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Annu Rev Genomics Hum Genet. 2009;10:285-311. doi: 10.1146/annurev-genom-082908-150001.

Biased gene conversion and the evolution of mammalian genomic landscapes.

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Université de Lyon 1, CNRS, UMR5558, Laboratoire de Biométrie et Biologie Evolutive, F-69622, Villeurbanne, France.


Recombination is typically thought of as a symmetrical process resulting in large-scale reciprocal genetic exchanges between homologous chromosomes. Recombination events, however, are also accompanied by short-scale, unidirectional exchanges known as gene conversion in the neighborhood of the initiating double-strand break. A large body of evidence suggests that gene conversion is GC-biased in many eukaryotes, including mammals and human. AT/GC heterozygotes produce more GC- than AT-gametes, thus conferring a population advantage to GC-alleles in high-recombining regions. This apparently unimportant feature of our molecular machinery has major evolutionary consequences. Structurally, GC-biased gene conversion explains the spatial distribution of GC-content in mammalian genomes-the so-called isochore structure. Functionally, GC-biased gene conversion promotes the segregation and fixation of deleterious AT --> GC mutations, thus increasing our genomic mutation load. Here we review the recent evidence for a GC-biased gene conversion process in mammals, and its consequences for genomic landscapes, molecular evolution, and human functional genomics.

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