Evidence For Heterozygote Advantage Research Articles

Contemporary evolution of the innate immune receptor gene TLR3 in an isolated vertebrate population.

Understanding where genetic variation exists, and how it influences fitness within populations is important from an evolutionary and conservation perspective. Signatures of past selection suggest that pathogen-mediated balancing selection is a key driver of immunogenetic variation, but studies tracking contemporary evolution are needed to help resolve the evolutionary forces and mechanism at play. Previous work in a bottlenecked population of Seychelles warblers (Acrocephalus sechellensis) show that functional variation has been maintained at the viral-sensing Toll-like receptor 3 (TLR3) gene, including one nonsynonymous SNP, resulting in two alleles. Here, we characterise evolution at this TLR3 locus over a 25-year period within the original remnant population of the Seychelles warbler, and in four other derived, populations. Results show a significant and consistent temporal decline in the frequency of the TLR3C allele in the original population, and that similar declines in the TLR3C allele frequency occurred in all the derived populations. Individuals (of both sexes) with the TLR3CC genotype had lower survival, and males - but not females - that carry the TLR3C allele had significantly lower lifetime reproductive success than those with only the TLR3A allele. These results indicate that positive selection on the TLR3A allele, caused by an as yet unknown agent, is driving TLR3 evolution in the Seychelles warbler. No evidence of heterozygote advantage was detected. However, whether the positive selection observed is part of a longer-term pattern of balancing selection (through fluctuating selection or rare-allele advantage) cannot be resolved without tracking the TLR3C allele over an extended time period.

A single pleiotropic locus influences the rate of hybridization between two sibling species of Lygaeus bugs.

The evolution of reproductive isolation lies at the heart of understanding the process of speciation. Of particular interest is the relationship between pre‐ and postzygotic reproductive isolation, and the genetic architecture of traits that contribute to one or both forms of reproductive isolation. The sibling species of seed bug Lygaeus equestris and L. simulans show a classic pattern of asymmetric prezygotic reproductive isolation, with female L. equestris hybridizing with male L. simulans, but with no hybridization in the reciprocal direction. We have recently described a mutant pale color form of L. simulans, that inherits as a single Mendelian locus and is pleiotropic for a number of other life history and behavioral traits. Here, we tested whether this locus also influences pre‐ and postzygotic reproductive isolation. Two sets of experimental crosses revealed that behavioral isolation varied with mutant versus wild‐type phenotype for male L. simulans, with the pale form less successful at mating with female L. equestris. In terms of trying to assess postzygotic isolation, levels of hybrid offspring production were uniformly low across the experiments. However, we did obtain, for the first time, hybrid offspring from a pairing between a female L. simulans and a male L. equestris. In this instance, the female was of the pale mutant genotype. Together with evidence for heterozygote advantage in terms of nymph survival, we consider our results in terms of possible mechanisms of reproductive isolation between this species pair, the role of the pale mutation, and the possible genetic architectures underlying the mutation, from a single gene to a supergene.

Hardy-Weinberg Equilibrium in the Large Scale Genomic Sequencing Era.

Hardy-Weinberg Equilibrium (HWE) is used to estimate the number of homozygous and heterozygous variant carriers based on its allele frequency in populations that are not evolving. Deviations from HWE in large population databases have been used to detect genotyping errors, which can result in extreme heterozygote excess (HetExc). However, HetExc might also be a sign of natural selection since recessive disease causing variants should occur less frequently in a homozygous state in the population, but may reach high allele frequency in a heterozygous state, especially if they are advantageous. We developed a filtering strategy to detect these variants and applied it on genome data from 137,842 individuals. The main limitations of this approach were quality of genotype calls and insufficient population sizes, whereas population structure and inbreeding can reduce sensitivity, but not precision, in certain populations. Nevertheless, we identified 161 HetExc variants in 149 genes, most of which were specific to African/African American populations (∼79.5%). Although the majority of them were not associated with known diseases, or were classified as clinically “benign,” they were enriched in genes associated with autosomal recessive diseases. The resulting dataset also contained two known recessive disease causing variants with evidence of heterozygote advantage in the sickle-cell anemia (HBB) and cystic fibrosis (CFTR). Finally, we provide supporting in silico evidence of a novel heterozygote advantageous variant in the chromodomain helicase DNA binding protein 6 gene (CHD6; involved in influenza virus replication). We anticipate that our approach will aid the detection of rare recessive disease causing variants in the future.

