State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao, 266237, China.
Physical Examination Office of Shandong Province, Health and Family Planning Commission of Shandong Province, Jinan, 250014, China.
BMC Genomics. 2018 Oct 24;19(1):771. doi: 10.1186/s12864-018-5178-8.
Quantitative evaluation of protein structural evolution is important for our understanding of protein biological functions and their evolutionary adaptation, and is useful in guiding protein engineering. However, compared to the models for sequence evolution, the quantitative models for protein structural evolution received less attention. Ancient protein superfamilies are often considered versatile, allowing genetic and functional diversifications during long-term evolution. In this study, we investigated the quantitative impacts of sequence variations on the structural evolution of homologues in 68 ancient protein superfamilies that exist widely in sequenced eukaryotic, bacterial and archaeal genomes.
We found that the accumulated structural variations within ancient superfamilies could be explained largely by a bilinear model that simultaneously considers amino acid substitution and insertion/deletion (indel). Both substitutions and indels are essential for explaining the structural variations within ancient superfamilies. For those ancient superfamilies with high bilinear multiple correlation coefficients, the influence of each unit of substitution or indel on structural variations is almost constant within each superfamily, but varies greatly among different superfamilies. The influence of each unit indel on structural variations is always larger than that of each unit substitution within each superfamily, but the accumulated contributions of indels to structural variations are lower than those of substitutions in most superfamilies. The total contributions of sequence indels and substitutions (46% and 54%, respectively) to the structural variations that result from sequence variations are slightly different in ancient superfamilies.
Structural variations within ancient protein superfamilies accumulated under the significantly bilinear influence of amino acid substitutions and indels in sequences. Both substitutions and indels are essential for explaining the structural variations within ancient superfamilies. For those structural variations resulting from sequence variations, the total contribution of indels is slightly lower than that of amino acid substitutions. The regular clock exists not only in protein sequences, but also probably in protein structures.
定量评估蛋白质结构进化对于理解蛋白质的生物功能及其进化适应非常重要，并且有助于指导蛋白质工程。然而，与序列进化模型相比，蛋白质结构进化的定量模型受到的关注较少。古老的蛋白质超家族通常被认为是多功能的，允许在长期进化过程中进行遗传和功能多样化。在这项研究中，我们调查了序列变异对存在于已测序真核生物、细菌和古菌基因组中的 68 个古老蛋白质超家族同源物结构进化的定量影响。
我们发现，古老超家族内积累的结构变异可以用一个同时考虑氨基酸替换和插入/缺失（indel）的双线性模型来很好地解释。替换和 indel 对于解释古老超家族内的结构变异都是必不可少的。对于那些具有高双线性多重相关系数的古老超家族，每个替换或 indel 单位对结构变异的影响在每个超家族内几乎是恒定的，但在不同的超家族之间变化很大。每个 indel 单位对结构变异的影响在每个超家族内总是大于每个替换单位的影响，但 indel 对结构变异的累积贡献在大多数超家族中低于替换的贡献。序列 indel 和替换（分别为 46%和 54%）对序列变异引起的结构变异的总贡献在古老超家族中略有不同。
古老蛋白质超家族内的结构变异是在序列中氨基酸替换和 indel 的显著双线性影响下积累的。替换和 indel 对于解释古老超家族内的结构变异都是必不可少的。对于那些由序列变异引起的结构变异，indel 的总贡献略低于氨基酸替换。时钟不仅存在于蛋白质序列中，也可能存在于蛋白质结构中。
