Dominance of Deleterious Alleles Controls the Response to a Population Bottleneck.
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ABSTRACT:
SUBMITTER: Balick DJ
PROVIDER: S-EPMC4552954 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Deleterious alleles have long been proposed to play an important role in patterning phenotypic variation and are central to commonly held ideas explaining the hybrid vigor observed in the offspring of a cross between two inbred parents. We test these ideas using evolutionary measures of sequence conservation to ask whether incorporating information about putatively deleterious alleles can inform genomic selection (GS) models and improve phenotypic prediction. We measured a number of agronomic traits in both the inbred parents and hybrids of an elite maize partial diallel population and re-sequenced the parents of the population. Inbred elite maize lines vary for more than 350,000 putatively deleterious sites, but show a lower burden of such sites than a comparable set of traditional landraces. Our modeling reveals widespread evidence for incomplete dominance at these loci, and supports theoretical models that more damaging variants are usually more recessive. We identify haplotype blocks using an identity-by-decent (IBD) analysis and perform genomic prediction analyses in which we weigh blocks on the basis of complementation for segregating putatively deleterious variants. Cross-validation results show that incorporating sequence conservation in genomic selection improves prediction accuracy for grain yield and other fitness-related traits as well as heterosis for those traits. Our results provide empirical support for an important role for incomplete dominance of deleterious alleles in explaining heterosis and demonstrate the utility of incorporating functional annotation in phenotypic prediction and plant breeding.
| S-EPMC5633198 | biostudies-literature
Project description:[This corrects the article DOI: 10.1371/journal.pgen.1007019.].
| S-EPMC8478179 | biostudies-literature
Project description:Background:In the classical psychological refractory period (PRP) paradigm, two stimuli are presented in brief succession, and participants are asked to make separate speeded responses to both stimuli. Due to a central cognitive bottleneck, responses to the second stimulus are delayed, especially at short stimulus-onset asynchrony (SOA) between the two stimuli. Although the mechanisms of dual-task interference in the classical PRP paradigm have been extensively investigated, specific mechanisms underlying the cross-modal PRP paradigm are not well understood. In particular, it remains unknown whether the dominance of vision over audition manifests in the cross-modal PRP tasks. The present study aimed to investigate whether the visual dominance effect manifests in the cross-modal PRP paradigm. Methods:We adapted the classical PRP paradigm by manipulating the order of a visual and an auditory task: the visual task could either precede the auditory task or vice versa, at either short or long SOAs. Twenty-five healthy participants took part in Experiment 1, and thirty-three new participants took part in Experiment 2. Reaction time and accuracy data were calculated and further analyzed by repeated-measures analysis of variance. Results:The results showed that visual precedence in the Visual-Auditory condition caused larger impairments to the subsequent auditory processing than vice versa in the Auditory-Visual condition: a larger delay of second response was revealed in the Visual-Auditory condition (135 ± 10 ms) than the Auditory-Visual condition (88 ± 9 ms). This effect was found only at the short SOAs under the existence of the central bottleneck, but not at the long SOAs. Moreover, this effect occurred both when the single visual and the single auditory task were of equal difficulty in Experiment 1 and when the single auditory task was more difficult than the single visual task in Experiment 2. Conclusion:Results of the two experiments suggested that the visual dominance effect occurred under the central bottleneck of cognitive processing.
