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Mean d(2) and divergence time: transformations and standardizations.

The fitness consequences of inbreeding and outbreeding have intrigued biologists for a long time. Recently a measure of relatedness of parental haplotypes has been proposed called mean d(2). This measure is based on a stepwise mutational process and therefore is tailored to microsatellite genetic markers. Theoretical work suggests that mean d(2) typically is less suited for measuring fitness consequences due to close inbreeding rather than heterozygosity. However, mean d(2) may be more appropriate than heterozygosity for measuring divergence times over longer time scales and thus for detecting outbreeding depression. Here, simulations are used to (1). identify appropriate standardization coefficients and transformations for mean d(2), and (2). evaluate mean d(2) as a measure of divergence time of parental lineages over time scales up to 10000 generations. Results show that mean d(2) is a linear predictor of divergence time. The coefficient of variation of mean d(2) approaches a constant value with increasing divergence time and therefore logarithm transformation is appropriate to restore homoscedasticity. When mutation rates and sizes are known for each locus they can be incorporated into a standardization coefficient to increase the precision of mean d(2). As few as 10 loci can explain more than 70% of the variation in divergence time between lineages. While heterozygosity outperforms mean d(2) at detecting differences in divergence time over relative short time periods ( or=1000 generations). However, gene flow of as little as 1% per generation can significantly reduce the ability of either mean d(2) or heterozygosity to estimate divergence time.

Computer Simulation↗

Breed structure of Senepol cattle.

Data were collected by the Virgin Islands Beef Cattle Improvement Program and the Virgin Islands Agricultural Experiment Station staff to establish the breed structure of the Senepol cattle. Data for the analysis were limited to the two Virgin Islands Senepol breeders with the most complete and largest set of records, representing approximately 65% of the entire Senepol population. Inbreeding (F) and coancestry relationship coefficients (rAB) and the theoretical inbreeding (FT) were determined from each data set and for the combined data from both farms, for each year, ranging from 1947 to 1984 for Annaly Farms, and from 1967 to 1984 for Castle Nugent Farm. The data sets for both farms were examined for the possibility of separation into families. Actual F within the Senepol population was relatively low, averaging less than 1.00%. Some separation into families occurred within Annaly Farms' cattle. The F and FT decreased (1.6 to 0.7% and 1.0 to 0.2%, respectively) as population numbers increased. The low F was accomplished through the breeding programs and exchanges of animals between farms on the island.

Animals↗

Development, genotype and phenotype of a new colony of the Sabra hypertension prone (SBH/y) and resistant (SBN/y) rat model of slat sensitivity and resistance.

OBJECTIVES: Variations in the blood pressure response to salt-loading, the lack of quality control measures, and the need to prepare the strains for genetic studies led to renewed secondary inbreeding of the original colony of Sabra hypertension prone (SBH) and resistant (SBN) rats in order to regain genotypic and phenotypic homogeneity of the substrains. METHODS: Animals from the original breeding colony were selectively inbred for basal normotension and for susceptibility or resistance to the development of hypertension following salt-loading with deoxycorticosterone acetate (DOCA)-salt. Efficacy of inbreeding was tested by genome screening with 416 microsatellite primer sets. Phenotyping was based on measurements of systolic blood pressure by the tail-cuff methodology in awake, undisturbed animals maintained on standard diet and after salt-loading with DOCA-salt. Telemetric measurements of blood pressure were performed in a small number of animals to validate tail-cuff measurements. RESULTS: Animals from the new colony were designated SBH/y and SBN/y to differentiate from the original colony. Fourteen generations have been inbred over the past 4 years. Of the 402 microsatellites that amplified, 183 (45.5%) were polymorphic between the two substrains, and not a single locus was found to be heterozygous in either substrain. Phenotypic characteristics are provided for SBH/ y and SBN/y rats with respect to tail-cuff systolic blood pressure. The values obtained, which were validated by telemetry, demonstrate classical features of salt sensitivity or resistance, respectively. CONCLUSIONS: The genetic homogeneity found in SBH/y and SBN/y, the phenotype demonstrating salt-sensitivity or salt-resistance in terms of development of hypertension, and the relatively high frequency of informative genetic markers identify this Sabra rat model as highly suited for studies concerning the molecular genetics of gene-environment interactions affecting blood pressure regulation.

