Positive Selection in Gene Regulatory Factors Suggests Adaptive Pleiotropic Changes During Human Evolution.

Autor:	Jovanovic VM; Human Biology and Primate Evolution, Freie Universität Berlin, Berlin, Germany.; Bioinformatics Solution Center, Freie Universität Berlin, Berlin, Germany., Sarfert M; Human Biology and Primate Evolution, Freie Universität Berlin, Berlin, Germany., Reyna-Blanco CS; Department of Biology, University of Fribourg, Fribourg, Switzerland.; Swiss Institute of Bioinformatics, Fribourg, Switzerland., Indrischek H; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.; Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.; Center for Systems Biology Dresden, Dresden, Germany., Valdivia DI; Evolutionary Genomics Laboratory and Genome Topology and Regulation Laboratory, Genetic Engineering Department, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-Irapuato), Irapuato, Mexico., Shelest E; Centre for Enzyme Innovation, University of Portsmouth, Portsmouth, United Kingdom., Nowick K; Human Biology and Primate Evolution, Freie Universität Berlin, Berlin, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2021 May 17; Vol. 12, pp. 662239. Date of Electronic Publication: 2021 May 17 (Print Publication: 2021).
DOI:	10.3389/fgene.2021.662239
Abstrakt:	Gene regulatory factors (GRFs), such as transcription factors, co-factors and histone-modifying enzymes, play many important roles in modifying gene expression in biological processes. They have also been proposed to underlie speciation and adaptation. To investigate potential contributions of GRFs to primate evolution, we analyzed GRF genes in 27 publicly available primate genomes. Genes coding for zinc finger (ZNF) proteins, especially ZNFs with a Krüppel-associated box (KRAB) domain were the most abundant TFs in all genomes. Gene numbers per TF family differed between all species. To detect signs of positive selection in GRF genes we investigated more than 3,000 human GRFs with their more than 70,000 orthologs in 26 non-human primates. We implemented two independent tests for positive selection, the branch-site-model of the PAML suite and aBSREL of the HyPhy suite, focusing on the human and great ape branch. Our workflow included rigorous procedures to reduce the number of false positives: excluding distantly similar orthologs, manual corrections of alignments, and considering only genes and sites detected by both tests for positive selection. Furthermore, we verified the candidate sites for selection by investigating their variation within human and non-human great ape population data. In order to approximately assign a date to positively selected sites in the human lineage, we analyzed archaic human genomes. Our work revealed with high confidence five GRFs that have been positively selected on the human lineage and one GRF that has been positively selected on the great ape lineage. These GRFs are scattered on different chromosomes and have been previously linked to diverse functions. For some of them a role in speciation and/or adaptation can be proposed based on the expression pattern or association with human diseases, but it seems that they all contributed independently to human evolution. Four of the positively selected GRFs are KRAB-ZNF proteins, that induce changes in target genes co-expression and/or through arms race with transposable elements. Since each positively selected GRF contains several sites with evidence for positive selection, we suggest that these GRFs participated pleiotropically to phenotypic adaptations in humans. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Jovanovic, Sarfert, Reyna-Blanco, Indrischek, Valdivia, Shelest and Nowick.)
Databáze:	MEDLINE
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