Rodin Sergei N, Parkhomchuk Dmitri V, Rodin Andrei S, Holmquist Gerald P, Riggs Arthur D
Theoretical Biology Department, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
DNA Cell Biol. 2005 Sep;24(9):529-42. doi: 10.1089/dna.2005.24.529.
Gene duplication is the main source of evolutionary novelties. However, the problem with duplicates is that the purifying selection overlooks deleterious mutations in the redundant sequence, which therefore, instead of gaining a new function, often degrades into a functionless pseudogene. This risk of functional loss instead of gain is much higher for small populations of higher organisms with a slow and complex development. We propose that it is the epigenetic tissue/stage-complementary silencing of duplicates that makes them exposable to the purifying selection, thus saving them from pseudogenization and opening the way towards new function(s). Our genome-wide analyses of gene duplicates in several eukaryotic species combined with the phylogenetic comparison of vertebrate alpha- and beta-globin gene clusters strongly support this epigenetic complementation (EC) model. The distinctive condition for a new duplicate to survive by the EC mechanism seems to be its repositioning to an ectopic site, which is accompanied by changes in the rate and direction of mutagenesis. The most distinguished in this respect is the human genome. In this review, we extend and discuss the data on the EC- and repositioning-dependent fate of gene duplicates with the special emphasis on the problem of detecting brief postduplication period of adaptive evolution driven by positive selection. Accordingly, we propose a new CpG-focused measure of selection that is insensitive to translocation-caused biases in mutagenesis.
基因复制是进化新特性的主要来源。然而，复制基因存在的问题是，纯化选择会忽略冗余序列中的有害突变，因此，复制基因往往不会获得新功能，反而常常退化为无功能的假基因。对于发育缓慢且复杂的高等生物的小群体而言，功能丧失而非获得的这种风险要高得多。我们提出，正是复制基因的表观遗传组织/阶段互补性沉默使其能够接受纯化选择，从而使其免于假基因化，并为新功能的产生开辟道路。我们对几种真核生物物种中的基因复制进行的全基因组分析，结合脊椎动物α-和β-珠蛋白基因簇的系统发育比较，有力地支持了这种表观遗传互补（EC）模型。新的复制基因通过EC机制存活的独特条件似乎是其重新定位到一个异位位点，这伴随着诱变率和诱变方向的变化。在这方面最突出的是人类基因组。在本综述中，我们扩展并讨论了关于基因复制的EC和重新定位依赖性命运的数据，特别强调了检测由正选择驱动的适应性进化的短暂复制后时期这一问题。因此，我们提出了一种新的以CpG为重点的选择度量方法，该方法对诱变中易位引起的偏差不敏感。