Animals↗

Extrapair mating between relatives in the barn swallow: a role for kin selection?

Why do females of many species mate with more than one male? One of the main hypotheses suggests that female promiscuity is an insurance mechanism against the potential detrimental effects of inbreeding. Accordingly, females should preferably mate with less related males in multiple or extrapair mating. Here we analyse paternity, relatedness among mating partners, and relatedness between parents and offspring, in the socially monogamous North American barn swallow (Hirundo rustica erythrogaster). In contrast to the inbreeding avoidance hypothesis, we found that extrapair mating partners were more related than expected by random choice, and tended to be more related than social partners. Furthermore, extrapair mating resulted in genetic parents being more related to their extrapair young than to their withinpair young. We propose a new hypothesis for extrapair mating based on kin selection theory as a possible explanation to these findings.

Animals↗

The influence of parental relatedness on reproductive success.

The relationship between fitness and parental similarity has been dominated by studies of how inbreeding depression lowers fecundity in incestuous matings. A widespread implicit assumption is that adult fitness (reproduction) of individuals born to parents who are not unusually closely related is more or less equal. Examination of three long-lived vertebrates, the long-finned pilot whale, the grey seal and the wandering albatross reveals significant negative relationships between parental similarity and genetic estimates of reproductive success. This effect could, in principle, be driven by a small number of low quality, inbred individuals. However, when the data are partitioned into individuals with above average and below average parental similarity, we find no evidence that the slopes differ, suggesting that the effect is more or less similar across the full range of parental similarity values. Our results thus uncover a selective pressure that favours not only inbreeding avoidance, but also the selection of maximally dissimilar mates.

Animals↗

Two classes of deleterious recessive alleles in a natural population of zebrafish, Danio rerio.

Natural populations carry deleterious recessive alleles which cause inbreeding depression. We compared mortality and growth of inbred and outbred zebrafish, Danio rerio, between 6 and 48 days of age. Grandparents of the studied fish were caught in the wild. Inbred fish were generated by brother-sister mating. Mortality was 9% in outbred fish, and 42% in inbred fish, which implies at least 3.6 lethal equivalents of deleterious recessive alleles per zygote. There was no significant inbreeding depression in the growth, perhaps because the surviving inbred fish lived under less crowded conditions. In contrast to alleles that cause embryonic and early larval mortality in the same population, alleles responsible for late larval and early juvenile mortality did not result in any gross morphological abnormalities. Thus, deleterious recessive alleles that segregate in a wild zebrafish population belong to two sharply distinct classes: early-acting, morphologically overt, unconditional lethals; and later-acting, morphologically cryptic, and presumably milder alleles.

Alleles↗

Host cell preference and variable transmission strategies in malaria parasites.

Malaria and other haemosporin parasites must undergo a round of sexual reproduction in their insect vector in order to produce stages that can be transmitted to vertebrate hosts. Consequently, it is crucial that parasites produce the sex ratio (proportion of male sexual stages) that will maximize the number of fertilization and thus, transmission to new vertebrate hosts. There is some evidence to show that, consistent with evolutionary theory, the sex ratios of malaria parasites are negatively correlated to their inbreeding rate. However, recent theory has shown that when fertilization success is compromised, parasites should respond by increasing their investment in sexual stages or by producing a less female biased ration than predicted by their inbreeding rate alone. Here, we show that two species of rodent malaria, Plasmodium chabaudi and Plasmodium vinckei petteri, adopt different strategies in response to host anaemia, a factor though to compromise transmission success: P. chabaudi increases investment in sexual stages, whereas P. vinckei produces a less female biased sex ratio. We suggest that these different transmission strategies may be due to marked differences in host cell preference.

Anemia↗

Genomic compatibility occurs over a wide range of parental genetic similarity in an outcrossing plant.

