Problems with studying directional natural selection in humans Проблемы изучения направленного естественного отбора у человека
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PROVIDER: S-EPMC10643113 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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Project description:Modern molecular genetic datasets, primarily collected to study the biology of human health and disease, can be used to directly measure the action of natural selection and reveal important features of contemporary human evolution. Here we leverage the UK Biobank data to test for the presence of linear and nonlinear natural selection in a contemporary population of the United Kingdom. We obtain phenotypic and genetic evidence consistent with the action of linear/directional selection. Phenotypic evidence suggests that stabilizing selection, which acts to reduce variance in the population without necessarily modifying the population mean, is widespread and relatively weak in comparison with estimates from other species.
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Project description:Natural selection acts ubiquitously on complex human traits, predominantly constraining the occurrence of extreme phenotypes (stabilizing selection). These constraints propagate to DNA sequence variants associated with traits under selection. The genetic signatures of such evolutionary events can thus be detected via combining effect size estimates from genetic association studies and the corresponding allele frequencies. Although this approach has been successfully applied to high-level traits, the prevalence and mode of selection acting on molecular traits remain poorly understood. Here, we estimate the action of natural selection on genetic variants associated with metabolite levels, an important layer of molecular traits. By leveraging summary statistics of published genome-wide association studies with large sample sizes, we find strong evidence of stabilizing selection for 15 out of 97 plasma metabolites, with nonessential amino acids displaying especially strong selection signatures. Mendelian randomization analysis reveals that metabolites under stronger stabilizing selection display larger effects on a range of clinically relevant complex traits, suggesting that maintaining a disease-free profile may be an important source of selective constraints on the metabolome. Metabolites under strong stabilizing selection in humans are also more conserved in their concentrations among diverse mammalian species, suggesting shared selective forces across micro- and macroevolutionary timescales. Overall, this study demonstrates that variation in metabolite levels among humans is frequently shaped by natural selection and this may act through their causal impact on disease susceptibility.
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Project description:Human mtDNA shows striking regional variation, traditionally attributed to genetic drift. However, it is not easy to account for the fact that only two mtDNA lineages (M and N) left Africa to colonize Eurasia and that lineages A, C, D, and G show a 5-fold enrichment from central Asia to Siberia. As an alternative to drift, natural selection might have enriched for certain mtDNA lineages as people migrated north into colder climates. To test this hypothesis we analyzed 104 complete mtDNA sequences from all global regions and lineages. African mtDNA variation did not significantly deviate from the standard neutral model, but European, Asian, and Siberian plus Native American variations did. Analysis of amino acid substitution mutations (nonsynonymous, Ka) versus neutral mutations (synonymous, Ks) (kaks) for all 13 mtDNA protein-coding genes revealed that the ATP6 gene had the highest amino acid sequence variation of any human mtDNA gene, even though ATP6 is one of the more conserved mtDNA proteins. Comparison of the kaks ratios for each mtDNA gene from the tropical, temperate, and arctic zones revealed that ATP6 was highly variable in the mtDNAs from the arctic zone, cytochrome b was particularly variable in the temperate zone, and cytochrome oxidase I was notably more variable in the tropics. Moreover, multiple amino acid changes found in ATP6, cytochrome b, and cytochrome oxidase I appeared to be functionally significant. From these analyses we conclude that selection may have played a role in shaping human regional mtDNA variation and that one of the selective influences was climate.
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Project description:Genetic correlation between mates at specific loci can greatly alter the evolutionary trajectory of a species. Genetic assortative mating has been documented in humans, but its existence beyond population stratification (shared ancestry) has been a matter of controversy. Here, we develop a method to measure assortative mating across the genome at 1,044,854 single-nucleotide polymorphisms (SNPs), controlling for population stratification and cohort-specific cryptic relatedness. Using data on 1683 human couples from two data sources, we find evidence for both assortative and disassortative mating at specific, discernible loci throughout the entire genome. Then, using the composite of multiple signals (CMS) score, we also show that the group of SNPs exhibiting the most assortativity has been under stronger recent positive selection. Simulations using realistic inputs confirm that assortative mating might indeed affect changes in allele frequency over time. These results suggest that genetic assortative mating may be speeding up evolution in humans.
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Project description:Empowered by technology and sampling efforts designed to facilitate genome-wide association mapping, human geneticists are now studying the geography of genetic variation in unprecedented detail. With high genomic coverage and geographic resolution, these studies are identifying loci with spatial signatures of selection, such as extreme levels of differentiation and correlations with environmental variables. Collectively, patterns at these loci are beginning to provide new insights into the process of human adaptation. Here, we review the challenges of these studies and emerging results, including how human population structure has influenced the response to novel selective pressures.
