Convergent and parallel evolution provide unique insights into the mechanisms of natural selection. Some of the most striking convergent and parallel (collectively recurrent) amino acid substitutions in proteins are adaptive, but there are also many that are selectively neutral. Accordingly, genome-wide assessment has shown that recurrent sequence evolution in orthologs is chiefly explained by nearly neutral evolution. For paralogs, more frequent functional change is expected because additional copies are generally not retained if they do not acquire their own niche. Yet, it is unknown to what extent recurrent sequence differentiation is discernible after independent gene duplications in different eukaryotic taxa. We develop a framework that detects patterns of recurrent sequence evolution in duplicated genes. This is used to analyze the genomes of 90 diverse eukaryotes. We find a remarkable number of families with a potentially predictable functional differentiation following gene duplication. In some protein families, more than ten independent duplications show a similar sequence-level differentiation between paralogs. Based on further analysis, the sequence divergence is found to be generally asymmetric. Moreover, about 6% of the recurrent sequence evolution between paralog pairs can be attributed to recurrent differentiation of subcellular localization. Finally, we reveal the specific recurrent patterns for the gene families Hint1/Hint2, Sco1/Sco2 and vma11/vma3. The presented methodology provides a means to study the biochemical underpinning of functional differentiation between paralogs. For instance, two abundantly repeated substitutions are identified between independently derived Sco1 and Sco2 paralogs. Such identified substitutions allow direct experimental testing of the biological role of these residues for the repeated functional differentiation. We also uncover a diverse set of families with recurrent sequence evolution and reveal trends in the functional and evolutionary trajectories of this hitherto understudied phenomenon.

中文翻译：

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独立基因复制后的循环序列进化。

融合和并行进化提供了对自然选择机制的独特见解。蛋白质中一些最引人注目的收敛和平行（统称为循环）氨基酸取代具有适应性，但也有许多是选择性中性的。因此，全基因组评估表明直系同源物中的重复序列进化主要由近乎中性的进化解释。对于旁系同源物，预计会发生更频繁的功能更改，因为如果它们没有获得自己的位置，通常不会保留其他副本。然而，在不同的真核生物类群中进行独立的基因复制后，在何种程度上可辨别递归序列的分化尚不清楚。我们开发了一个框架，可检测重复基因中重复序列进化的模式。这用于分析90种不同的真核生物的基因组。我们发现大量的基因复制后具有潜在可预测的功能分化的家庭。在某些蛋白质家族中，十个以上的独立重复序列在旁系同源物之间显示出相似的序列水平差异。根据进一步的分析，发现序列分歧通常是不对称的。而且，旁系同源物对之间约6％的循环序列进化可归因于亚细胞定位的反复分化。最后，我们揭示了基因家族Hint1 / Hint2，Sco1 / Sco2和vma11 / vma3的特定复发模式。提出的方法学提供了一种手段来研究旁系同源物之间的功能分化的生化基础。例如，在独立衍生的Sco1和Sco2旁系同源物之间鉴定了两个重复重复的位置。通过这种鉴定的取代，可以对这些残基的生物学作用进行直接的实验测试，以进行重复的功能区分。我们还发现了一系列具有递归序列进化的家族，并揭示了这一迄今未被研究的现象在功能和进化轨迹上的趋势。