| S-EPMC6085859 | biostudies-other
Project description:The genetic consequences of population bottlenecks on patterns of deleterious genetic variation in human populations are of tremendous interest. Based on exome sequencing of 18 Greenlandic Inuit we show that the Inuit have undergone a severe ∼20,000-year-long bottleneck. This has led to a markedly more extreme distribution of allele frequencies than seen for any other human population tested to date, making the Inuit the perfect population for investigating the effect of a bottleneck on patterns of deleterious variation. When comparing proxies for genetic load that assume an additive effect of deleterious alleles, the Inuit show, at most, a slight increase in load compared to European, East Asian, and African populations. Specifically, we observe <4% increase in the number of derived deleterious alleles in the Inuit. In contrast, proxies for genetic load under a recessive model suggest that the Inuit have a significantly higher load (20% increase or more) compared to other less bottlenecked human populations. Forward simulations under realistic models of demography support our empirical findings, showing up to a 6% increase in the genetic load for the Inuit population across all models of dominance. Further, the Inuit population carries fewer deleterious variants than other human populations, but those that are present tend to be at higher frequency than in other populations. Overall, our results show how recent demographic history has affected patterns of deleterious variants in human populations.
| S-EPMC5289852 | biostudies-literature
Project description:BACKGROUND:In this paper, we simulate deleterious load in an animal breeding program, and compare the efficiency of genome editing and selection for decreasing it. Deleterious variants can be identified by bioinformatics screening methods that use sequence conservation and biological prior information about protein function. However, once deleterious variants have been identified, how can they be used in breeding? RESULTS:We simulated a closed animal breeding population that is subject to both natural selection against deleterious load and artificial selection for a quantitative trait representing the breeding goal. Deleterious load was polygenic and was due to either codominant or recessive variants. We compared strategies for removal of deleterious alleles by genome editing (RAGE) to selection against carriers. When deleterious variants were codominant, the best strategy for prioritizing variants was to prioritize low-frequency variants. When deleterious variants were recessive, the best strategy was to prioritize variants with an intermediate frequency. Selection against carriers was inefficient when variants were codominant, but comparable to editing one variant per sire when variants were recessive. CONCLUSIONS:Genome editing of deleterious alleles reduces deleterious load, but requires the simultaneous editing of multiple deleterious variants in the same sire to be effective when deleterious variants are recessive. In the short term, selection against carriers is a possible alternative to genome editing when variants are recessive. Our results suggest that, in the future, there is the potential to use RAGE against deleterious load in animal breeding.
| S-EPMC6472060 | biostudies-literature
Project description:Recessive deleterious mutations are common, causing many genetic disorders in humans and producing inbreeding depression in the majority of sexually reproducing diploids. The abundance of recessive deleterious mutations in natural populations suggests they are likely to be present on a chromosome when a new adaptive mutation occurs, yet the dynamics of recessive deleterious hitchhikers and their impact on adaptation remains poorly understood. Here we model how a recessive deleterious mutation impacts the fate of a genetically linked dominant beneficial mutation. The frequency trajectory of the adaptive mutation in this case is dramatically altered and results in what we have termed a "staggered sweep." It is named for its three-phased trajectory: (i) Initially, the two linked mutations have a selective advantage while rare and will increase in frequency together, then (ii), at higher frequencies, the recessive hitchhiker is exposed to selection and can cause a balanced state via heterozygote advantage (the staggered phase), and (iii) finally, if recombination unlinks the two mutations, then the beneficial mutation can complete the sweep to fixation. Using both analytics and simulations, we show that strongly deleterious recessive mutations can substantially decrease the probability of fixation for nearby beneficial mutations, thus creating zones in the genome where adaptation is suppressed. These mutations can also significantly prolong the number of generations a beneficial mutation takes to sweep to fixation, and cause the genomic signature of selection to resemble that of soft or partial sweeps. We show that recessive deleterious variation could impact adaptation in humans and Drosophila.
