Quantitative trait locus analysis of stage-specific inbreeding depression in the Pacific oyster Crassostrea gigas

Inbreeding depression and genetic load have been widely observed, but their genetic basis and effects on fitness during the life cycle remain poorly understood, especially for marine animals with high fecundity and high, early mortality (type-III survivorship). A high load of recessive mutations was previously inferred for the Pacific oyster Crassostrea gigas, from massive distortions of zygotic, marker segregation ratios in F(2) families. However, the number, genomic location, and stage-specific onset of mutations affecting viability have not been thoroughly investigated. Here, we again report massive distortions of microsatellite-marker segregation ratios in two F(2) hybrid families, but we now locate the causative deleterious mutations, using a quantitative trait locus (QTL) interval-mapping model, and we characterize their mode of gene action. We find 14-15 viability QTL (vQTL) in the two families. Genotypic frequencies at vQTL generally suggest selection against recessive or partially recessive alleles, supporting the dominance theory of inbreeding depression. No epistasis was detected among vQTL, so unlinked vQTL presumably have independent effects on survival. For the first time, we track segregation ratios of vQTL-linked markers through the life cycle, to determine their stage-specific expression. Almost all vQTL are absent in the earliest life stages examined, confirming zygotic viability selection; vQTL are predominantly expressed before the juvenile stage (90%), mostly at metamorphosis (50%). We estimate that, altogether, selection on vQTL caused 96% mortality in these families, accounting for nearly all of the actual mortality. Thus, genetic load causes substantial mortality in inbred Pacific oysters, particularly during metamorphosis, a critical developmental transition warranting further investigation.     

Recent approaches into the genetic basis of inbreeding depression in plants

Predictions for the evolution of mating systems and genetic load vary, depending on the genetic basis of inbreeding depression (dominance versus overdominance, epistasis and the relative frequencies of genes of large and small effect). A distinction between the dominance and overdominance hypotheses is that deleterious recessive mutations should be purged in inbreeding populations. Comparative studies of populations differing in their level of inbreeding and experimental approaches that allow selection among inbred lines support this prediction. More direct biometric approaches provide strong support for the importance of partly recessive deleterious alleles. Investigators using molecular markers to study quantitative trait loci (QTL) often find support for overdominance, though pseudo-overdominance (deleterious alleles linked in repulsion) may bias this perception. QTL and biometric studies of inbred lines often find evidence for epistasis, which may also contribute to the perception of overdominance, though this may be because of the divergent lines initially crossed in QTL studies. Studies of marker segregation distortion commonly uncover genes of major effect on viability, but these have only minor contributions to inbreeding depression. Although considerable progress has been made in understanding the genetic basis of inbreeding depression, we feel that all three aspects merit more study in natural plant populations.     

Joint effects of self-fertilization and population structure on mutation load, inbreeding depression and heterosis

Both the spatial distribution of organisms and their mode of reproduction have important effects on the change in allele frequencies within populations. In this article, we study the combined effect of population structure and the rate of partial selfing of organisms on the efficiency of selection against recurrent deleterious mutations. Assuming an island model of population structure and weak selection, we express the mutation load, the within- and between-deme inbreeding depression, and heterosis as functions of the frequency of deleterious mutants in the metapopulation; we then use a diffusion model to calculate an expression for the equilibrium probability distribution of this frequency of deleterious mutants. This allows us to derive approximations for the average mutant frequency, mutation load, inbreeding depression, and heterosis, the simplest ones being Equations 35-39 in the text. We find that population structure can help to purge recessive deleterious mutations and reduce the load for some parameter values (in particular when the dominance coefficient of these mutations is <0.2-0.3), but that this effect is reversed when the selfing rate is above a given value. Conversely, within-deme inbreeding depression always decreases, while heterosis always increases, with the degree of population subdivision, for all selfing rates.     

