State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China.
Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1187-92. doi: 10.1073/pnas.1109047109. Epub 2012 Jan 9.
Gene duplication plays key roles in organismal evolution. Duplicate genes, if they survive, tend to diverge in regulatory and coding regions. Divergences in coding regions, especially those that can change the function of the gene, can be caused by amino acid-altering substitutions and/or alterations in exon-intron structure. Much has been learned about the mode, tempo, and consequences of nucleotide substitutions, yet relatively little is known about structural divergences. In this study, by analyzing 612 pairs of sibling paralogs from seven representative gene families and 300 pairs of one-to-one orthologs from different species, we investigated the occurrence and relative importance of structural divergences during the evolution of duplicate and nonduplicate genes. We found that structural divergences have been very prevalent in duplicate genes and, in many cases, have led to the generation of functionally distinct paralogs. Comparisons of the genomic sequences of these genes further indicated that the differences in exon-intron structure were actually accomplished by three main types of mechanisms (exon/intron gain/loss, exonization/pseudoexonization, and insertion/deletion), each of which contributed differently to structural divergence. Like nucleotide substitutions, insertion/deletion and exonization/pseudoexonization occurred more or less randomly, with the number of observable mutational events per gene pair being largely proportional to evolutionary time. Notably, however, compared with paralogs with similar evolutionary times, orthologs have accumulated significantly fewer structural changes, whereas the amounts of amino acid replacements accumulated did not show clear differences. This finding suggests that structural divergences have played a more important role during the evolution of duplicate than nonduplicate genes.
基因复制在生物进化中起着关键作用。如果复制基因存活下来，它们往往会在调控和编码区域发生分化。编码区域的分化，尤其是那些能够改变基因功能的分化，可能是由氨基酸改变的替换和/或外显子-内含子结构的改变引起的。人们已经了解了核苷酸替换的模式、速度和后果，但相对而言，结构分化的情况知之甚少。在这项研究中，我们通过分析来自七个代表性基因家族的 612 对兄弟姐妹旁系同源物和来自不同物种的 300 对一对一的直系同源物，研究了在重复和非重复基因进化过程中结构分化的发生和相对重要性。我们发现结构分化在重复基因中非常普遍，并且在许多情况下导致了功能不同的旁系同源物的产生。对这些基因的基因组序列进行比较进一步表明，外显子-内含子结构的差异实际上是通过三种主要机制（外显子/内含子获得/缺失、外显子化/假外显子化和插入/缺失）实现的，每种机制对外显子-内含子结构的分化都有不同的贡献。与核苷酸替换一样，插入/缺失和外显子化/假外显子化或多或少地随机发生，每个基因对中可观察到的突变事件数量与进化时间大致成正比。值得注意的是，然而，与具有相似进化时间的旁系同源物相比，直系同源物积累的结构变化明显较少，而积累的氨基酸替换数量没有明显差异。这一发现表明，结构分化在重复基因而非非重复基因的进化中发挥了更重要的作用。
