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Plos Biology : Hotspots of Biased Nucleotide Substitutions in Human Genes, Volume 7

By Hurst, Laurence D.

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Book Id: WPLBN0003930783
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Biology : Hotspots of Biased Nucleotide Substitutions in Human Genes, Volume 7  
Author: Hurst, Laurence D.
Volume: Volume 7
Language: English
Subject: Journals, Science, Biology
Collections: Periodicals: Journal and Magazine Collection, PLoS Biology
Publication Date:
Publisher: Plos


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Hurst, L. D. (n.d.). Plos Biology : Hotspots of Biased Nucleotide Substitutions in Human Genes, Volume 7. Retrieved from

Description : Genes that have experienced accelerated evolutionary rates on the human lineage during recent evolution are candidates for involvement in human-specific adaptations. To determine the forces that cause increased evolutionary rates in certain genes, we analyzed alignments of 10,238 human genes to their orthologues in chimpanzee and macaque. Using a likelihood ratio test, we identified protein-coding sequences with an accelerated rate of base substitutions along the human lineage. Exons evolving at a fast rate in humans have a significant tendency to contain clusters of AT-to-GC (weak-to-strong) biased substitutions. This pattern is also observed in noncoding sequence flanking rapidly evolving exons. Accelerated exons occur in regions with elevated male recombination rates and exhibit an excess of nonsynonymous substitutions relative to the genomic average. We next analyzed genes with significantly elevated ratios of nonsynonymous to synonymous rates of base substitution (dN/dS) along the human lineage, and those with an excess of amino acid replacement substitutions relative to human polymorphism. These genes also show evidence of clusters of weak-to-strong biased substitutions. These findings indicate that a recombination-associated process, such as biased gene conversion (BGC), is driving fixation of GC alleles in the human genome. This process can lead to accelerated evolution in coding sequences and excess amino acid replacement substitutions, thereby generating significant results for tests of positive selection.


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