The theory of inbreeding and outbreeding suggests that there is a hump-shaped relationship between the genetic similarity of sexually reproducing parents and the performance of their offspring. Inbreeding depression occurs when genetic similarity is high, whereas hybrid breakdown is expected when genetic similarity is low. Between these extremes, the effect of genetic similarity on fitness is unclear. We studied the shape of this relationship by crossing 65 target genotypes of the clonal, self-incompatible Ranunculus reptans with partner genotypes spanning a broad scale of genetic similarity, ranging from crosses within populations to between-population crosses and hybridisation with a closely related species. Offspring were raised in outdoor tubs. Results revealed a quadratic relationship between parental genetic distance and offspring performance, with the clonal component of fitness more strongly hump-shaped than the sexual component. Optimal genetic similarity encompassed a broad range of within-population and between-population crosses. This pattern of genomic compatibility has important implications for the evolution of mating systems and mate choice.

Analysis of Variance↗

Negative environmental perturbations may improve species persistence.

Among the factors proximally involved in the extinction of small isolated populations, genetic deterioration and temporal variation in environmental quality have been the subjects of intensive research in ecological and evolutionary sciences. However, previous theoretical studies and population viability assessments generally assumed a strict dichotomy between these two types of threat. Yet a number of empirical studies have recently suggested that the effects of genetic deterioration and environmental variation should not be considered independently, by demonstrating that the main effect of inbreeding depression lies with its tendency to exacerbate the deleterious consequences of environmental stress. Capitalizing on these results, I developed a stochastic model to examine the impact of random environmental perturbations on the persistence time of small isolated populations subject to inbreeding depression and mutation accumulation. The model assumes that spontaneous deleterious mutations have more severe effects when perturbations occur, which results in more efficient purging of the mutation load. Under this assumption, I find that negative perturbations may paradoxically improve middle- and long-term species persistence for realistic frequency of occurrence and severity distribution.

Animals↗

Genotypic and phenotypic consequences of domestication in dogs.

Runs of homozygosity (ROH) are genomic regions that arise when two copies of identical haplotypes are inherited from a shared common ancestor. In this study, we leverage ROH to identify associations between genetic diversity and non-disease phenotypes in Canis lupus familiaris (dogs). We find significant association between the ROH inbreeding coefficient (FROH) and several phenotypic traits. These traits include height, weight, lifespan, muscled, white coloring of the head and chest, furnishings, and fur length. After correcting for population structure, we identified more than 45 genes across the examined quantitative traits that exceed the threshold for suggestive significance. We observe distinct distributions of inbreeding and elevated levels of long ROH in modern breed dogs compared to more ancient breeds, which aligns with breeding practices during Victorian era breed establishment. Our results highlight the impact of non-additive variation and of polygenicity on complex quantitative phenotypes in dogs due to domestication and the breed formation bottleneck.

GWAS↗

Population dynamics with and without selection.

A model describing population dynamics is presented. We study the effect of selection pressure and inbreeding on the time evolution of the population and the chances of survival. We find that the selection is in general beneficial, enabling survival of a population whose size is declining. Inbreeding reduces the survival chances since it leads to clustering of individuals. We have also found, in agreement with biological data, that there is a threshold value of the initial size of the population, as well as of the habitat, below which the population will almost certainly become extinct. We present analytical and computer simulation approaches.

Biological Evolution↗

Population size and fragmentation thresholds for the maintenance of genetic diversity in the herbaceous endemic Scutellaria montana (Lamiaceae).

Abstract.-The level and distribution of genetic variation is thought to be affected primarily by the size of individual populations and by gene flow among populations. Although the effects of population size have frequently been examined, the contributions of regional gene flow to levels of genetic variation are less well known. Here I examine the effects of population size and the number of neighboring populations (metapopulation density) on the distribution and maintenance of genetic diversity in an endemic herbaceous perennial. Reductions in the proportion of polymorphic loci and the effective number of alleles per locus were apparent for many populations with a census size of less than 100 individuals, but no effects of population size on levels of inbreeding were detected. I assess the effects of regional population density on levels of diversity and inbreeding using stepwise regression analysis of metapopulation diameter (i.e., the size of a circle within which population density is estimated). This procedure provides a spatially explicit evaluation of the effects of metapopulation size on population genetic parameters and indicates the critical number of neighboring populations (fragmentation threshold) for the regional maintenance of genetic diversity. Stepwise regression analyses revealed fragmentation thresholds at two levels; at a scale of 2 km, where small metapopulations resulted in greater levels of selfing or sibling mating, and at a scale of 8 km, where metapopulation size was positively associated with higher levels of genetic diversity. I hypothesize that the smaller fragmentation threshold may reflect higher levels of selfing in isolated populations because of the absence of pollinators. The larger threshold probably indicates the maximum distance over which pollen dispersal rates are high enough to counteract genetic drift. This study demonstrates that the regional distribution of populations can be an important factor for the long-term maintenance of genetic variation.

