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PMID: 18464896 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

The impact of recombination on nucleotide substitutions in the human genome.

PLoS genetics ·Vol. 4 ·No. 5 ·2008-05-09 ·Pages e1000071

Duret L, Arndt PF

Abstract

Unraveling the evolutionary forces responsible for variations of neutral substitution patterns among taxa or along genomes is a major issue for detecting selection within sequences. Mammalian genomes show large-scale regional variations of GC-content (the isochores), but the substitution processes at the origin of this structure are poorly understood. We analyzed the pattern of neutral substitutions in 1 Gb of primate non-coding regions. We show that the GC-content toward which sequences are evolving is strongly negatively correlated to the distance to telomeres and positively correlated to the rate of crossovers (R2 = 47%). This demonstrates that recombination has a major impact on substitution patterns in human, driving the evolution of GC-content. The evolution of GC-content correlates much more strongly with male than with female crossover rate, which rules out selectionist models for the evolution of isochores. This effect of recombination is most probably a consequence of the neutral process of biased gene conversion (BGC) occurring within recombination hotspots. We show that the predictions of this model fit very well with the observed substitution patterns in the human genome. This model notably explains the positive correlation between substitution rate and recombination rate. Theoretical calculations indicate that variations in population size or density in recombination hotspots can have a very strong impact on the evolution of base composition. Furthermore, recombination hotspots can create strong substitution hotspots. This molecular drive affects both coding and non-coding regions. We therefore conclude that along with mutation, selection and drift, BGC is one of the major factors driving genome evolution. Our results also shed light on variations in the rate of crossover relative to non-crossover events, along chromosomes and according to sex, and also on the conservation of hotspot density between human and chimp.

MeSH Terms
Animals Base Composition Chromosomes, Human Crosses, Genetic Evolution, Molecular Female Gene Conversion Genome, Human Humans Isochores/genetics Macaca/genetics Male Models, Genetic Mutation Pan troglodytes/genetics Species Specificity Telomere
Chemicals
Isochores
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Duret Laurent
Laboratoire de Biométrie et Biologie Evolutive, Université de Lyon, Université Lyon 1, CNRS, UMR 5558, Villeurbanne, France. duret@biomserv.univ-lyon1.fr
Arndt Peter F
Conflict of Interest

The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1000071
Email
duret@biomserv.univ-lyon1.fr
Published
2008-05-09
Epub
2008-00-09
Pages
e1000071
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2346554
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pgen.1000071 PMC Full Text View journal details
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