflated in Chinese animals. Our data suggest that the western Chinese provinces have more subdivided populations than the eastern and southern Chinese provinces. The southern Chinese populations are the least structured and might have been more recently established. Human-mediated interbreeding among captive Chinese populations has occurred, implying that Chinese breeding strategies can influence the interpretation of biomedical research in the USA.     

4040 SNPs for genomic analysis in the rhesus macaque (Macaca mulatta)

Although the rhesus macaque (Macaca mulatta) is commonly used for biomedical research and becoming a preferred model for translational medicine, quantification of genome-wide variation has been slow to follow the publication of the genome in 2007. Here we report the properties of 4040 single nucleotide polymorphisms discovered and validated in Chinese and Indian rhesus macaques from captive breeding colonies in the United States. Frequency-matched measures of linkage disequilibrium were much greater in the Indian sample. Although the majority of polymorphisms were shared between the two populations, rare alleles were over twice as common in the Chinese sample. Indian rhesus had higher rates of heterozygosity, as well as previously undetected substructure, potentially due to admixture from Burma in wild populations and demographic events post-captivity.     

Identification of Country of Origin and Admixture Between Indian and Chinese Rhesus Macaques

We describe a restriction analysis that distinguishes between rhesus macaques of unmixed Indian and Chinese ancestry and between western and eastern Chinese ancestry. We amplified a 254-bp fragment of mitochondrial DNA (mtDNA) that contains restriction sites hypothesized to be diagnostic of country of origin for samples from 534 and 567 individuals alleged to be of solely Indian or solely Chinese origin, respectively. After digestion with the MaeIII, SmlI, and BccI restriction enzymes, the polymerase chain reaction (PCR) products of only 3 of the 1101 samples exhibited restriction patterns uncharacteristic of their alleged country of origin. A sample comprising 392 of these rhesus macaques was genotyped for 24 nuclear microsatellite (STR) loci. Principal coordinates analysis confirmed marked genetic similarity of regional populations within each country but a substantial difference between Indian and Chinese rhesus macaques. Using STRUCTURE (Pritchard and Wen, 2003),we assigned probabilities of Chinese and Indian ancestry to each sample based on its STR genotypes. We assigned all the unmixed rhesus macaques to their correct countries of origin with probabilities >0.95. We constructed an artificial sample of 1st-generation hybrid Indian/Chinese rhesus macaques by randomly sampling from the genotypes of Indian and Chinese individuals. STRUCTURE assigned robabilities of Chinese and Indian ancestry to hybrids that closely corresponded with the proportions of alleles in that sample drawn from unmixed Chinese and Indian rhesus macaques.     

Do Leptin Levels Predict Weight Gain?—A 5-Year Follow-Up Study in Mauritius

Objective : To investigate whether relative baseline leptin levels predict long-term changes in adiposity and/or its distribution. Research Methods and Procedures : In a longitudinal study of 2888 nondiabetic Mauritians aged 25 years to 74 years who participated in population-based surveys in 1987 and 1992, changes in body mass index (BMI), waist/hip ratio (WHR), and waist circumference were compared between “hyperleptinemic,” “normoleptinemic,” and “hypoleptinemic” groups. “Relative leptin levels” were calculated as standardized residuals from the regression of log₁₀ leptin on baseline BMI to provide a leptin measure independent of BMI. Analyses were performed within each sex. A linear regression model was used to assess the effect of standardized residuals on changes in BMI, WHR, and waist circumference, independent of baseline BMI, age, fasting insulin, and ethnicity. Results : After adjusting for age and baseline BMI by analysis of covariance, there was no difference in changes in BMI, WHR, or waist circumference between men with low, normal, or high relative leptin levels. Among women, there was a significant difference in ΔWHR across leptin groups, such that the largest increase occurred in the “normal” leptin group. For both men and women, the linear regression models explained ?10% of variation in dependent variables, and the only significant independent variables were age, BMI, and being of Chinese origin, compared with Indian origin. Discussion : These findings do not support a role for leptin concentration in predicting weight gain or changes in fat distribution in adults over a 5-year period.     

