Purifying selection maintains highly conserved Noncoding sequences in Drosophila
Purifying selection maintains highly conserved Noncoding sequences in Drosophila
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DOI：
10.1093/molbev/msm150
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发表时间：
2007-10-01
影响因子：
10.7
通讯作者：
Bergman, Casey M.
中科院分区：
文献类型：
--
作者：
Casillas, Sonia;Barbadilla, Antonio;Bergman, Casey M.
大多数后生动物基因组由非蛋白质编码区组成，尽管大多数非编码DNA序列的功能意义仍然未知。高度保守的非编码序列（CNSs）已被证明是功能受限序列如顺式调控元件和非编码RNA基因的可靠指标。然而，CNSs可能来自非选择性的进化过程，例如具有极低突变率的基因组区域，称为突变“冷点”。“在这里，我们结合联合收割机比较基因组数据，从最近完成的昆虫基因组计划与人口遗传数据在黑腹果蝇，以测试预测的突变冷点模型的中枢神经系统进化的果蝇属。我们发现，内含子和基因间CNSs的点突变表现出显着减少的水平相对于多态性水平的分歧，以及一个显着过量的罕见的衍生等位基因，与CNSs之间的非保守间隔区或编码区中的4倍沉默位点相比。控制净化选择的影响，我们没有发现积极的选择作用于果蝇CNSs的证据，虽然我们确实发现证据的行动，经常性的积极选择CNSs之间的间隔区。我们估计，在果蝇的CNSs的网站约85%的限制与选择系数（N（e）s）的顺序为10-100，因此，估计的强度和纯化选择下的网站的数量是更大的果蝇CNSs相对于那些在人类基因组。这些模式的非中性分子进化是不相容的突变冷点假说来解释存在的CNSs在果蝇，再加上类似的发现在哺乳动物中，反对一般的可能性，CNSs产生突变冷点在任何后生动物基因组。
The majority of metazoan genomes consist of nonprotein-coding regions, although the functional significance of most noncoding DNA sequences remains unknown. Highly conserved noncoding sequences (CNSs) have proven to be reliable indicators of functionally constrained sequences such as cis-regulatory elements and noncoding RNA genes. However, CNSs may arise from nonselective evolutionary processes such as genomic regions with extremely low mutation rates known as mutation "cold spots." Here we combine comparative genomic data from recently completed insect genome projects with population genetic data in Drosophila melanogaster to test predictions of the mutational cold spot model of CNS evolution in the genus Drosophila. We find that point mutations in intronic and intergenic CNSs exhibit a significant reduction in levels of divergence relative to levels of polymorphism, as well as a significant excess of rare derived alleles, compared with either the nonconserved spacer regions between CNSs or with 4-fold silent sites in coding regions. Controlling for the effects of purifying selection, we find no evidence of positive selection acting on Drosophila CNSs, although we do find evidence for the action of recurrent positive selection in the spacer regions between CNSs. We estimate that similar to 85% of sites in Drosophila CNSs are under constraint with selection coefficients (N(e)s) on the order of 10-100, and thus, the estimated strength and number of sites under purifying selection is greater for Drosophila CNSs relative to those in the human genome. These patterns of nonneutral molecular evolution are incompatible with the mutational cold spot hypothesis to explain the existence of CNSs in Drosophila and, coupled with similar findings in mammals, argue against the general likelihood that CNSs are generated by mutational cold spots in any metazoan genome.