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Project description:BACKGROUND:Molecular evolution is a very active field of research, with several complementary approaches, including dN/dS, HON90, MM01, and others. Each has documented strengths and weaknesses, and no one approach provides a clear picture of how natural selection works at the molecular level. The purpose of this work is to present a simple new method that uses quantitative amino acid properties to identify and characterize directional selection in proteins. METHODS:Inferred amino acid replacements are viewed through the prism of a single physicochemical property to determine the amount and direction of change caused by each replacement. This allows the calculation of the probability that the mean change in the single property associated with the amino acid replacements is equal to zero (H0: ? = 0; i.e., no net change) using a simple two-tailed t-test. RESULTS:Example data from calanoid and cyclopoid copepod cytochrome oxidase subunit I sequence pairs are presented to demonstrate how directional selection may be linked to major shifts in adaptive zones, and that convergent evolution at the whole organism level may be the result of convergent protein adaptations. CONCLUSIONS:Rather than replace previous methods, this new method further complements existing methods to provide a holistic glimpse of how natural selection shapes protein structure and function over evolutionary time.
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Project description:The olfactory receptor (OR) genes constitute the largest gene family in mammalian genomes. Humans have >1,000 OR genes, of which only approximately 40% have an intact coding region and are therefore putatively functional. In contrast, the fraction of intact OR genes in the genomes of the great apes is significantly greater (68%-72%), suggesting that selective pressures on the OR repertoire vary among these species. We have examined the evolutionary forces that shaped the OR gene family in humans and chimpanzees by resequencing 20 OR genes in 16 humans, 16 chimpanzees, and one orangutan. We compared the variation at the OR genes with that at intergenic regions. In both humans and chimpanzees, OR pseudogenes seem to evolve neutrally. In chimpanzees, patterns of variability are consistent with purifying selection acting on intact OR genes, whereas, in humans, there is suggestive evidence for positive selection acting on intact OR genes. These observations are likely due to differences in lifestyle, between humans and great apes, that have led to distinct sensory needs.
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Project description:Evolution is foundational to understanding biology, yet learners at all stages have incomplete and incorrect ideas that persist beyond graduation. Contextual features of prompts (e.g., taxon of organism, acquisition vs. loss of traits, etc.) have been shown to influence both the learning process and the ideas students express in explanations of evolutionary processes. In this study, we compare students' explanations of natural selection for humans versus a nonhuman animal (cheetah) at different times during biology instruction. We found "taxon" to be a significant predictor of the content of students' explanations. Responses to "cheetah" prompts contained a larger number and diversity of key concepts (e.g., variation, heritability, differential reproduction) and fewer naïve ideas (e.g., need, adapt) when compared with responses to an isomorphic prompt containing "human" as the organism. Overall, instruction increased the prevalence of key concepts, reduced naïve ideas, and caused a modest reduction in differences due to taxon. Our findings suggest that the students are reasoning differently about evolutionary processes in humans as compared with nonhuman animals, and that targeted instruction may both increase students' facility with key concepts while reducing their susceptibility to contextual influences.
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Project description:There are mean differences in complex traits among global human populations. We hypothesize that part of the phenotypic differentiation is due to natural selection. To address this hypothesis, we assess the differentiation in allele frequencies of trait-associated SNPs among African, Eastern Asian, and European populations for ten complex traits using data of large sample size (up to ~405,000). We show that SNPs associated with height ([Formula: see text]), waist-to-hip ratio ([Formula: see text]), and schizophrenia ([Formula: see text]) are significantly more differentiated among populations than matched "control" SNPs, suggesting that these trait-associated SNPs have undergone natural selection. We further find that SNPs associated with height ([Formula: see text]) and schizophrenia ([Formula: see text]) show significantly higher variance in linkage disequilibrium (LD) scores across populations than control SNPs. Our results support the hypothesis that natural selection has shaped the genetic differentiation of complex traits, such as height and schizophrenia, among worldwide populations.
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Project description:Individuals from different populations vary considerably in their susceptibility to immune-related diseases. To understand how genetic variation and natural selection contribute to these differences, we tested for the effects of African versus European ancestry on the transcriptional response of primary macrophages to live bacterial pathogens. 12% of macrophage-expressed genes show ancestry-associated differences in the gene regulatory response to infection, and African ancestry specifically predicts a stronger inflammatory response and reduced intracellular bacterial growth. A large proportion of these differences are under genetic control: for 569 genes, more than 75% of ancestry effects on the immune response can be explained by a single cis- or trans-acting eQTL. Finally, we show that genetic effects on the immune response are strongly enriched for recent, population-specific signatures of adaptation. Together, our results demonstrate how historical selective events continue to shape human phenotypic diversity today, including for traits that are central to coping with infection. Transcriptomic profiles of 503 infected (Listeria and Salmonella) and non-infected samples at 2hr time point.
2016-09-06 | E-GEOD-81046 | biostudies-arrayexpress