Changes in blood chemistry and hematology variables during aging in captive rhesus macaques (Macaca mulatta)

Identifying changes with age in physiological variables of captive nonhuman primates will aid in the proper treatment and clinical diagnosis of these animals, as well as enhance our understanding of nonhuman primate models for human aging. Information for 33 physiological variables was obtained from the Primate Aging Database, a multi-centered database being developed for clinical and research use. Using multiple regression analyses, we investigated the relationship of age to hematological variables, blood chemistry and body weight in 345 captive rhesus monkeys (age range 7-30 years) from three different primate research facilities. The analyses revealed that 15 of these variables show a significant relationship with chronological age and are altered in older as compared with adult animals. Here we present the first phase of a project that will: a) identify changes with age in physiological variables among adult captive rhesus macaques; and b) characterize normative values for the aging rhesus population.     

Haldane's rule revisited: do hybrid females have a shorter lifespan? Survival of hybrids in a recent contact zone between two large gull species

Haldane's rule predicts that particularly high fitness reduction should affect the heterogametic sex of interspecific hybrids. Despite the fact that hybridization is widespread in birds, survival of hybrid individuals is rarely addressed in studies of avian hybrid zones, possibly because of methodological constraints. Here, having applied capture–mark–recapture models to an extensive, 19‐year‐long data set on individually marked birds, we estimate annual survival rates of hybrid individuals in the hybrid zone between herring (Larus argentatus) and Caspian (Larus cachinnans) gulls. In both parental species, males have a slightly higher survival rate than females (model‐weighted mean ± SE: herring gull males 0.88 ± 0.01, females 0.87 ± 0.01, Caspian gull males 0.88 ± 0.01, females 0.87 ± 0.01). Hybrid males do not survive for a shorter time than nonhybrid ones (0.88 ± 0.01), whereas hybrid females have the lowest survival rate among all groups of individuals (0.83 ± 0.03). This translates to a shorter adult (reproductive) lifespan (on average by 1.7–1.8 years, i.e. ca 25%) compared with nonhybrid females. We conclude that, in line with Haldane's rule, the lower survival rate of female hybrids may contribute to selection against hybrids in this hybrid zone.     

Absence of deleterious effects of inbreeding in rhesus macaques

The limited availability of rhesus macaques through importation and the need for large numbers of them for use in biomedical research in this country have led to large- scale efforts to breed them domestically in captive groups. Since gene flow into the groups is usually restricted, consanguineous inbreeding can lead to inbreeding depression, which is characterized by increases in mortality, declines in fertility, and reductions in traits associated with physiological efficiency. For this reason, it is desirable to determine the level of inbreeding at which inbreeding depression occurs in rhesus macaques. I compared fertility, mortality, and the rate of weight gain in inbred and noninbred rhesus monkeys in three captive groups. There is no evidence of inbreeding depression in rhesus macaques whose inbreeding coefficients are ≤ 0.125, a level at which inbreeding depression is known to occur in some species.     

A comparison of the demographic structure and growth of free-ranging and captive groups of rhesus monkeys (Macaca mulatta)

Vital statistics are employed to estimate rates of mortality, fetility and growth for a group of about 450 captive rhesus monkeys housed in six separate enclosures at the California Primate Research Center (CPRC). These rates were compared with those previously reported for a free-ranging group of rhesus monkeys. Relative to the free-ranging group, the CPRC monkeys experienced higher fertility below age 5 and lower mortality beyond age 3. These rates are associated with a potential intrinsic rate of increase of about 10%, a rate which is about 50% higher than that for the free-ranging group. Reasons for this marked difference in reproductive success of the two groups are discussed.     

Sibling competition arena: selfing and a competition arena can combine to constitute a barrier to gene flow in sympatry

Closely related species coexisting in sympatry provide critical insight into the mechanisms underlying speciation and the maintenance of genetic divergence. Selfing may promote reproductive isolation by facilitating local adaptation, causing reduced hybrid fitness in parental environments. Here, we propose a novel mechanism by which selfing can further impair interspecific gene flow: selfing may act to ensure that nonhybrid progeny systematically co-occur whenever hybrid genotypes are produced. Under a competition arena, the fitness differentials between nonhybrid and hybrid progeny are then magnified, preventing development of interspecific hybrids. We investigate whether this "sibling competition arena" can explain the coexistence in sympatry of closely related species of the plant fungal pathogens (Microbotryum) causing anther-smut disease. The probabilities of intrapromycelial mating (automixis), outcrossing, and sibling competition were manipulated in artificial inoculations to evaluate their contribution to reproductive isolation. We report that both intrapromycelial selfing and sibling competition significantly reduced rates of hybrid infection beyond that expected based solely upon selfing rates and noncompetitive fitness differentials between hybrid and nonhybrid progeny. Our results thus suggest that selfing and a sibling competition arena can combine to constitute a barrier to gene flow and diminish selection for additional barriers to gene flow in sympatry.     

