当前位置： SCI文献检索 > MOLECULAR BIOLOGY AND EVOLUTION期刊下所有文献 > A role for selection in regulating the evolutionary emergence of disease-causing and other coding CAG repeats in humans and mice.

A role for selection in regulating the evolutionary emergence of disease-causing and other coding CAG repeats in humans and mice.

Abstract：

:The evolutionary expansion of CAG repeats in human triplet expansion disease genes is intriguing because of their deleterious phenotype. In the past, this expansion has been suggested to reflect a broad genomewide expansion of repeats, which would imply that mutational and evolutionary processes acting on repeats differ between species. Here, we tested this hypothesis by analyzing repeat- and flanking-sequence evolution in 28 repeat-containing genes that had been sequenced in humans and mice and by considering overall lengths and distributions of CAG repeats in the two species. We found no evidence that these repeats were longer in humans than in mice. We also found no evidence for preferential accumulation of CAG repeats in the human genome relative to mice from an analysis of the lengths of repeats identified in sequence databases. We then investigated whether sequence properties, such as base and amino acid composition and base substitution rates, showed any relationship to repeat evolution. We found that repeat-containing genes were enriched in certain amino acids, presumably as the result of selection, but that this did not reflect underlying biases in base composition. We also found that regions near repeats showed higher nonsynonymous substitution rates than the remainder of the gene and lower nonsynonymous rates in genes that contained a repeat in both the human and the mouse. Higher rates of nonsynonymous mutation in the neighborhood of repeats presumably reflect weaker purifying selection acting in these regions of the proteins, while the very low rate of nonsynonymous mutation in proteins containing a CAG repeat in both species presumably reflects a high level of purifying selection. Based on these observations, we propose that the mutational processes giving rise to polyglutamine repeats in human and murine proteins do not differ. Instead, we propose that the evolution of polyglutamine repeats in proteins results from an interplay between mutational processes and selection.

journal_name

Mol Biol Evol

journal_title

Molecular biology and evolution

authors

Hancock JM,Worthey EA,Santibáñez-Koref MF

doi

10.1093/oxfordjournals.molbev.a003873

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

1014-23

issue

eissn

0737-4038

issn

1537-1719

journal_volume

pub_type

杂志文章

在线工具

A role for selection in regulating the evolutionary emergence of disease-causing and other coding CAG repeats in humans and mice.