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Gene Expression Networks Across Multiple Tissues Are Associated with Rates of Molecular Evolution in Wild House Mice
Journal article   Open access   Peer reviewed

Gene Expression Networks Across Multiple Tissues Are Associated with Rates of Molecular Evolution in Wild House Mice

Katya L Mack, Megan Phifer-Rixey, Bettina Harr and Michael W Nachman
Genes, v 10(3), p225
18 Mar 2019
PMID: 30889893
url
https://doi.org/10.3390/genes10030225View
Published, Version of Record (VoR) Open

Abstract

Animals Evolution, Molecular Gene Expression Profiling - veterinary Gene Expression Regulation Gene Regulatory Networks Genomics Mice Organ Specificity Selection, Genetic Sequence Analysis, RNA - veterinary Tissue Distribution
Interactions between genes can influence how selection acts on sequence variation. In gene regulatory networks, genes that affect the expression of many other genes may be under stronger evolutionary constraint than genes whose expression affects fewer partners. While this has been studied for individual tissue types, we know less about the effects of regulatory networks on gene evolution across different tissue types. We use RNA-sequencing and genomic data collected from to construct and compare gene co-expression networks for 10 tissue types. We identify tissue-specific expression and local regulatory variation, and we associate these components of gene expression variation with sequence polymorphism and divergence. We found that genes with higher connectivity across tissues and genes associated with a greater number of cross-tissue modules showed significantly lower genetic diversity and lower rates of protein evolution. Consistent with this pattern, "hub" genes across multiple tissues also showed evidence of greater evolutionary constraint. Using allele-specific expression, we found that genes with cis-regulatory variation had lower average connectivity and higher levels of tissue specificity. Taken together, these results are consistent with strong purifying selection acting on genes with high connectivity within and across tissues.

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11 citations in Scopus

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Genetics & Heredity
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