Growth retardation in premenarchial female rhesus monkeys during chronic administration of a GnRH agonist (leuprolide acetate)

Abstract: Leuprolide acetate in depot form (0.75 mg/kg body weight/month, im) was administered to four female rhesus monkeys from 18–30 months of age, a period that includes the premenarchial growth spurt. They were compared to eight age matched controls. As anticipated, sexual maturation was blocked in the Leuprolide group and menarche did not occur. Growth was also severely retarded; no weight gain occurred during the study in the Leuprolide group as compared to a 25% weight gain (P = .004) in the control group. The Leuprolide group also lost muscle mass. Food intake normalized for body weight was not affected. Linear growth averaged 35% less in the Leuprolide group. Serum IGF-1 concentrations increased from 486±84 to 965±47 ng/mL (P = .0025) in the Leuprolide group and from 838±139 to 3,006±545 ng/mL (P = .0016) in the control group. These data suggest that premenarchial pituitary/gonadal suppression results in a distinctive pattern of growth retardation in monkeys.     

Body fat,rank, and nutritional status in a captive group of Rhesus Macaques

Using weight and skinfold thickness to calculate relative body fat, the fat content of 21 captive female rhesus macaques was estimated. Although age and. pregnancy had no effect on fat, rank was significant, especially during winter, with high-rank females having the highest fat scores. Rank therefore has a significant effect on the health of captive animals and may also affect the health of individuals in feral groups.     

Diversity in commercial varieties and landraces of black eggplants and implications for broadening the breeders' gene pool

Black‐coloured eggplants (Solanum melongena) represent the commercially most important group of eggplants in Europe and North America. Most of the modern varieties of black eggplants correspond to F₁ hybrids, which at the same time constitute an elite gene pool for the development of new varieties. However, there are many black landraces and old varieties, which could be useful as sources of variation for black eggplant breeding programmes as well as for the broadening of the genetic diversity of the breeders’ gene pool. We have studied the morphological and molecular [amplified fragment length polymorphism and simple sequence repeat (SSR)] diversity in a collection of 38 black eggplant accessions, including commercial (modern F₁ hybrid and old nonhybrid) varieties and landraces as well as in six nonblack control eggplants, from different origins. The results show that black eggplants contain a considerable morphological and molecular diversity, but commercial varieties, and in particular F₁ hybrids, display a reduced morphological and molecular diversity when compared with landraces. The principal components analysis morphological and principal coordinates analysis molecular analyses show that commercial F₁ hybrids group together, indicating that they share a common and narrow gene pool. Commercial F₁ hybrids present a series of productive advantages, like early production, intense black colour (low L*, a* and b*) values and absence of fruit calyx prickles. However, several of the landraces and old nonhybrid varieties studied present a high yield as well as other traits of interest for eggplant breeding. Furthermore, given the low genetic diversity of F₁ hybrids and the moderate level of SSR heterozygosity found in these materials (0.382), introduction of black landraces and old varieties in the present breeding programmes could contribute to broadening the gene pool used by breeders and this could help increase the heterosis for yield of F₁ hybrids, which is greatly favoured by high heterozygosity levels.     

Pubertal weight gain in female rhesus macaques

In order to describe the timing and extent of accelerated pubertal weight gain in female rhesus, we examined a large colony data base consisting of over 10,000 weight records for animals between 1.5 and 3.0 years of age (menarche occurs at about 2.6 years). Average colony weights were determined by week of age from information on age at weighing. Cross-sectional analyses with linear regression demonstrated an acceleration in weight increase from 196 to 231 weeks (28–33 months) when colony weights increased 381 g/12 weeks as opposed to an average of 193 and 203 g, respectively, during the preceding and succeeding age intervals of the same length. Longitudinal analyses (n = 428) indicated that maximum individual growth velocity averaged 499 ± 18 g/12 weeks and occurred at 119 ± 5.6 weeks (29.7 ± 0.2 months) of age. Nonlinear modeling with the Gompertz function indicated that decelerating growth rates seen at earlier ages were not characteristic of the period of accelerated pubertal growth. © 1996 Wiley-Liss, Inc.     