Effects of Interference Between Selected Loci on the Mutation Load,Inbreeding Depression,and Heterosis

A classical prediction from single-locus models is that inbreeding increases the efficiency of selection against partially recessive deleterious alleles (purging), thereby decreasing the mutation load and level of inbreeding depression. However, previous multilocus simulation studies found that increasing the rate of self-fertilization of individuals may not lead to purging and argued that selective interference among loci causes this effect. In this article, I derive simple analytical approximations for the mutation load and inbreeding depression, taking into account the effects of interference between pairs of loci. I consider two classical scenarios of nonrandomly mating populations: a single population undergoing partial selfing and a subdivided population with limited dispersal. In the first case, correlations in homozygosity between loci tend to reduce mean fitness and increase inbreeding depression. These effects are stronger when deleterious alleles are more recessive, but only weakly depend on the strength of selection against deleterious alleles and on recombination rates. In subdivided populations, interference increases inbreeding depression within demes, but decreases heterosis between demes. Comparisons with multilocus, individual-based simulations show that these analytical approximations are accurate as long as the effects of interference stay moderate, but fail for high deleterious mutation rates and low dominance coefficients of deleterious alleles.     

Inbreeding load, average dominance and the mutation rate for mildly deleterious alleles in Mimulus guttatus

The goal of this study is to provide information on the genetics of inbreeding depression in a primarily outcrossing population of Mimulus guttatus. Previous studies of this population indicate that there is tremendous inbreeding depression for nearly every fitness component and that almost all of this inbreeding depression is due to mildly deleterious alleles rather than recessive lethals or steriles. In this article I assayed the homozygous and heterozygous fitnesses of 184 highly inbred lines extracted from a natural population. Natural selection during the five generations of selfing involved in line formation essentially eliminated major deleterious alleles but was ineffective in purging alleles with minor fitness effects and did not appreciably diminish overall levels of inbreeding depression. Estimates of the average degree of dominance of these mildly deleterious alleles, obtained from the regression of heterozygous fitness on the sum of parental homozygous fitness, indicate that the detrimental alleles are partially recessive for most fitness traits, with h approximately 0.15 for cumulative measures of fitness. The inbreeding load, B, for total fitness is approximately 1.0 in this experiment. These results are consistent with the hypothesis that spontaneous mildly deleterious mutations occur at a rate >0.1 mutation per genome per generation.     

Inbreeding uncovers fundamental differences in the genetic load affecting male and female fertility in a butterfly

Inbreeding depression is most pronounced for traits closely associated with fitness. The traditional explanation is that natural selection eliminates deleterious mutations with additive or dominant effects more effectively than recessive mutations, leading to directional dominance for traits subject to strong directional selection. Here we report the unexpected finding that, in the butterfly Bicyclus anynana, male sterility contributes disproportionately to inbreeding depression for fitness (complete sterility in about half the sons from brother-sister matings), while female fertility is insensitive to inbreeding. The contrast between the sexes for functionally equivalent traits is inconsistent with standard selection arguments, and suggests that trait-specific developmental properties and cryptic selection play crucial roles in shaping genetic architecture. There is evidence that spermatogenesis is less developmentally stable than oogenesis, though the unusually high male fertility load in B. anynana additionally suggests the operation of complex selection maintaining male sterility recessives. Analysis of the precise causes of inbreeding depression will be needed to generate a model that reliably explains variation in directional dominance and reconciles the gap between observed and expected genetic loads carried by populations. This challenging evolutionary puzzle should stimulate work on the occurrence and causes of sex differences in fertility load.     

Environmental stress increases selection against and dominance of deleterious mutations in inbred families of the Pacific oyster Crassostrea gigas

The deleterious effects of inbreeding are well documented and of major concern in conservation biology. Stressful environments have generally been shown to increase inbreeding depression; however, little is known about the underlying genetic mechanisms of the inbreeding-by-stress interaction and to what extent the fitness of individual deleterious mutations is altered under stress. Using microsatellite marker segregation data and quantitative trait locus (QTL) mapping methods, I performed a genome scan for deleterious mutations affecting viability (viability or vQTL) in two inbred families of the Pacific oyster Crassostrea gigas, reared in a stressful, nutrient-poor diet and a favourable, nutrient-rich diet, which had significant effects on growth and survival. Twice as many vQTL were detected in the stressful diet compared with the favourable diet, resulting primarily from substantially greater mortality of homozygous genotypes. At vQTL, estimates of selection (s) and dominance (h) were greater in the stressful environment (= 0.86 vs. 0.54 and = 0.35 vs. 0.18, in stressful and nonstressful diets, respectively). There was no evidence of interaction between vQTL. Individual vQTL differed across diets in selection only, or in both selection and dominance, and some vQTL were not affected by diet. These results suggest that stress-associated increases in selection against individual deleterious alleles underlie greater inbreeding depression with stress. Furthermore, the finding that inbreeding-by-environment interaction appears, to some extent, to be locus specific, helps to explain previous observations of lineage-specific expression of inbreeding depression and environment-specific purging, which have important implications for conservation and evolutionary biology.     

