Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland.
Mol Biol Evol. 2012 Oct;29(10):3005-22. doi: 10.1093/molbev/mss108. Epub 2012 Apr 4.
Insertions and deletions (indels) in protein-coding genes are important sources of genetic variation. Their role in creating new proteins may be especially important after gene duplication. However, little is known about how indels affect the divergence of duplicate genes. We here study thousands of duplicate genes in five fish (teleost) species with completely sequenced genomes. The ancestor of these species has been subject to a fish-specific genome duplication (FSGD) event that occurred approximately 350 Ma. We find that duplicate genes contain at least 25% more indels than single-copy genes. These indels accumulated preferentially in the first 40 my after the FSGD. A lack of widespread asymmetric indel accumulation indicates that both members of a duplicate gene pair typically experience relaxed selection. Strikingly, we observe a 30-80% excess of deletions over insertions that is consistent for indels of various lengths and across the five genomes. We also find that indels preferentially accumulate inside loop regions of protein secondary structure and in regions where amino acids are exposed to solvent. We show that duplicate genes with high indel density also show high DNA sequence divergence. Indel density, but not amino acid divergence, can explain a large proportion of the tertiary structure divergence between proteins encoded by duplicate genes. Our observations are consistent across all five fish species. Taken together, they suggest a general pattern of duplicate gene evolution in which indels are important driving forces of evolutionary change.
插入和缺失（indels）在编码蛋白的基因中是遗传变异的重要来源。在基因复制后，它们产生新蛋白质的作用可能尤为重要。然而，人们对 indels 如何影响复制基因的分化知之甚少。我们在此研究了五种鱼类（硬骨鱼）完全测序基因组中的数千个复制基因。这些物种的祖先经历了一个约 3.5 亿年前发生的鱼类特异性基因组复制（FSGD）事件。我们发现，复制基因比单拷贝基因至少多包含 25%的 indels。这些 indels 主要在前 4000 万年中积累。缺乏广泛的不对称 indel 积累表明，一个复制基因对的两个成员通常经历松弛选择。引人注目的是，我们观察到缺失比插入多 30-80%，这在各种长度的 indels 和五个基因组中都是一致的。我们还发现，indels 优先积累在蛋白质二级结构的环区和氨基酸暴露于溶剂的区域。我们表明，具有高 indel 密度的复制基因也表现出高的 DNA 序列分化。indel 密度，而不是氨基酸分化，可以解释由复制基因编码的蛋白质之间三级结构分化的很大一部分。我们的观察结果在所有五种鱼类中都是一致的。总之，它们表明复制基因进化的一般模式，其中 indels 是进化变化的重要驱动力。