Alleles↗

Sperm competitive ability and genetic relatedness in Drosophila melanogaster: similarity breeds contempt.

Offspring of close relatives often suffer severe fitness consequences. Previous studies have demonstrated that females, when given a choice, will choose to avoid mating with closely related males. But where opportunities for mate choice are limited or kin recognition is absent, precopulatory mechanisms may not work. In this case, either sex could reduce the risks of inbreeding through mechanisms that occur during or after copulation. During mating, males or females could commit fewer gametes when mating with a close relative. After mating, females could offset the effects of mating with a closely related male through cryptic choice. Few prior studies of sperm competition have examined the effect of genetic similarity, however, and what studies do exist have yielded equivocal results. In an effort to resolve this issue, we measured the outcome of sperm competition when female Drosophila melanogaster were mated to males of four different degrees of genetic relatedness and then to a standardized competitor. We provide the strongest evidence to date that sperm competitive ability is negatively correlated with relatedness, even after controlling for inbreeding depression.

Animals↗

Mate choice, genetic incompatibility, and outbreeding in the ornate dragon lizard, Ctenophorus ornatus.

There has been recent interest in the role genetic incompatibility may play in mate or sperm choice. One source of incompatibility may be too similar or disparate genomes. An isolated population of the ornate dragon lizard, Ctenophorus ornatus, was followed over a breeding season and parentage assigned to the offspring using microsatellites. It was found that the adults in the population had an eight per cent chance of mating with a relative. I examined whether C. ornatus mate (or fertilize their eggs) with respect to genetic similarity. There was no difference in a female's relatedness to the male in whose territory she resided and her average relatedness to all other males. Neither was there a difference in the relatedness of the male that sired a female's offspring and the female's average relatedness to all other males. There was no evidence of a cost to mating with a more genetically similar mate, because offspring survival was not influenced by degree of inbreeding or outbreeding. However, females that were more outbred had fewer offspring survive. In this small population there are two possible explanations for the decreased fitness associated with outbreeding. First, the species may have an evolutionary history of inbreeding and thus may be susceptible to outbreeding depression. Second. as fitter individuals produce more offspring, these offspring have an increased probability of breeding with relatives, leading to an indirect relationship between fitness and outbreeding.

Animals↗

Flower and cotyledon asymmetry in Brassica cretica: genetic variation and relationships with fitness.

Plants of the partially self-incompatible perennial herb Brassica cretica, derived from controlled cross- and self-pollinations within each of seven populations, were raised under uniform conditions and scored for two measures of developmental stability, flower asymmetry (quantified as the difference in length and width between opposite petals) and cotyledon asymmetry (quantified as the difference in the area of the two lobes of each cotyledon). The primary goals were to assess the level of heritable variation in asymmetry, the effect of selfing on mean asymmetry, and the relationship between asymmetry and components of fitness. A paternal half-sibling analysis of data on flower asymmetry failed to detect significant levels of genetic variation at the within-population level, whereas the between-population component reached significance for all measures of asymmetry. Analysis of family-structured data from another crossing experiment revealed significant between-population variation in cotyledon asymmetry and a tendency for inbred progeny to produce more asymmetric cotyledons than outbred progeny. However, the response to inbreeding was weak and differed in magnitude between populations. Judging from the ranking of populations, we found no support for the hypothesis that the mean expression of developmental stability is controlled by genomewide characteristics such as the level of inbreeding. Correlations between measures of asymmetry and fitness were too low to be declared statistically or biologically significant. The present study provides little evidence that flower and cotyledon asymmetry serve as more appropriate predictors of genetic health than conventional (direct) measures of fitness.

