Substitution rate heterogeneity and the male mutation bias
Substitution rate heterogeneity and the male mutation bias
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DOI：
10.1007/s00239-005-0103-6
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发表时间：
2006-02-01
影响因子：
3.9
通讯作者：
Ellegren, H
中科院分区：
文献类型：
--
作者：
Berlin, S;Brandström, M;Ellegren, H
在许多生物体中，雄性的生殖系突变率高于雌性，这可能是精子发生中的细胞分裂比卵子发生中的细胞分裂更频繁的结果。如果大多数突变是由于DNA复制错误引起的，则男性与女性的突变率比（α（m））预计与男性和女性的生殖系细胞分裂数比（c）相似，这一假设可以通过适当估计α（m）和c进行检验。α（m）通常通过比较性染色体上的中性序列中的取代率来估计。然而，染色体间置换率的显著区域差异可能会使基于短序列置换率的α（m）估计值产生偏差。为了研究区域替换率的变化，我们估计序列的分歧，在16配子体内含子位于Z和W染色体的5种鸟类的目的鸡形目。内含子末端和潜在的保守区块被排除，以减少使用负选择序列的影响。我们发现在Z染色体内（G（15）= 37.6，p = 0.0010）以及W染色体内含子内（G（15）= 44.0，p = 0.0001）的显著替换率变化。这种异质性也影响了α（m）的估计值，在内含子之间，α（m）的估计值从1.53变化到3.51（ANOVA：F-13，F-14 =2.68，p = 0.04）。我们的研究结果表明，使用来自几个基因组区域的广泛数据集，以避免区域突变率变化的影响，并确保α（m）的准确估计的重要性。
Germline mutation rates have been found to be higher in males than in females in many organisms, a likely consequence of cell division being more frequent in spermatogenesis than in oogenesis. If the majority of mutations are due to DNA replication error, the male-to-female mutation rate ratio (alpha(m)) is expected to be similar to the ratio of the number of germ line cell divisions in males and females (c), an assumption that can be tested with proper estimates of alpha(m) and c. alpha(m) is usually estimated by comparing substitution rates in putatively neutral sequences on the sex chromosomes. However, substantial regional variation in substitution rates across chromosomes may bias estimates of alpha(m) based on the substitution rates of short sequences. To investigate regional substitution rate variation, we estimated sequence divergence in 16 gametologous introns located on the Z and W chromosomes of five bird species of the order Galliformes. Intron ends and potentially conserved blocks were excluded to reduce the effect of using sequences subject to negative selection. We found significant substitution rate variation within Z chromosome (G(15) = 37.6, p = 0.0010) as well as within W chromosome introns (G(15) = 44.0, p = 0.0001). This heterogeneity also affected the estimates of alpha(m), which varied significantly, from 1.53 to 3.51, among the introns (ANOVA: F-13,F-14 =2.68, p = 0.04). Our results suggest the importance of using extensive data sets from several genomic regions to avoid the effects of regional mutation rate variation and to ensure accurate estimates of alpha(m).