| S-EPMC4443376 | biostudies-literature
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:Predictions about the consequences of a small population size on genetic and deleterious variation are fundamental to population genetics. As small populations are more affected by genetic drift, purifying selection acting against deleterious alleles is predicted to be less efficient, therefore increasing the risk of inbreeding depression. However, the extent to which small populations are subjected to genetic drift depends on the nature and time frame in which the bottleneck occurs. Domesticated species are an excellent model to investigate the consequences of population bottlenecks on genetic and deleterious variation in small populations. This is because their history is dominated by known bottlenecks associated with domestication, breed formation and intense selective breeding. Here, we use whole-genome sequencing data from 97 chickens representing 39 traditional fancy breeds to directly examine the consequences of two types of bottlenecks for deleterious variation: the severe domestication bottleneck and the recent population decline accompanying breed formation. We find that recently bottlenecked populations have a higher proportion of deleterious variants relative to populations that have been kept at small population sizes since domestication. We also observe that long tracts of homozygous genotypes (runs of homozygosity) are proportionally more enriched in deleterious variants than the rest of the genome. This enrichment is particularly evident in recently bottlenecked populations, suggesting that homozygosity of these variants is likely to occur due to genetic drift and recent inbreeding. Our results indicate that the timing and nature of population bottlenecks can substantially shape the deleterious variation landscape in small populations.
| S-EPMC6976952 | biostudies-literature
Project description:Dominance refers to the effect of a heterozygous genotype relative to that of the two homozygous genotypes. The degree of dominance of mutations for fitness can have a profound impact on how deleterious and beneficial mutations change in frequency over time as well as on the patterns of linked neutral genetic variation surrounding such selected alleles. Since dominance is such a fundamental concept, it has received immense attention throughout the history of population genetics. Early work from Fisher, Wright, and Haldane focused on understanding the conceptual basis for why dominance exists. More recent work has attempted to test these theories and conceptual models by estimating dominance effects of mutations. However, estimating dominance coefficients has been notoriously challenging and has only been done in a few species in a limited number of studies. In this review, we first describe some of the early theoretical and conceptual models for understanding the mechanisms for the existence of dominance. Second, we discuss several approaches used to estimate dominance coefficients and summarize estimates of dominance coefficients. We note trends that have been observed across species, types of mutations, and functional categories of genes. By comparing estimates of dominance coefficients for different types of genes, we test several hypotheses for the existence of dominance. Lastly, we discuss how dominance influences the dynamics of beneficial and deleterious mutations in populations and how the degree of dominance of deleterious mutations influences the impact of inbreeding on fitness.
| S-EPMC11306932 | biostudies-literature
Project description:UnlabelledA small number of African green monkeys (AGMs) were introduced into the Caribbean from West Africa in the 1600s. To determine the impact of this population bottleneck on the AGM virome, we used metagenomics to compare the viral nucleic acids in the plasma of 43 wild AGMs from West Africa (Gambia) to those in 44 AGMs from the Caribbean (St. Kitts and Nevis). Three viruses were detected in the blood of Gambian primates: simian immunodeficiency virus (SIVagm; in 42% of animals), a novel simian pegivirus (SPgVagm; in 7% of animals), and numerous novel simian anelloviruses (in 100% of animals). Only anelloviruses were detected in the Caribbean AGMs with a prevalence and levels of viral genetic diversity similar to those in the Gambian animals. A host population bottleneck therefore resulted in the exclusion of adult-acquired SIV and pegivirus from the Caribbean AGMs. The successful importation of AGM anelloviruses into the Caribbean may be the result of their early transmission to infants, very high prevalence in African AGMs, and frequent coinfections with as many as 11 distinct variants.ImportanceThe extent to which viruses can persist in small isolated populations depends on multiple host, viral, and environmental factors. The absence of prior infections may put an immunologically naive population at risk for disease outbreaks. Isolated populations originating from a small number of founder individuals are therefore considered at increased risk following contact with populations with a greater variety of viruses. Here, we compared the plasma virome of West African green monkeys to that in their descendants after importation of a small number of animals to the Caribbean. A lentivirus and a pegivirus were found in the West African population but not in the Caribbean population. Highly diverse anelloviruses were found in both populations. A small founder population, limited to infants and young juvenile monkeys, may have eliminated the sexually transmitted viruses from the Caribbean AGMs, while anelloviruses, acquired at an earlier age, persisted through the host population bottleneck.
| S-EPMC4524239 | biostudies-literature