A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes

GC-biased gene conversion (gBGC) is a recombination-associated process that favors the fixation of G/C alleles over A/T alleles. In mammals, gBGC is hypothesized to contribute to variation in GC content, rapidly evolving sequences, and the fixation of deleterious mutations, but its prevalence and ge...

Full description

Bibliographic Details
Main Authors:	Capra, John A., Hubisz, Melissa J., Kostka, Dennis, Pollard, Katherine S., Siepel, Adam
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744432/

id	pubmed-3744432
recordtype	oai_dc
spelling	pubmed-37444322013-08-21 A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes Capra, John A. Hubisz, Melissa J. Kostka, Dennis Pollard, Katherine S. Siepel, Adam Research Article GC-biased gene conversion (gBGC) is a recombination-associated process that favors the fixation of G/C alleles over A/T alleles. In mammals, gBGC is hypothesized to contribute to variation in GC content, rapidly evolving sequences, and the fixation of deleterious mutations, but its prevalence and general functional consequences remain poorly understood. gBGC is difficult to incorporate into models of molecular evolution and so far has primarily been studied using summary statistics from genomic comparisons. Here, we introduce a new probabilistic model that captures the joint effects of natural selection and gBGC on nucleotide substitution patterns, while allowing for correlations along the genome in these effects. We implemented our model in a computer program, called phastBias, that can accurately detect gBGC tracts about 1 kilobase or longer in simulated sequence alignments. When applied to real primate genome sequences, phastBias predicts gBGC tracts that cover roughly 0.3% of the human and chimpanzee genomes and account for 1.2% of human-chimpanzee nucleotide differences. These tracts fall in clusters, particularly in subtelomeric regions; they are enriched for recombination hotspots and fast-evolving sequences; and they display an ongoing fixation preference for G and C alleles. They are also significantly enriched for disease-associated polymorphisms, suggesting that they contribute to the fixation of deleterious alleles. The gBGC tracts provide a unique window into historical recombination processes along the human and chimpanzee lineages. They supply additional evidence of long-term conservation of megabase-scale recombination rates accompanied by rapid turnover of hotspots. Together, these findings shed new light on the evolutionary, functional, and disease implications of gBGC. The phastBias program and our predicted tracts are freely available. Public Library of Science 2013-08-15 /pmc/articles/PMC3744432/ /pubmed/23966869 http://dx.doi.org/10.1371/journal.pgen.1003684 Text en © 2013 Capra et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Capra, John A. Hubisz, Melissa J. Kostka, Dennis Pollard, Katherine S. Siepel, Adam
spellingShingle	Capra, John A. Hubisz, Melissa J. Kostka, Dennis Pollard, Katherine S. Siepel, Adam A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes
author_facet	Capra, John A. Hubisz, Melissa J. Kostka, Dennis Pollard, Katherine S. Siepel, Adam
author_sort	Capra, John A.
title	A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes
title_short	A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes
title_full	A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes
title_fullStr	A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes
title_full_unstemmed	A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes
title_sort	model-based analysis of gc-biased gene conversion in the human and chimpanzee genomes
description	GC-biased gene conversion (gBGC) is a recombination-associated process that favors the fixation of G/C alleles over A/T alleles. In mammals, gBGC is hypothesized to contribute to variation in GC content, rapidly evolving sequences, and the fixation of deleterious mutations, but its prevalence and general functional consequences remain poorly understood. gBGC is difficult to incorporate into models of molecular evolution and so far has primarily been studied using summary statistics from genomic comparisons. Here, we introduce a new probabilistic model that captures the joint effects of natural selection and gBGC on nucleotide substitution patterns, while allowing for correlations along the genome in these effects. We implemented our model in a computer program, called phastBias, that can accurately detect gBGC tracts about 1 kilobase or longer in simulated sequence alignments. When applied to real primate genome sequences, phastBias predicts gBGC tracts that cover roughly 0.3% of the human and chimpanzee genomes and account for 1.2% of human-chimpanzee nucleotide differences. These tracts fall in clusters, particularly in subtelomeric regions; they are enriched for recombination hotspots and fast-evolving sequences; and they display an ongoing fixation preference for G and C alleles. They are also significantly enriched for disease-associated polymorphisms, suggesting that they contribute to the fixation of deleterious alleles. The gBGC tracts provide a unique window into historical recombination processes along the human and chimpanzee lineages. They supply additional evidence of long-term conservation of megabase-scale recombination rates accompanied by rapid turnover of hotspots. Together, these findings shed new light on the evolutionary, functional, and disease implications of gBGC. The phastBias program and our predicted tracts are freely available.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744432/
_version_	1612003331196059648

A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes

Similar Items