Journal article Open Access

Current relaxation of selection on the human genome: Tolerance of deleterious mutations on olfactory receptors

Pierron, Denis; Cortés, Nicolás Gutiérrez; Letellier, Thierry; Grossman, Lawrence I.


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        <foaf:name>Pierron, Denis</foaf:name>
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        <foaf:name>Cortés, Nicolás Gutiérrez</foaf:name>
        <foaf:givenName>Nicolás Gutiérrez</foaf:givenName>
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        <foaf:name>Letellier, Thierry</foaf:name>
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        <foaf:name>Grossman, Lawrence I.</foaf:name>
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    <dct:title>Current relaxation of selection on the human genome: Tolerance of deleterious mutations on olfactory receptors</dct:title>
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    <dct:issued rdf:datatype="http://www.w3.org/2001/XMLSchema#gYear">2013</dct:issued>
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    <dct:description>Knowledge and understanding about the selective pressures that have shaped present human genetic diversity have dramatically increased in the last few years in parallel with the availability of large geno- mic datasets. The release of large datasets composed of millions of SNPs across hundreds of genomes by HAPMAP, the Human Genome Diversity Panel, and other projects has led to considerable effort to detect selection signals across the nuclear genome (Coop et al., 2009; Lopez Herraez et al., 2009; Sabeti et al., 2006, 2007; Voight et al., 2006). Most of the research has focused on positive selection forces although other selective forces, such as negative selection, may have played a substantive role on the shape of our genome. Here we studied the selective strengths acting presently on the genome by making compu- tational predictions of the pathogenicity of nonsynonymous protein mutations and interpreting the dis- tribution of scores in terms of selection. We could show that the genetic diversity for all the major pathways is still constrained by negative selection in all 11 human populations studied. In a single excep- tion, we observed a relaxation of negative selection acting on olfactory receptors. Since a decreased num- ber of functioning olfactory receptors in human compared with other primates had already been shown, this suggests that the role of olfactory receptors for survival and reproductive success has decreased dur- ing human evolution. By showing that negative selection is still relaxed, the present results imply that no plateau of minimal function has yet been reached in modern humans and therefore that olfactory capa- bility might still be decreasing. This is a first clue to present human evolution.</dct:description>
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