Titel
Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome
Autor*in
Kirk E. Lohmueller
Department of Integrative Biology
Autor*in
Anders Albrechtsen
University of Copenhagen
Autor*in
Yingrui Li
BGI-Shenzhen
... show all
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.
Stichwort
ANCESTRAL POPULATION SIZESSINGLE-NUCLEOTIDE POLYMORPHISMSGENERATION SEQUENCING DATAALLELE FREQUENCY-SPECTRUMRECENT POSITIVE SELECTIONDROSOPHILA-MELANOGASTERBACKGROUND SELECTIONRECOMBINATION RATESDNA POLYMORPHISMDELETERIOUS MUTATIONS
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
https://phaidra.univie.ac.at/o:245487
Erschienen in
Titel
PLoS Genetics
Band
7
Ausgabe
10
Seitenanfang
e1002326
Erscheinungsdatum
01.02.2011
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