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Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome
A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of g...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192825/ https://www.ncbi.nlm.nih.gov/pubmed/22022285 http://dx.doi.org/10.1371/journal.pgen.1002326 |
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author | Lohmueller, Kirk E. Albrechtsen, Anders Li, Yingrui Kim, Su Yeon Korneliussen, Thorfinn Vinckenbosch, Nicolas Tian, Geng Huerta-Sanchez, Emilia Feder, Alison F. Grarup, Niels Jørgensen, Torben Jiang, Tao Witte, Daniel R. Sandbæk, Annelli Hellmann, Ines Lauritzen, Torsten Hansen, Torben Pedersen, Oluf Wang, Jun Nielsen, Rasmus |
author_facet | Lohmueller, Kirk E. Albrechtsen, Anders Li, Yingrui Kim, Su Yeon Korneliussen, Thorfinn Vinckenbosch, Nicolas Tian, Geng Huerta-Sanchez, Emilia Feder, Alison F. Grarup, Niels Jørgensen, Torben Jiang, Tao Witte, Daniel R. Sandbæk, Annelli Hellmann, Ines Lauritzen, Torsten Hansen, Torben Pedersen, Oluf Wang, Jun Nielsen, Rasmus |
author_sort | Lohmueller, Kirk E. |
collection | PubMed |
description | A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations. |
format | Online Article Text |
id | pubmed-3192825 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31928252011-10-21 Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome Lohmueller, Kirk E. Albrechtsen, Anders Li, Yingrui Kim, Su Yeon Korneliussen, Thorfinn Vinckenbosch, Nicolas Tian, Geng Huerta-Sanchez, Emilia Feder, Alison F. Grarup, Niels Jørgensen, Torben Jiang, Tao Witte, Daniel R. Sandbæk, Annelli Hellmann, Ines Lauritzen, Torsten Hansen, Torben Pedersen, Oluf Wang, Jun Nielsen, Rasmus PLoS Genet Research Article A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations. Public Library of Science 2011-10-13 /pmc/articles/PMC3192825/ /pubmed/22022285 http://dx.doi.org/10.1371/journal.pgen.1002326 Text en Lohmueller et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lohmueller, Kirk E. Albrechtsen, Anders Li, Yingrui Kim, Su Yeon Korneliussen, Thorfinn Vinckenbosch, Nicolas Tian, Geng Huerta-Sanchez, Emilia Feder, Alison F. Grarup, Niels Jørgensen, Torben Jiang, Tao Witte, Daniel R. Sandbæk, Annelli Hellmann, Ines Lauritzen, Torsten Hansen, Torben Pedersen, Oluf Wang, Jun Nielsen, Rasmus Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome |
title | Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome |
title_full | Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome |
title_fullStr | Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome |
title_full_unstemmed | Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome |
title_short | Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome |
title_sort | natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192825/ https://www.ncbi.nlm.nih.gov/pubmed/22022285 http://dx.doi.org/10.1371/journal.pgen.1002326 |
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