Analysis of Variance↗

How a hybrid zone is maintained: behavioral mechanisms of interbreeding between California and Gambel's quail (Callipepla californica and C. gambelii).

Hybridizing California and Gambel's Quail (Callipepla californica and C. gambelii) are unlike many hybridizing avian species in that pairing primarily occurs within a flock, or covey, that is composed of several families. Coveys in the area of sympatry contain mostly hybrid individuals, relative to parental types. I tested whether individuals perceive covey mates as a single species and whether pairing within the covey causes inbreeding and a loss of reproductive success. Individuals discriminated between the parental species in captivity, but actual pairing in the wild was random with respect to species. Contrary to expectation, coveys were not more inbred than the local population. Results suggest that potential costs of inbreeding may be avoided through sex-biased dispersal and nonrandom pairing. Furthermore, breeding occurred earlier and with greater success in pairs formed within the resident covey, rather than outside it. These findings suggest that fitness benefits gained from pairing early within a mixed-species covey promote interspecific pairing. This study provides evidence that mating behaviors specific to local conditions maintain hybrid zones when genetic costs to interbreeding are small.

Animals↗

The additive genetic variance after bottlenecks is affected by the number of loci involved in epistatic interactions.

We investigated the role of the number of loci coding for a neutral trait on the release of additive variance for this trait after population bottlenecks. Different bottleneck sizes and durations were tested for various matrices of genotypic values, with initial conditions covering the allele frequency space. We used three different types of matrices. First, we extended Cheverud and Routman's model by defining matrices of "pure" epistasis for three and four independent loci; second, we used genotypic values drawn randomly from uniform, normal, and exponential distributions; and third we used two models of simple metabolic pathways leading to physiological epistasis. For all these matrices of genotypic values except the dominant metabolic pathway, we find that, as the number of loci increases from two to three and four, an increase in the release of additive variance is occurring. The amount of additive variance released for a given set of genotypic values is a function of the inbreeding coefficient, independently of the size and duration of the bottleneck. The level of inbreeding necessary to achieve maximum release in additive variance increases with the number of loci. We find that additive-by-additive epistasis is the type of epistasis most easily converted into additive variance. For a wide range of models, our results show that epistasis, rather than dominance, plays a significant role in the increase of additive variance following bottlenecks.

Epistasis, Genetic↗

Does linkage disequilibrium generate heterozygosity-fitness correlations in great reed warblers?

Heterozygosity-fitness correlations (HFCs) at noncoding genetic markers are commonly assumed to reflect fitness effects of heterozygosity at genomewide distributed genes in partially inbred populations. However, in populations with much linkage disequilibrium (LD), HFCs may arise also as a consequence of selection on fitness loci in the local chromosomal vicinity of the markers. Recent data suggest that relatively high levels of LD may prevail in many ecological situations. Consequently, LD may be an important factor, together with partial inbreeding, in causing HFCs in natural populations. In the present study, we evaluate whether LD can generate HFCs in a small and newly founded population of great reed warblers (Acrocephalus arundinaceus). For this purpose dyads of full siblings of which only one individual survived to adult age (i.e., returned to breed at the study area) were scored at 19 microsatellite loci, and at a gene region of hypothesized importance for survival, the major histocompatibility complex (MHC). By examining siblings, we controlled for variation in the inbreeding coefficient and thus excluded genome-wide fitness effects in our analyses. We found that recruited individuals had significantly higher multilocus heterozygosity (MLH), and mean d2 (a microsatellite-specific variable), than their nonrecruited siblings. There was a tendency for the survivors to have a more diverse MHC than the nonsurvivors. Single-locus analyses showed that the strength of the genotype-survival association was especially pronounced at four microsatellite loci. By using genotype data from the entire breeding population, we detected significant LD between five of 162 pairs of microsatellite loci after accounting for multiple tests. Our present finding of a significant within-family multilocus heterozygosity-survival association in a nonequilibrium population supports the view that LD generates HFCs in natural populations.

Animals↗