Differential Gene Expression in the Human Brain Is Associated with Conserved, but Not Accelerated, Noncoding Sequences

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• dc.contributor.author Meyer, Kyle A.ca
• dc.contributor.author Marquès i Bonet, Tomàs, 1975-ca
• dc.contributor.author Sestan, Nenadca
• dc.date.accessioned 2017-07-04T07:59:17Z
• dc.date.available 2017-07-04T07:59:17Z
• dc.date.issued 2017
• dc.description.abstract Previous studies have found that genes which are differentially expressed within the developing human brain disproportionately neighbor conserved noncoding sequences (CNSs) that have an elevated substitution rate in humans and in other species. One explanation for this general association of differential expression with accelerated CNSs is that genes with pre-existing patterns of differential expression have been preferentially targeted by species-specific regulatory changes. Here we provide support for an alternative explanation: genes that neighbor a greater number of CNSs have a higher probability of differential expression and a higher probability of neighboring a CNS with lineage-specific acceleration. Thus, neighboring an accelerated element from any species signals that a gene likely neighbors many CNSs. We extend the analyses beyond the prenatal time points considered in previous studies to demonstrate that this association persists across developmental and adult periods. Examining differential expression between non-neural tissues suggests that the relationship between the number of CNSs a gene neighbors and its differential expression status may be particularly strong for expression differences among brain regions. In addition, by considering this relationship, we highlight a recently defined set of putative human-specific gain-of-function sequences that, even after adjusting for the number of CNSs neighbored by genes, shows a positive relationship with upregulation in the brain compared with other tissues examined.
• dc.description.sponsorship This work was supported by the National Science Foundation Graduate Research Fellowship Program (DGE-1122492 to K.A.M); by MINECO grants BFU2014-55090-P (FEDER), BFU2015-7116-ERC, and BFU2015-6215-ERC to T.M.B; and by the National Institutes of Health (MH103339, MH110926, and MH106934 to N.S, MH106874 to T.M.B. and N.S.).
• dc.format.mimetype application/pdfca
• dc.identifier.citation Meyer KA, Marquès i Bonet T, Sestan N. Differential Gene Expression in the Human Brain Is Associated with Conserved, but Not Accelerated, Noncoding Sequences. Molecular Biology and Evolution. 2017;34(5):1217-29. DOI: 10.1093/molbev/msx076
• dc.identifier.doi http://dx.doi.org/10.1093/molbev/msx076
• dc.identifier.issn 0737-4038
• dc.identifier.uri http://hdl.handle.net/10230/32498
• dc.language.iso eng
• dc.publisher Oxford University Pressca
• dc.relation.ispartof Molecular Biology and Evolution. 2017;34(5):1217-29
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-55090
• dc.rights © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.keyword Conserved noncoding sequence
• dc.subject.keyword Gene expression
• dc.subject.keyword Brain
• dc.title Differential Gene Expression in the Human Brain Is Associated with Conserved, but Not Accelerated, Noncoding Sequencesca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion