Equivocal evidence for a link between megalencephaly-related genes and primate brain size evolution

DeCasien, A, Trujillo, A, Janiak, MC ORCID: https://orcid.org/0000-0002-7759-2556, Harshaw, E, Caes, Z, Galindo, G, Petersen, R and Higham, J 2022, 'Equivocal evidence for a link between megalencephaly-related genes and primate brain size evolution' , Scientific Reports, 12 (1) .

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A large brain is a defining feature of modern humans, and much work has been dedicated to exploring the molecular underpinnings of this trait. Although numerous studies have focused on genes associated with human microcephaly, no studies have explicitly focused on genes associated with megalencephaly. Here, we investigate 16 candidate genes that have been linked to megalencephaly to determine if: (1) megalencephaly-associated genes evolved under positive selection across primates; and (2) selection pressure on megalencephaly-associated genes is linked to primate brain size. We found evidence for positive selection for only one gene, OFD1, with 1.8% of the sites estimated to have dN/dS values greater than 1; however, we did not detect a relationship between selection pressure on this gene and brain size across species, suggesting that selection for changes to non-brain size traits drove evolutionary changes to this gene. In fact, our primary analyses did not identify significant associations between selection pressure and brain size for any candidate genes. While we did detect positive associations for two genes (GPC3 and TBC1D7) when two phyletic dwarfs (i.e., species that underwent recent evolutionary decreases in brain size) were excluded, these associations did not withstand FDR correction. Overall, these results suggest that sequence alterations to megalencephaly-associated genes may have played little to no role in primate brain size evolution, possibly due to the highly pleiotropic effects of these genes. Future comparative studies of gene expression levels may provide further insights. This study enhances our understanding of the genetic underpinnings of brain size evolution in primates and identifies candidate genes that merit further exploration.

Item Type: Article
Schools: Schools > School of Computing, Science and Engineering
Schools > School of Environment and Life Sciences
Journal or Publication Title: Scientific Reports
Publisher: Nature Publishing Group UK
ISSN: 2045-2322
Funders: NSF Graduate Research Fellowship, NSF Doctoral Dissertation Research Improvement Grant, New York University MacCracken Fellowship, Natural Environment Research Council, New York University Diversity Undergraduate Research Incubator (DURI) Grant, New York University Dean’s Undergraduate Research Fund (DURF) Grant
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 29 Jul 2022 07:43
Last Modified: 17 Aug 2022 08:32
URI: https://usir.salford.ac.uk/id/eprint/64306

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