High mutation rate and predominance of insertions in the Caenorhabditis elegans nuclear genome
High mutation rate and predominance of insertions in the Caenorhabditis elegans nuclear genome
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DOI：
10.1038/nature02697
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发表时间：
2004-08-05
期刊：
影响因子：
64.8
通讯作者：
Thomas, WK
中科院分区：
文献类型：
--
作者：
Denver, DR;Morris, K;Thomas, WK
突变在遗传疾病的发病中起着关键作用，是进化的基本基础。然而，目前对自发突变率和谱的估计来自间接和有偏差的测量。例如，秀丽隐杆线虫的突变率估计是根据对几个具有可见表型的遗传位点的观察推断出来的，并且在一个数量级上有所不同(1)。哺乳动物的替代方法，依赖于假基因位点(2)和四重退化密码子位置(3)的系统发育比较，在比较物种的实际代数上存在不确定性，并且无法排除与自然选择相关的偏差。在这里，我们提供了一组秀丽隐杆线虫突变积累线的核突变率及其分子谱的直接和无偏估计，显示突变率比以前的间接估计高约十倍，并且插入多于缺失。由于缺失在秀丽隐杆线虫的假基因变异模式中占主导地位（4,5），我们的观察结果表明，自然选择可能在促进小基因组大小方面发挥重要作用，并挑战了假基因分化准确反映自发突变谱的普遍假设。
Mutations have pivotal functions in the onset of genetic diseases and are the fundamental substrate for evolution. However, present estimates of the spontaneous mutation rate and spectrum are derived from indirect and biased measurements. For instance, mutation rate estimates for Caenorhabditis elegans are extrapolated from observations on a few genetic loci with visible phenotypes and vary over an order of magnitude(1). Alternative approaches in mammals, relying on phylogenetic comparisons of pseudogene loci(2) and fourfold degenerate codon positions(3), suffer from uncertainties in the actual number of generations separating the compared species and the inability to exclude biases associated with natural selection. Here we provide a direct and unbiased estimate of the nuclear mutation rate and its molecular spectrum with a set of C. elegans mutation-accumulation lines that reveal a mutation rate about tenfold higher than previous indirect estimates and an excess of insertions over deletions. Because deletions dominate patterns of C. elegans pseudogene variation(4,5), our observations indicate that natural selection might be significant in promoting small genome size, and challenge the prevalent assumption that pseudogene divergence accurately reflects the spontaneous mutation spectrum.