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A Phylogenetic Rate Parameter Indicates Different Sequence Divergence Patterns in Orthologs and Paralogs

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Abstract

Heterotachy—the change in sequence evolutionary rate over time—is a common feature of protein molecular evolution. Decades of studies have shed light on the conditions under which heterotachy occurs, and there is evidence that site-specific evolutionary rate shifts are correlated with changes in protein function. Here, we present a large-scale, computational analysis using thousands of protein sequence alignments from animal and plant proteomes, representing genes related either by orthology (speciation events) or paralogy (gene duplication), to compare sequence divergence patterns in orthologous vs. paralogous sequence alignments. We use sequence-based phylogenetic analyses to infer overall sequence divergence (tree length/number of sequences) and to fit site-specific rates to a discrete gamma distribution with a shape parameter α. This inference method is applied to real protein sequence alignments, as well as alignments simulated under various models of protein sequence evolution. Our simulations indicate that sequence divergence and the α parameter are positively correlated when sequences evolve with heterotachy, meaning that inferred site rate distributions appear more uniform as sequences diverge. Divergence and α are also positively correlated in both orthologous and paralogous genes, but the average increase in α (as a function of divergence) is significantly higher in paralogous protein alignments than in orthologous alignments. This result is consistent with the widely held view that recently duplicated proteins initially evolve under relaxed selective pressure, promoting functional divergence by accumulation of amino acid replacements, and hence experience more evolutionary rate fluctuations than orthologous proteins. We discuss these findings in the context of the ortholog conjecture, a long-standing assumption in molecular evolution, which posits that protein sequences related by orthology tend to be more functionally conserved than paralogous proteins.

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Acknowledgements

The authors would like to thank Dr. Claus O. Wilke and Dr. Stephanie J. Spielman for their support and assistance during the protein sequence simulation component of this study. We would also like to acknowledge the Instructional & Research Computing Center (IRCC) at Florida International University for providing HPC computing resources that have contributed to the research results reported within this paper, web: https://ircc.fiu.edu. This work was supported by a Doctoral Evidence Acquisition Fellowship (Summer 2018) and a Dissertation Year Fellowship (Fall 2018 through Spring 2019) from Florida International University.

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Correspondence to Joseph B. Ahrens or Jessica Siltberg-Liberles.

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Ahrens, J.B., Teufel, A.I. & Siltberg-Liberles, J. A Phylogenetic Rate Parameter Indicates Different Sequence Divergence Patterns in Orthologs and Paralogs. J Mol Evol 88, 720–730 (2020). https://doi.org/10.1007/s00239-020-09969-7

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