Ancestral sequence reconstruction has had recent success in decoding the origins and the determinants of complex protein functions. However, phylogenetic analyses of remote homologues must handle extreme amino acid sequence diversity resulting from extended periods of evolutionary change. We exploited the wealth of protein structures to develop an evolutionary model based on protein secondary structure. The approach follows the differences between discrete secondary structure states observed in modern proteins and those hypothesized in their immediate ancestors. We implemented maximum likelihood‐based phylogenetic inference to reconstruct ancestral secondary structure. The predictive accuracy from the use of the evolutionary model surpasses that of comparative modeling and sequence‐based prediction; the reconstruction extracts information not available from modern structures or the ancestral sequences alone. Based on a phylogenetic analysis of a sequence‐diverse protein family, we showed that the model can highlight relationships that are evolutionarily rooted in structure and not evident in amino acid‐based analysis.

中文翻译：

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蛋白质二级结构的进化模型能够揭示新的生物学关系。

祖先序列重建最近在解码复杂蛋白质功能的起源和决定因素方面取得了成功。但是，远程同源物的系统进化分析必须处理由于进化变化的延长而导致的极端氨基酸序列多样性。我们利用丰富的蛋白质结构来开发基于蛋白质二级结构的进化模型。该方法遵循了在现代蛋白质中观察到的离散二级结构状态与在其直接祖先中假设的状态之间的差异。我们实施了基于最大似然的系统发育推断来重建祖先的二级结构。使用进化模型的预测准确性超过比较建模和基于序列的预测；重建过程仅从现代结构或祖先序列中提取不到的信息。基于序列多样化蛋白质家族的系统发育分析，我们表明该模型可以突出显示进化上扎根于结构且在基于氨基酸的分析中不明显的关系。