title: Insight into role of selection in the evolution of polyglutamine tracts in humans.
abstract: Glutamine tandem repeats are common in eukaryotic proteins. Although some studies have proposed that replication slippage plays an important role in shaping these repeats, the role of natural selection in glutamine tandem repeat evolution is somewhat unclear. In this study, we identified all of the glutamine tandem repeats containing four or more glutamines in human proteins and then estimated the nonsynonymous (d(N)) and synonymous (d(S)) substitution rates for the regions flanking the glutamine tandem repeats and the proteins containing them. The results indicated that most of the proteins containing polyglutamine (polyQ) tracts of four or more glutamines have undergone purifying selection, and that the purifying selection for the regions flanking the repeats is weaker. Additionally, we observed that the conserved repeats were under stronger selection constraints than the nonconserved repeats. Interestingly, we found that there was a higher level of purifying selection for the regions flanking the polyQ tracts encoded by pure CAG codons compared with those encoded by mixed codons. Based on our findings, we propose that selection has played a more important role than was previously speculated in constraining the expansion of polyQ tracts encoded by pure codons.
authors: College of Veterinary Medicine, China Agricultural University, Beijing, China. lhwcau@163.com
authors: Hongwei
authors: H
authors: Li
authors: Jing
authors: J
authors: Liu
authors: Keliang
authors: K
authors: Wu
authors: Yuan
authors: Y
authors: Chen
mesh_terms: D000818:Animals; D003062:Codon / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D010455:Peptides / Q000235:genetics*; D051381:Rats; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics*; D020539:Sequence Analysis, Protein / Q000379:methods*
chemical_list: D003062:Codon; D010455:Peptides; C097188:polyglutamine