Efficiency of selection, as measured by single nucleotide polymorphism variation, is dependent on inbreeding rate in Drosophila melanogaster

It is often hypothesized that slow inbreeding causes less inbreeding depression than fast inbreeding at the same absolute level of inbreeding. Possible explanations for this phenomenon include the more efficient purging of deleterious alleles and more efficient selection for heterozygote individuals during slow, when compared with fast, inbreeding. We studied the impact of inbreeding rate on the loss of heterozygosity and on morphological traits in Drosophila melanogaster. We analysed five noninbred control lines, 10 fast inbred lines and 10 slow inbred lines; the inbred lines all had an expected inbreeding coefficient of approximately 0.25. Forty single nucleotide polymorphisms in DNA coding regions were genotyped, and we measured the size and shape of wings and counted the number of sternopleural bristles on the genotyped individuals. We found a significantly higher level of genetic variation in the slow inbred lines than in the fast inbred lines. This higher genetic variation was resulting from a large contribution from a few loci and a smaller effect from several loci. We attributed the increased heterozygosity in the slow inbred lines to the favouring of heterozygous individuals over homozygous individuals by natural selection, either by associative over‐dominance or balancing selection, or a combination of both. Furthermore, we found a significant polynomial correlation between genetic variance and wing size and shape in the fast inbred lines. This was caused by a greater number of homozygous individuals among the fast inbred lines with small, narrow wings, which indicated inbreeding depression. Our results demonstrated that the same amount of inbreeding can have different effects on genetic variance depending on the inbreeding rate, with slow inbreeding leading to higher genetic variance than fast inbreeding. These results increase our understanding of the genetic basis of the common observation that slow inbred lines express less inbreeding depression than fast inbred lines. In addition, this has more general implications for the importance of selection in maintaining genetic variation.     

Long-term exhaustion of the inbreeding load in Drosophila melanogaster

Inbreeding depression, the decline in fitness of inbred individuals, is a ubiquitous phenomenon of great relevance in evolutionary biology and in the fields of animal and plant breeding and conservation. Inbreeding depression is due to the expression of recessive deleterious alleles that are concealed in heterozygous state in noninbred individuals, the so-called inbreeding load. Genetic purging reduces inbreeding depression by removing these alleles when expressed in homozygosis due to inbreeding. It is generally thought that fast inbreeding (such as that generated by full-sib mating lines) removes only highly deleterious recessive alleles, while slow inbreeding can also remove mildly deleterious ones. However, a question remains regarding which proportion of the inbreeding load can be removed by purging under slow inbreeding in moderately large populations. We report results of two long-term slow inbreeding Drosophila experiments (125–234 generations), each using a large population and a number of derived lines with effective sizes about 1000 and 50, respectively. The inbreeding load was virtually exhausted after more than one hundred generations in large populations and between a few tens and over one hundred generations in the lines. This result is not expected from genetic drift alone, and is in agreement with the theoretical purging predictions. Computer simulations suggest that these results are consistent with a model of relatively few deleterious mutations of large homozygous effects and partially recessive gene action.Subject terms: Quantitative trait, Inbreeding     

Overdominant epistatic loci are the primary genetic basis of inbreeding depression and heterosis in rice. I. Biomass and grain yield

To understand the genetic basis of inbreeding depression and heterosis in rice, main-effect and epistatic QTL associated with inbreeding depression and heterosis for grain yield and biomass in five related rice mapping populations were investigated using a complete RFLP linkage map of 182 markers, replicated phenotyping experiments, and the mixed model approach. The mapping populations included 254 F(10) recombinant inbred lines derived from a cross between Lemont (japonica) and Teqing (indica) and two BC and two testcross hybrid populations derived from crosses between the RILs and their parents plus two testers (Zhong 413 and IR64). For both BY and GY, there was significant inbreeding depression detected in the RI population and a high level of heterosis in each of the BC and testcross hybrid populations. The mean performance of the BC or testcross hybrids was largely determined by their heterosis measurements. The hybrid breakdown (part of inbreeding depression) values of individual RILs were negatively associated with the heterosis measurements of their BC or testcross hybrids, indicating the partial genetic overlap of genes causing hybrid breakdown and heterosis in rice. A large number of epistatic QTL pairs and a few main-effect QTL were identified, which were responsible for >65% of the phenotypic variation of BY and GY in each of the populations with the former explaining a much greater portion of the variation. Two conclusions concerning the loci associated with inbreeding depression and heterosis in rice were reached from our results. First, most QTL associated with inbreeding depression and heterosis in rice appeared to be involved in epistasis. Second, most ( approximately 90%) QTL contributing to heterosis appeared to be overdominant. These observations tend to implicate epistasis and overdominance, rather than dominance, as the major genetic basis of heterosis in rice. The implications of our results in rice evolution and improvement are discussed.     