Pathogen burden, co-infection and major histocompatibility complex variability in the European badger (Meles meles).

Pathogen-mediated selection is thought to maintain the extreme diversity in the major histocompatibility complex (MHC) genes, operating through the heterozygote advantage, rare-allele advantage and fluctuating selection mechanisms. Heterozygote advantage (i.e. recognizing and binding a wider range of antigens than homozygotes) is expected to be more detectable when multiple pathogens are considered simultaneously. Here, we test whether MHC diversity in a wild population of European badgers (Meles meles) is driven by pathogen-mediated selection. We examined individual prevalence (infected or not), infection intensity and co-infection of 13 pathogens from a range of taxa and examined their relationships with MHC class I and class II variability. This population has a variable, but relatively low, number of MHC alleles and is infected by a variety of naturally occurring pathogens, making it very suitable for the investigation of MHC-pathogen relationships. We found associations between pathogen infections and specific MHC haplotypes and alleles. Co-infection status was not correlated with MHC heterozygosity, but there was evidence of heterozygote advantage against individual pathogen infections. This suggests that rare-allele advantages and/or fluctuating selection, and heterozygote advantage are probably the selective forces shaping MHC diversity in this species. We show stronger evidence for MHC associations with infection intensity than for prevalence and conclude that examining both pathogen prevalence and infection intensity is important. Moreover, examination of a large number and diversity of pathogens, and both MHC class I and II genes (which have different functions), provide an improved understanding of the mechanisms driving MHC diversity.

Antagonistic experimental coevolution with a parasite increases host recombination frequency

BackgroundOne of the big remaining challenges in evolutionary biology is to understand the evolution and maintenance of meiotic recombination. As recombination breaks down successful genotypes, it should be selected for only under very limited conditions. Yet, recombination is very common and phylogenetically widespread. The Red Queen Hypothesis is one of the most prominent hypotheses for the adaptive value of recombination and sexual reproduction. The Red Queen Hypothesis predicts an advantage of recombination for hosts that are coevolving with their parasites. We tested predictions of the hypothesis with experimental coevolution using the red flour beetle, Tribolium castaneum, and its microsporidian parasite, Nosema whitei.ResultsBy measuring recombination directly in the individuals under selection, we found that recombination in the host population was increased after 11 generations of coevolution. Detailed insights into genotypic and phenotypic changes occurring during the coevolution experiment furthermore helped us to reconstruct the coevolutionary dynamics that were associated with this increase in recombination frequency. As coevolved lines maintained higher genetic diversity than control lines, and because there was no evidence for heterozygote advantage or for a plastic response of recombination to infection, the observed increase in recombination most likely represented an adaptive host response under Red Queen dynamics.ConclusionsThis study provides direct, experimental evidence for an increase in recombination frequency under host-parasite coevolution in an obligatory outcrossing species. Combined with earlier results, the Red Queen process is the most likely explanation for this observation.

Common CFTR gene variants influence body composition and survival in rural Ghana

Various studies in mice have found support for the hypothesis that heterozygous carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations have an increased resistance to fatal infection compared to both homozygous mutation carriers and non-carriers, while in humans such evidence is scarce. In this study, we assessed the CFTR heterozygotes survival advantage hypothesis in a contemporary rural population that lives under adverse environmental conditions in the Upper-East region of Ghana. We genotyped 30 SNPs throughout the CFTR gene in 4,230 participants and tested their influence on survival and on body composition in the population at large. With a sliding-window haplotype analysis, we identified a set of six common haplotypes that influenced survival probabilities (global p = 6.00 × 10−05). Individual haplotype analyses revealed two haplotypes of specific interest. One of these haplotypes was enriched (p = 0.003), whereas the other was depleted (p = 0.041) among people of old age (≥65 years) compared to young study participants (≤5 years). In addition, children (n = 474) carrying the latter haplotype had lower body weight (p trend = 0.020) and height (p trend = 0.010) compared to non-carriers. For all these analyses, similar associations for heterozygous and homozygous CFTR haplotype carriers were observed, revealing an additive effect of haplotype alleles. In conclusion, we identified common haplotypes in the CFTR gene that influence survival and body composition in the population at large with no evidence for heterozygote advantage.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-009-0762-2) contains supplementary material, which is available to authorized users.

