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, Jorgensen, Torben, Jiang, Tao, Witte, Daniel R., Sandbaek, Annelli, Hellmann, Ines, Lauritzen, Torsten, Hansen, Torben, Pedersen, Oluf, Wang, Jun and Nielsen, Rasmus (2011) Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome. PLoS Genetics, 7 10: 67-74. doi:10.1371/journal.pgen.1002326

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
Jorgensen, Torben
Jiang, Tao
Witte, Daniel R.
Sandbaek, Annelli
Hellmann, Ines
Lauritzen, Torsten
Hansen, Torben
Pedersen, Oluf
Wang, Jun
Nielsen, Rasmus
Title Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7390
Publication date 2011-10-13
Year available 2011
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1002326
Open Access Status DOI
Volume 7
Issue 10
Start page 67
End page 74
Total pages 15
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Abstract 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.
Keyword Psychology, Developmental
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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