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Gene co-expression network connectivity is an important determinant of selective constraint

Hvidsten, Torgeir R. and Ingvarsson, Pär and Wang, Jing and Street, Nathaniel R. and Mähler, Niklas and Terebieniec, Barbara K. (2017). Gene co-expression network connectivity is an important determinant of selective constraint. PLoS genetics. 13, 1-33
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Abstract

While several studies have investigated general properties of the genetic architecture of natural variation in gene expression, few of these have considered natural, outbreeding populations. In parallel, systems biology has established that a general feature of biological networks is that they are scale-free, rendering them buffered against random mutations. To date, few studies have attempted to examine the relationship between the selective processes acting to maintain natural variation of gene expression and the associated co-expression network structure. Here we utilised RNA-Sequencing to assay gene expression in winter buds undergoing bud flush in a natural population of Populus tremula, an outbreeding forest tree species. We performed expression Quantitative Trait Locus (eQTL) mapping and identified 164,290 significant eQTLs associating 6,241 unique genes (eGenes) with 147,419 unique SNPs (eSNPs). We found approximately four times as many local as distant eQTLs, with local eQTLs having significantly higher effect sizes. eQTLs were primarily located in regulatory regions of genes (UTRs or flanking regions), regardless of whether they were local or distant. We used the gene expression data to infer a co-expression network and investigated the relationship between network topology, the genetic architecture of gene expression and signatures of selection. Within the co-expression network, eGenes were underrepresented in network module cores (hubs) and overrepresented in the periphery of the network, with a negative correlation between eQTL effect size and network connectivity. We additionally found that module core genes have experienced stronger selective constraint on coding and non-coding sequence, with connectivity associated with signatures of selection. Our integrated genetics and genomics results suggest that purifying selection is the primary mechanism underlying the genetic architecture of natural variation in gene expression assayed in flushing leaf buds of P. tremula and that connectivity within the co-expression network is linked to the strength of purifying selection.

Authors/Creators:Hvidsten, Torgeir R. and Ingvarsson, Pär and Wang, Jing and Street, Nathaniel R. and Mähler, Niklas and Terebieniec, Barbara K.
Title:Gene co-expression network connectivity is an important determinant of selective constraint
Series/Journal:PLoS genetics (1553-7404)
Year of publishing :2017
Volume:13
Page range:1-33
Number of Pages:33
Publisher:Public Library of Science
ISSN:1553-7404
Language:English
Publication Type:Journal article
Refereed:Yes
Article category:Scientific peer reviewed
Version:Published version
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Evolutionary Biology
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Bioinformatics and Systems Biology (methods development to be 10203)
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Genetics (medical genetics to be 30107 and agricultural genetics to be 40402)
Agrovoc terms:gene expression, genetics, Populus tremula, RNA sequence
Keywords:genetics, RNA-Sequencing, gene expression, Populus tremula
URN:NBN:urn:nbn:se:slu:epsilon-e-4439
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-4439
Additional ID:
Type of IDID
DOI10.1371/journal.pgen.1006402
Web of Science (WoS)000402549200001
ID Code:14654
Faculty:NJ - Fakulteten för naturresurser och jordbruksvetenskap
Department:(NL, NJ) > Department of Plant Biology (from 140101)
Deposited By: SLUpub Connector
Deposited On:27 Oct 2017 10:25
Metadata Last Modified:30 Oct 2017 21:50

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