Sexual selection and inbreeding: Two efficient ways to limit the accumulation of deleterious mutations.
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ABSTRACT:
SUBMITTER: Noel E
PROVIDER: S-EPMC6369961 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Each individual has a certain number of harmful mutations in its genome. These mutations can lower the fitness of the individual carrying them, dependent on their dominance and selection coefficient. Effective population size, selection, and admixture are known to affect the occurrence of such mutations in a population. The relative roles of demography and selection are a key in understanding the process of adaptation. These are factors that are potentially influenced and confounded in domestic animals. Here, we hypothesize that the series of events of bottlenecks, introgression, and strong artificial selection associated with domestication increased mutational load in domestic species. Yet, mutational load is hard to quantify, so there are very few studies available revealing the relevance of evolutionary processes. The precise role of artificial selection, bottlenecks, and introgression in further increasing the load of deleterious variants in animals in breeding and conservation programmes remains unclear. In this paper, we review the effects of domestication and selection on mutational load in domestic species. Moreover, we test some hypotheses on higher mutational load due to domestication and selective sweeps using sequence data from commercial pig and chicken lines. Overall, we argue that domestication by itself is not a prerequisite for genetic erosion, indicating that fitness potential does not need to decline. Rather, mutational load in domestic species can be influenced by many factors, but consistent or strong trends are not yet clear. However, methods emerging from molecular genetics allow discrimination of hypotheses about the determinants of mutational load, such as effective population size, inbreeding, and selection, in domestic systems. These findings make us rethink the effect of our current breeding schemes on fitness of populations.
| S-EPMC6304688 | biostudies-literature
Project description:Free-living bacteria are usually thought to have large effective population sizes, and so tiny selective differences can drive their evolution. However, because recombination is infrequent, "background selection" against slightly deleterious alleles should reduce the effective population size (Ne) by orders of magnitude. For example, for a well-mixed population with 10(12) individuals and a typical level of homologous recombination (r/m = 3, i.e., nucleotide changes due to recombination [r] occur at 3 times the mutation rate [m]), we predict that Ne is <10(7). An argument for high Ne values for bacteria has been the high genetic diversity within many bacterial "species," but this diversity may be due to population structure: diversity across subpopulations can be far higher than diversity within a subpopulation, which makes it difficult to estimate Ne correctly. Given an estimate of Ne, standard population genetics models imply that selection should be sufficient to drive evolution if Ne × s is >1, where s is the selection coefficient. We found that this remains approximately correct if background selection is occurring or when population structure is present. Overall, we predict that even for free-living bacteria with enormous populations, natural selection is only a significant force if s is above 10(-7) or so.Because bacteria form huge populations with trillions of individuals, the simplest theoretical prediction is that the better allele at a site would predominate even if its advantage was just 10(-9) per generation. In other words, virtually every nucleotide would be at the local optimum in most individuals. A more sophisticated theory considers that bacterial genomes have millions of sites each and selection events on these many sites could interfere with each other, so that only larger effects would be important. However, bacteria can exchange genetic material, and in principle, this exchange could eliminate the interference between the evolution of the sites. We used simulations to confirm that during multisite evolution with realistic levels of recombination, only larger effects are important. We propose that advantages of less than 10(-7) are effectively neutral.
| S-EPMC4701828 | biostudies-other
Project description:Epistasis may have important consequences for a number of issues in quantitative genetics and evolutionary biology. In particular, synergistic epistasis for deleterious alleles is relevant to the mutation load paradox and the evolution of sex and recombination. Some studies have shown evidence of synergistic epistasis for spontaneous or induced deleterious mutations appearing in mutation-accumulation experiments. However, many newly arising mutations may not actually be segregating in natural populations because of the erasing action of natural selection. A demonstration of synergistic epistasis for naturally segregating alleles can be achieved by means of inbreeding depression studies, as deleterious recessive allelic effects are exposed in inbred lines. Nevertheless, evidence of epistasis from these studies is scarce and controversial. In this paper, we report the results of two independent inbreeding experiments carried out with two different populations of Drosophila melanogaster. The results show a consistent accelerated inbreeding depression for fitness, suggesting synergistic epistasis among deleterious alleles. We also performed computer simulations assuming different possible models of epistasis and mutational parameters for fitness, finding some of them to be compatible with the results observed. Our results suggest that synergistic epistasis for deleterious mutations not only occurs among newly arisen spontaneous or induced mutations, but also among segregating alleles in natural populations.