Heterosis is common and inbreeding depression absent in natural populations of Arabidopsis thaliana

The importance of genetic drift in shaping patterns of adaptive genetic variation in nature is poorly known. Genetic drift should drive partially recessive deleterious mutations to high frequency, and inter‐population crosses may therefore exhibit heterosis (increased fitness relative to intra‐population crosses). Low genetic diversity and greater genetic distance between populations should increase the magnitude of heterosis. Moreover, drift and selection should remove strongly deleterious recessive alleles from individual populations, resulting in reduced inbreeding depression. To estimate heterosis, we crossed 90 independent line pairs of Arabidopsis thaliana from 15 pairs of natural populations sampled across Fennoscandia and crossed an additional 41 line pairs from a subset of four of these populations to estimate inbreeding depression. We measured lifetime fitness of crosses relative to parents in a large outdoor common garden (8,448 plants in total) in central Sweden. To examine the effects of genetic diversity and genetic distance on heterosis, we genotyped parental lines for 869 SNPs. Overall, genetic variation within populations was low (median expected heterozygosity = 0.02), and genetic differentiation was high (median F_ST = 0.82). Crosses between 10 of 15 population pairs exhibited significant heterosis, with magnitudes of heterosis as high as 117%. We found no significant inbreeding depression, suggesting that the observed heterosis is due to fixation of mildly deleterious alleles within populations. Widespread and substantial heterosis indicates an important role for drift in shaping genetic variation, but there was no significant relationship between fitness of crosses relative to parents and genetic diversity or genetic distance between populations.     

Genetic load,inbreeding depression and heterosis in an age‐structured metapopulation

In a metapopulation, the process of recurrent local extinction and recolonization gives rise to an age structure among demes. Recently established demes will tend to differ from older demes in terms of the levels of genetic diversity found within them and the way this diversity is distributed among demes in the same and different ages. The effects of population turnover on average levels of genetic diversity among demes in a metapopulation have been the focus of much attention, both for neutral and nonneutral loci, but much less is known about the distribution of nonneutral genetic diversity among demes of different ages. In this paper, we used computer simulations to study the distribution of genetic load, inbreeding depression and heterosis in an age‐structured metapopulation. We found that, for mildly deleterious mutations, within‐deme inbreeding depression increased, whereas heterosis and genetic load decreased with deme age following severe colonization bottlenecks. In contrast, recessive lethal alleles tended to be purged during colonization, with older populations showing higher genetic load and higher within‐deme inbreeding depression. Heterosis caused by recessive lethal alleles and resulting from gene flow among different demes tended to be greatest for young demes, because the mutations responsible tended to be purged in the first few generations after colonization, but its effects increased again as populations grow older as a result of immigration. Our results point to a need for estimates of genetic diversity, genetic load, within‐deme inbreeding depression and heterosis in demes of different age classes separately.     

Patterns of inbreeding depression and architecture of the load in subdivided populations

Inbreeding depression is a general phenomenon that is due mainly to recessive deleterious mutations, the so-called mutation load. It has been much studied theoretically. However, until very recently, population structure has not been taken into account, even though it can be an important factor in the evolution of populations. Population subdivision modifies the dynamics of deleterious mutations because the outcome of selection depends on processes both within populations (selection and drift) and between populations (migration). Here, we present a general model that permits us to gain insight into patterns of inbreeding depression, heterosis, and the load in subdivided populations. We show that they can be interpreted with reference to single-population theory, using an appropriate local effective population size that integrates the effects of drift, selection, and migration. We term this the "effective population size of selection" (NS(e)). For the infinite island model, for example, it is equal to NS(e) = N1 + m/hs, where N is the local population size, m the migration rate, and h and s the dominance and selection coefficients of deleterious mutation. Our results have implications for the estimation and interpretation of inbreeding depression in subdivided populations, especially regarding conservation issues. We also discuss the possible effects of migration and subdivision on the evolution of mating systems.     

