Hotspots Of Biased Nucleotide Substitutions In Human Genes

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, the authors analyzed alignments of
10,238 human genes to their orthologues in chimpanzee and macaque. Using a likelihood ratio test, they 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. The authors 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.



Citation:

"Hotspots of biased nucleotide substitutions in human genes."
Berglund J, Pollard KS, Webster MT (2009)

PLoS Biol 7(1): e1000026.

doi:10.1371/journal.pbio.1000026

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