| S-EPMC6834575 | biostudies-literature
Project description:Island colonizations are excellent models for studying early processes of evolution. We found in a previous study on mice that had colonized the sub-Antarctic Kerguelen Archipelago about 200 years ago that they were derived from a single founder lineage and that this showed an unexpectedly large number of new mutations in the mitochondrial D-loop. To assess whether positive selection has played a role in the emergence of these variants, we have obtained 16 full mitochondrial genome sequences from these mice. For comparison, we have compiled 57 mitochondrial genome sequences from laboratory inbred lines that became established about 100 years ago, also starting from a single founder lineage. We find that the island mice and the laboratory lines show very similar mutation frequencies and patterns. None of the patterns in the Kerguelen mice provides evidence for positive selection. We conclude that nearly neutral evolutionary processes that assume the presence of slightly deleterious variants can fully explain the patterns. This supports the notion of time-dependency of molecular evolution and provides a new calibration point. Based on the observed mutation frequency, we calculate an average evolutionary rate of 0.23 substitutions per site per Myr for the earliest time frame of divergence, which is about six times higher than the long-term rate of 0.037 substitutions per site per Myr.
| S-EPMC3639765 | biostudies-literature
Project description:Recent theory predicts that the fitness of pioneer populations can decline when species expand their range, due to high rates of genetic drift on wave fronts making selection less efficient at purging deleterious variants. To test these predictions, we studied the fate of mutator bacteria expanding their range for 1650 generations on agar plates. In agreement with theory, we find that growth abilities of strains with a high mutation rate (HMR lines) decreased significantly over time, unlike strains with a lower mutation rate (LMR lines) that present three to four times fewer mutations. Estimation of the distribution of fitness effect under a spatially explicit model reveals a mean negative effect for new mutations (-0.38%), but it suggests that both advantageous and deleterious mutations have accumulated during the experiment. Furthermore, the fitness of HMR lines measured in different environments has decreased relative to the ancestor strain, whereas that of LMR lines remained unchanged. Contrastingly, strains with a HMR evolving in a well-mixed environment accumulated less mutations than agar-evolved strains and showed an increased fitness relative to the ancestor. Our results suggest that spatially expanding species are affected by deleterious mutations, leading to a drastic impairment of their evolutionary potential.
| S-EPMC5629331 | biostudies-literature
Project description:Colonization of new habitats often reduces population sizes and may result in the accumulation of deleterious mutations by genetic drift. Compared with the genomic basis for adaptation to new environments, genome-wide analysis of deleterious mutations in isolated populations remains limited. In the present study, we investigated the accumulation of deleterious mutations in five endangered freshwater populations of threespine stickleback (Gasterosteus aculeatus) in the central part of the mainland of Japan. Using whole-genome resequencing data, we first conducted phylogenomic analysis and confirmed at least two independent freshwater colonization events in the central mainland from ancestral marine ecotypes. Next, analyses of single nucleotide polymorphisms showed a substantial reduction of heterozygosity in freshwater populations compared with marine populations. Reduction in heterozygosity was more apparent at the center of each chromosome than the peripheries and on X chromosomes compared with autosomes. Third, bioinformatic analysis of deleterious mutations showed increased accumulation of putatively deleterious mutations in the landlocked freshwater populations compared with marine populations. For the majority of populations examined, the frequencies of putatively deleterious mutations were higher on X chromosomes than on autosomes. The interpopulation comparison indicated that the majority of putatively deleterious mutations may have accumulated independently. Thus, whole-genome resequencing of endangered populations can help to estimate the accumulation of deleterious mutations and inform us of which populations are the most severely endangered. Furthermore, analysis of variation among chromosomes can give insights into whether any particular chromosomes are likely to accumulate deleterious mutations.
| S-EPMC7197494 | biostudies-literature
Project description:For aging to evolve, selection against mortality must decrease with age. This prevailing view in the evolutionary theory of senescence posits that mutations with deleterious effects happening late in life-when purging selection is weak-may become fixed via genetic drift in the germline, and produce a senescent phenotype. Theory, however, has focused primarily on growing populations and the fate of single deleterious mutations. In a mathematical model, we demonstrate that relaxing both of these simplifying assumptions leads to unrealistic outcomes. In density-regulated populations, previously fixed deleterious mutations should promote the fixation of other deleterious mutations that lead to senescence at ever younger ages, until death necessarily occurs at sexual maturity. This sequential fixation of deleterious mutations is not promoted by a decrease in population size, but is due to a change in the strength of selection. In an individual-based model, we also show that such evolutionary dynamics should lead to the extinction of most populations. Our models therefore make rather unrealistic predictions, underlining the need for a reappraisal of current theories. In this respect, we have further assumed in our models that the deleterious effects of mutations can only occur at certain ages, marked, for instance, by somatic or physiological changes. Under this condition, we show that the catastrophic accumulation of deleterious mutations in the germline can stop. This new finding emphasizes the importance of investigating somatic factors, as well as other mechanisms underlying the deleterious effects of mutations, to understand senescence evolution. More generally, our model therefore establishes that patterns of senescence in nature depend not only on the decrease in selection strength with age but also on any mechanism that stops the catastrophic accumulation of mutations.