Heterosis and outbreeding depression in crosses between natural populations of Arabidopsis thaliana

Understanding the causes and architecture of genetic differentiation between natural populations is of central importance in evolutionary biology. Crosses between natural populations can result in heterosis if recessive or nearly recessive deleterious mutations have become fixed within populations because of genetic drift. Divergence between populations can also result in outbreeding depression because of genetic incompatibilities. The net fitness consequences of between-population crosses will be a balance between heterosis and outbreeding depression. We estimated the magnitude of heterosis and outbreeding depression in the highly selfing model plant Arabidopsis thaliana, by crossing replicate line pairs from two sets of natural populations (C↔R, B↔S) separated by similar geographic distances (Italy↔Sweden). We examined the contribution of different modes of gene action to overall differences in estimates of lifetime fitness and fitness components using joint scaling tests with parental, reciprocal F₁ and F₂, and backcross lines. One of these population pairs (C↔R) was previously demonstrated to be locally adapted, but locally maladaptive quantitative trait loci were also found, suggesting a role for genetic drift in shaping adaptive variation. We found markedly different genetic architectures for fitness and fitness components in the two sets of populations. In one (C↔R), there were consistently positive effects of dominance, indicating the masking of recessive or nearly recessive deleterious mutations that had become fixed by genetic drift. The other set (B↔S) exhibited outbreeding depression because of negative dominance effects. Additional studies are needed to explore the molecular genetic basis of heterosis and outbreeding depression, and how their magnitudes vary across environments.     

Heterosis for viability,fecundity, and male fertility in Drosophila melanogaster: comparison of mutational and standing variation.

If genetic variation for fitness traits in natural populations ("standing" variation) is maintained by recurrent mutation, then quantitative-genetic properties of standing variation should resemble those of newly arisen mutations. One well-known property of standing variation for fitness traits is inbreeding depression, with its converse of heterosis or hybrid vigor. We measured heterosis for three fitness traits, pre-adult viability, female fecundity, and male fertility, among a set of inbred Drosophilia melanogaster lines recently derived from the wild, and also among a set of lines that had been allowed to accumulate spontaneous mutations for over 200 generations. The inbred lines but not the mutation-accumulation (MA) lines showed heterosis for pre-adult viability. Both sets of lines showed heterosis for female fecundity, but heterosis for male fertility was weak or absent. Crosses among a subset of the MA lines showed that they were strongly differentiated for male fertility, with the differences inherited in autosomal fashion; the absence of heterosis for male fertility among the MA lines was therefore not caused by an absence of mutations affecting this trait. Crosses among the inbred lines also gave some, albeit equivocal, evidence for male fertility variation. The contrast between the results for female fecundity and those for male fertility suggests that mutations affecting different fitness traits may differ in their average dominance properties, and that such differences may be reflected in properties of standing variation. The strong differentiation among the MA lines in male fertility further suggests that mutations affecting this trait occur at a high rate.     

Inbreeding reveals stronger net selection on Drosophila melanogaster males: implications for mutation load and the fitness of sexual females

Stronger selection on males has the potential to lower the deleterious mutation load of females, reducing the cost of sex. However, few studies have directly quantified the strength of selection for both sexes. As the magnitude of inbreeding depression (ID) is related to the strength of selection, we measured the cost of inbreeding for both males and females in a laboratory population of Drosophila melanogaster. Using a novel technique for inbreeding, we found significant ID for both juvenile viability and adult fitness in both sexes. The genetic variation responsible for this depression in fitness appeared to be recessive for adult fitness (h=0.11) and partially additive for juvenile viability (h=0.29). ID was identical across the sexes in terms of juvenile viability but was significantly more deleterious for males than females as adults, even though female X-chromosome homogamety should predispose them to a higher inbreeding load. We estimated the strength of selection on adult males to be 1.24 greater than on adult females, and this appears to be a consequence of selection arising from competition for mates. Combined with the generally positive intersexual genetic correlation for inbred lines, our results suggest that the mutation load of sexual females could be meaningfully reduced by stronger selection acting on males.     