Behavioural isolation may facilitate homoploid hybrid speciation in cichlid fish

Hybrid speciation is constrained by the homogenizing effects of gene flow from the parental species. In the absence of post‐mating isolation due to structural changes in the genome, or temporal or spatial premating isolation, another form of reproductive isolation would be needed for homoploid hybrid speciation to occur. Here, we investigate the potential of behavioural mate choice to generate assortative mating among hybrids and parental species. We made three‐first‐generation hybrid crosses between different species of African cichlid fish. In three‐way mate‐choice experiments, we allowed hybrid and nonhybrid females to mate with either hybrid or nonhybrid males. We found that hybrids generally mated nonrandomly and that hybridization can lead to the expression of new combinations of traits and preferences that behaviourally isolate hybrids from both parental species. Specifically, we find that the phenotypic distinctiveness of hybrids predicts the symmetry and extent of their reproductive isolation. Our data suggest that behavioural mate choice among hybrids may facilitate the establishment of isolated hybrid populations, even in proximity to one or both parental species.     

Heterosis associated with regional crossbreeding between captive groups of rhesus macaques

The lengths and weights of male and female Chinese-Indian hybrid rhesus macaques were compared with those of age- and sex-matched non-hybrid (Indian) controls to assess the occurrence of heterosis (hybrid vigor). Hybrid males and females had higher average, age-adjusted values of weight than nonhybrids. Hybrid males, but not females, also had a higher average, age-adjusted length than nonhybrids. These results are consistent with the hypothesis that regional crossbreeding of rhesus monkeys fosters heterosis.     

Identification of MHC class I sequences in Chinese-origin rhesus macaques

The rhesus macaque (Macaca mulatta) is an excellent model for human disease and vaccine research. Two populations exhibiting distinctive morphological and physiological characteristics, Indian- and Chinese-origin rhesus macaques, are commonly used in research. Genetic analysis has focused on the Indian macaque population, but the accessibility of these animals for research is limited. Due to their greater availability, Chinese rhesus macaques are now being used more frequently, particularly in vaccine and biodefense studies, although relatively little is known about their immunogenetics. In this study, we discovered major histocompatibility complex (MHC) class I cDNAs in 12 Chinese rhesus macaques and detected 41 distinct Mamu-A and Mamu-B sequences. Twenty-seven of these class I cDNAs were novel, while six and eight of these sequences were previously reported in Chinese and Indian rhesus macaques, respectively. We then performed microsatellite analysis on DNA from these 12 animals, as well as an additional 18 animals, and developed sequence specific primer PCR (PCR-SSP) assays for eight cDNAs found in multiple animals. We also examined our cohort for potential admixture of Chinese and Indian origin animals using a recently developed panel of single nucleotide polymorphisms (SNPs). The discovery of 27 novel MHC class I sequences in this analysis underscores the genetic diversity of Chinese rhesus macaques and contributes reagents that will be valuable for studying cellular immunology in this population.     

Effects of geographic origin on captive Macaca mulatta mitochondrial DNA variation

Partial sequences from mitochondrial (mt) 12S and 16S rRNA genes were analyzed to characterize diversity among captive rhesus macaques (Macaca mulatta) originating from various geographic regions. Several nested clades, defined by closely related haplotypes, were identified, suggesting considerable genetic subdivision, probably relics from heterogeneous origins, founder effects, and genetic drift, followed by breeding isolation. The rhesus matrilineages from India differed discretely and markedly from Chinese matrilineages; approximately 90% of the genetic heterogeneity among the combined samples of Indian and Chinese rhesus macaques studied here was due to country of origin. In addition, mtDNA sequences from macaques of China were more diverse than those from rhesus macaques of India, an outcome consistent with China's greater subspecies diversity and with nuclear genotype distributions. Otherwise, the distribution of mtDNA variation within rhesus macaques of China, and especially within those of India, exhibited far less structure and did not conform to a simple isolation-by-distance model. As the demand for genetically heterogeneous and well-characterized rhesus macaques for biomedical-based research increases, mtDNA haplotypes can be useful for genetically defining, preserving maximal levels of genetic diversity within, and confirming the geographic origin of captive breeding groups of rhesus macaques.