| S-EPMC10959475 | biostudies-literature
Project description:Human-driven habitat fragmentation and loss have led to a proliferation of small and isolated plant and animal populations with high risk of extinction. One of the main threats to extinction in these populations is inbreeding depression, which is primarily caused by recessive deleterious mutations becoming homozygous due to inbreeding. The typical approach for managing these populations is to maintain high genetic diversity, increasingly by translocating individuals from large populations to initiate a "genetic rescue." However, the limitations of this approach have recently been highlighted by the demise of the gray wolf population on Isle Royale, which declined to the brink of extinction soon after the arrival of a migrant from the large mainland wolf population. Here, we use a novel population genetic simulation framework to investigate the role of genetic diversity, deleterious variation, and demographic history in mediating extinction risk due to inbreeding depression in small populations. We show that, under realistic models of dominance, large populations harbor high levels of recessive strongly deleterious variation due to these mutations being hidden from selection in the heterozygous state. As a result, when large populations contract, they experience a substantially elevated risk of extinction after these strongly deleterious mutations are exposed by inbreeding. Moreover, we demonstrate that, although genetic rescue is broadly effective as a means to reduce extinction risk, its effectiveness can be greatly increased by drawing migrants from small or moderate-sized source populations rather than large source populations due to smaller populations harboring lower levels of recessive strongly deleterious variation. Our findings challenge the traditional conservation paradigm that focuses on maximizing genetic diversity in small populations in favor of a view that emphasizes minimizing strongly deleterious variation. These insights have important implications for managing small and isolated populations in the increasingly fragmented landscape of the Anthropocene.
| S-EPMC7857301 | biostudies-literature
Project description:The deleterious effects of inbreeding have been of extreme importance to evolutionary biology, but it has been difficult to characterize the complex interactions between genetic constraints and selection that lead to fitness loss and recovery after inbreeding. Haploid organisms and selfing organisms like the nematode Caenorhabditis elegans are capable of rapid recovery from the fixation of novel deleterious mutation; however, the potential for recovery and genomic consequences of inbreeding in diploid, outcrossing organisms are not well understood. We sought to answer two questions: 1) Can a diploid, outcrossing population recover from inbreeding via standing genetic variation and new mutation? and 2) How does allelic diversity change during recovery? We inbred C. remanei, an outcrossing relative of C. elegans, through brother-sister mating for 30 generations followed by recovery at large population size. Inbreeding reduced fitness but, surprisingly, recovery from inbreeding at large populations sizes generated only very moderate fitness recovery after 300 generations. We found that 65% of ancestral single nucleotide polymorphisms (SNPs) were fixed in the inbred population, far fewer than the theoretical expectation of ∼99%. Under recovery, 36 SNPs across 30 genes involved in alimentary, muscular, nervous, and reproductive systems changed reproducibly across replicates, indicating that strong selection for fitness recovery does exist. Our results indicate that recovery from inbreeding depression via standing genetic variation and mutation is likely to be constrained by the large number of segregating deleterious variants present in natural populations, limiting the capacity for recovery of small populations.
| S-EPMC8789292 | biostudies-literature
Project description:We have previously proposed that selective inheritance, the limited transmission of damaging mtDNA mutations from mother to offspring, is based on replication competition in Drosophila melanogaster. This model, which stems from our observation that wild-type mitochondria propagate much more vigorously in the fly ovary than mitochondria carrying fitness-impairing mutations, implies that germ cells recognize the fitness of individual mitochondria and selectively boost the propagation of healthy ones. Here, we demonstrate that the protein kinase PINK1 preferentially accumulates on mitochondria enriched for a deleterious mtDNA mutation. PINK1 phosphorylates Larp to inhibit protein synthesis on the mitochondrial outer membrane. Impaired local translation on defective mitochondria in turn limits the replication of their mtDNA and hence the transmission of deleterious mutations to the offspring. Our work confirms that selective inheritance occurs at the organelle level during Drosophila oogenesis and provides molecular entry points to test this model in other systems.
| S-EPMC7485087 | biostudies-literature