Pathogens as potential selective agents in the wild

Pathogens are considered a serious threat to which wild populations must adapt, most particularly under conditions of rapid environmental change. One way host adaptation has been studied is through genetic population structure at the major histocompatibility complex (MHC), a complex of adaptive genes involved in pathogen resistance in vertebrates. However, while associations between specific pathogens and MHC alleles or diversity have been documented from laboratory studies, the interaction between hosts and pathogens in the wild is more complex. As such, identifying selective agents and understanding underlying co-evolutionary mechanisms remains a major challenge. In this issue of Molecular Ecology, Evans & Neff (2009) characterized spatial and temporal variation in the bacterial parasite community infecting Chinook salmon (Oncorhynchus tshawytscha) fry from five populations in British Columbia, Canada. They used a 16S rDNA sequencing-based approach to examine the prevalence of bacterial infection in kidney and looked for associations with MHC class I and II genetic variability. The authors found a high diversity of bacteria infecting fry, albeit at low prevalence. It was reasoned that spatial variability in infection rate and bacterial community phylogenetic similarity found across populations may represent differential pathogen-mediated selection pressures. The study revealed some evidence of heterozygote advantage at MHC class II, but not class I, and preliminary associations between specific MHC alleles and bacterial infections were uncovered. This research adds an interesting perspective to the debate on host-pathogen co-evolutionary mechanisms and emphasizes the importance of considering the complexity of pathogen communities in studies of host local adaptation.

Differences in Fitness Components among Alcohol Dehydrogenase Genotypes of the Olive Fruit Fly (Diptera: Tephritidae) under Artificial Rearing

Previous studies have shown that natural populations of the olive fruit fly, Bactrocera oleae (Gmelin), segregate for 3 electrophoretically distinguishable alleles (allozymes S, F, and I) at the alcohol dehydrogenase (ADH) locus. Allele I is rare, but in colonies maintained on an artificial larval medium its frequency rapidly rises to ≈35%. Analysis of allelic frequency trajectories have suggested strong selection in favor of heterozygotes. Here we report on the results of an extensive study designed to estimate fitness components of the various genotypes at the ADH locus and to identify the stage in the life cycle of the insect at which selection pressure is most intense. Significant differences among genotypes were observed for egg hatchability, larva-to-pupa viability, pupa-to-adult viability, and for egg-to-pupation time. When combined into an overall fitness value, these differences produced clear evidence for heterozygote advantage. In addition, our results reinforce previous claims that selection acts directly on the ADH locus and narrows the time of selection to the early larval stage. The ADH system of B. oleae serves as a model case of a predictable and drastic genetic change that occurs in an insect colony as it adapts to an artificial environment.

Evidence for Yield Stability in Selected Landraces of Bean (Phaseolus vulgaris)

SUMMARYYield stability in beans from diverse sources in Malawi was estimated using the statistical parameters of genotype X environment variance, slope and standard error from regression. The heterozygous F2 and the most complex synthetic mixture were very stable, although not significantly different from some pure genotypes. The mean yields of most mixtures were marginally higher than the average of their components. There was a linear relationship between magnitude of diversity and stability. Evidence for heterozygote advantage was demonstrated.

Population Studies in Predominantly Self-Pollinated Species, I. Evidence for Heterozygote Advantage in a Closed Population of Barley

Population Studies in Predominantly Self-Pollinated Species, I. Evidence for Heterozygote Advantage in a Closed Population of Barley