MBE Advance Access originally published online on May 2, 2007
Molecular Biology and Evolution 2007 24(8):1622-1626; doi:10.1093/molbev/msm080
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Research Articles |
Inference of Expression-Dependent Negative Selection Based on Polymorphism and Divergence in the Human Genome
Department of Biomedical Resources, National Institute of Biomedical Innovation, Osaka, Japan
E-mail: nosada{at}nibio.go.jp.
Accepted for publication April 14, 2007.
There is a mounting evidence for the correlation between the gene expression pattern and sequence divergence. However, little is known about the relationship between the gene expression pattern and polymorphism. We compiled the gene expression, polymorphism, and divergence data from the public databases of the human genome. The ratios of nonsynonymous (A) to synonymous (S) substitutions in polymorphism and divergence in the human genome were strongly influenced by the expression pattern and breadth of genes and showed strong correlations. Among the tissues we analyzed, the brain-expressed genes have the smallest and the liver-expressed genes have the largest proportion of amino acid changes both in polymorphism and divergence. The analysis implies that negative selection is the primary factor affecting expression-dependent gene evolution and the prevalent but nonuniform distribution of slightly deleterious mutations in the genome. Although the genes under relaxed negative selection evolved faster than the other genes, these genes are even more liable to slightly deleterious mutations in the population. On the other hand, nonneutral mutations in the highly conservative genes, such as brain-expressed and housekeeping genes, are largely deleterious and eliminated before they enter the population.
Key Words: gene expression • human genome • slightly deleterious mutations • natural selection • McDonald–Kreitman test
Takashi Gojobori, Associate Editor