Dynamics of inbreeding depression due to deleterious mutations in small populations: mutation parameters and inbreeding rate

A multilocus stochastic model is developed to simulate the dynamics of mutational load in small populations of various sizes. Old mutations sampled from a large ancestral population at mutation-selection balance and new mutations arising each generation are considered jointly, using biologically plausible lethal and deleterious mutation parameters. The results show that inbreeding depression and the number of lethal equivalents due to partially recessive mutations can be partly purged from the population by inbreeding, and that this purging mainly involves lethals or detrimentals of large effect. However, fitness decreases continuously with inbreeding, due to increased fixation and homozygosity of mildly deleterious mutants, resulting in extinctions of very small populations with low reproductive rates. No optimum inbreeding rate or population size exists for purging with respect to fitness (viability) changes, but there is an optimum inbreeding rate at a given final level of inbreeding for reducing inbreeding depression or the number of lethal equivalents. The interaction between selection against partially recessive mutations and genetic drift in small populations also influences the rate of decay of neutral variation. Weak selection against mutants relative to genetic drift results in apparent overdominance and thus an increase in effective size (Ne) at neutral loci, and strong selection relative to drift leads to a decrease in Ne due to the increased variance in family size. The simulation results and their implications are discussed in the context of biological conservation and tests for purging.     

Inbreeding,inbreeding depression and extinction

Inbreeding is unavoidable in small, isolated populations and can cause substantial fitness reductions compared to outbred populations. This loss of fitness has been predicted to elevate extinction risk giving it substantial conservation significance. Inbreeding may result in reduced fitness for two reasons: an increased expression of deleterious recessive alleles (partial dominance hypothesis) or the loss of favourable heterozygote combinations (overdominance hypothesis). Because both these sources of inbreeding depression are dependent upon dominance variance, inbreeding depression is predicted to be greater in life history traits than in morphological traits. In this study we used replicate inbred and control lines of Drosophila simulans to address three questions:1) is inbreeding depression greater in life history than morphological traits? 2) which of the two hypotheses is the major underlying cause of inbreeding depression? 3) does inbreeding elevate population extinction risk? We found that inbreeding depression was significantly greater in life history traits compared to morphological traits, but were unable to find unequivocal support for either the overdominance or partial dominance hypotheses as the genetic basis of inbreeding depression. As predicted, inbred lines had a significantly greater extinction risk.     

Inbreeding depression: tests of the overdominance and partial dominance hypotheses

The two principal theories of the causal mechanism for inbreeding depression are the partial dominance hypothesis and the overdominance hypothesis. According to the first hypothesis, inbreeding increases the frequency of homozygous combinations of deleterious recessive alleles thereby decreasing fitness, whereas the overdominance hypothesis posits that inbreeding increases homozygosity and thus reduces the frequency of the superior heterozygotes. These two hypotheses make different predictions on the effect of crossing inbred lines: the overdominance hypothesis predicts that trait means will be restored to the outbred means, whereas the partial dominance hypothesis predicts that trait means will exceed those of the outbred population. I tested these predictions using seven inbred lines of the sand cricket, Gryllus firmus. Fourteen generations of brother-sister mating resulted in an inbreeding depression of 20-34% in four traits: nymphal weights at ages 14 days, 21 days, 28 days, and early fecundity. An incomplete diallel cross of these lines showed genetic variation among lines and an increase in all trait means above the outbred means, with three being significantly higher. These results provide support for the partial dominance hypothesis and are inconsistent with the overdominance hypothesis.     

Inbreeding depression in insular and central populations of Peromyscus mice

We tested the hypothesis that small, isolated populations would show less depression in fitness when inbred than would large, central populations. Laboratory stocks of Peromyscus leucopus and P. polionotus were established from insular, peninsular, and central populations. The isolated populations had one-third to one-half the genic diversity of central populations. Responses to inbreeding were highly varied: some populations had smaller litters, others experienced higher mortality, some showed slower growth rates, and one displayed no measurable effects when inbred. These results suggest that inbreeding depression is controlled by a small number of genes and that the size of the genetic load depends on which alleles are present in the founders of a population. The severity of fitness depression in inbred litters did not correlate with initial genic diversity of the stocks nor, therefore, with the size of the wild populations. Fitness measures appeared linearly related to the inbreeding coefficient of the liters, with no diminution of deleterious effects through subsequent generations of inbreeding. Thus overdominance of fitness traits probably contributed as much to the genetic load as did deleterious recessive alleles. The inbreeding level of the dam negatively affected the size, growth, and survival of litters only in genetically diverse populations, indicating that the load of recessive alleles negatively impacting maternal care may have been reduced by selection in the more peripheral populations during past bottlenecks.