The scale of mutational variation in the murid genome
The scale of mutational variation in the murid genome
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DOI：
10.1101/gr.3895005
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发表时间：
2005-08-01
期刊：
影响因子：
7
通讯作者：
Keightley, PD
中科院分区：
文献类型：
--
作者：
Gaffney, DJ;Keightley, PD
突变率在哺乳动物基因组中各不相同，但人们对这种变化发生的规模知之甚少。了解突变变异的幅度和规模是理解驱动突变的过程所必需的，并且对于为比较基因组学研究制定稳健的零假设至关重要。在这里，我们估计突变变异的规模在murid基因组中，通过计算空间自相关的核苷酸取代率在祖先的重复。这种转座因子是中性进化序列的良好候选者，因此非常适合于突变率变异的研究。我们发现，自相关系数衰减到一个接近于零的值，类似于15 Mb，在100 kb以下的突变率几乎没有明显的变化。我们的结论是，主要规模超过突变率的变化是亚染色体。此外，我们的分析表明，染色体内的突变变异超过变异之间，染色体约一个数量级。因此，同一染色体不同区域之间的突变率差异经常超过整个常染色体之间以及常染色体与X染色体之间的差异。我们的研究结果表明，在男性生殖系中花费的时间以外的因素在驱动突变率方面也很重要。这引发了关于产生新突变的生物学机制的问题，并对男性驱动的进化研究产生了影响。
Mutation rates vary across mammalian genomes, but little is known about the scale over which this variation occurs. Knowledge of the magnitude and scale of mutational variation is required to understand the processes that drive mutation, and is essential in formulating a robust null hypothesis for comparative genomics studies. Here we estimate the scale of mutational variation in the murid genome by calculating the spatial autocorrelation of nucleotide substitution rates in ancestral repeats. Such transposable elements are good candidates for neutrally evolving sequence and therefore well suited for the study of mutation rate variation. We find that the autocorrelation coefficient decays to a value close to zero by similar to 15 Mb, with little apparent variation in mutation rate under 100 kb. We conclude that the primary scale over which mutation rates vary is subchromosomal. Furthermore, our analysis shows that within-chromosome mutational variability exceeds variation among, chromosomes by approximately one order of magnitude. Thus, differences in mutation rate between different regions of the same chromosome frequently exceed differences both between whole autosomes and between autosomes and the X-chromosome. Our results indicate that factors other than the time spent in the male germ line are important in driving mutation rates. This raises questions about the biological mechanism(s) that produce new mutations and has implications for the study of male-driven evolution.