Molecular evolution of the hyaluronan synthase 2 gene in mammals : implications for adaptations to the subterranean niche and cancer resistance

Show simple item record

dc.contributor.author Faulkes, Christopher G., 1959-
dc.contributor.author Davies, Kalina T.J.
dc.contributor.author Rossiter, Stephen J.
dc.contributor.author Bennett, Nigel C., 1961-
dc.date.accessioned 2016-03-07T10:01:32Z
dc.date.issued 2015-05
dc.description.abstract The naked mole-rat (NMR) Heterocephalus glaber is a unique and fascinating mammal exhibiting many unusual adaptations to a subterranean lifestyle. The recent discovery of their resistance to cancer and exceptional longevity has opened up new and important avenues of research. Part of this resistance to cancer has been attributed to the fact that NMRs produce a modified form of hyaluronan—a key constituent of the extracellular matrix—that is thought to confer increased elasticity of the skin as an adaptation for living in narrow tunnels. This so-called high molecular mass hyaluronan (HMM-HA) stems from two apparently unique substitutions in the hyaluronan synthase 2 enzyme (HAS2). To test whether other subterranean mammals with similar selection pressures also show molecular adaptation in their HAS2 gene, we sequenced the HAS2 gene for 11 subterranean mammals and closely related species, and combined these with data from 57 other mammals. Comparative screening revealed that one of the two putatively important HAS2 substitutions in the NMR predicted to have a significant effect on hyaluronan synthase function was uniquely shared by all African mole-rats. Interestingly, we also identified multiple other amino acid substitutions in key domains of the HAS2 molecule, although the biological consequences of these for hyaluronan synthesis remain to be determined. Despite these results, we found evidence of strong purifying selection acting on the HAS2 gene across all mammals, and the NMR remains unique in its particular HAS2 sequence. Our results indicate that more work is needed to determine whether the apparent cancer resistance seen in NMR is shared by other members of the African molerat clade. en_ZA
dc.description.embargo 2016-05-31
dc.description.librarian hb2015 en_ZA
dc.description.sponsorship DST-NRF SARChI Chair for Behavioural Ecology and Physiology.European Research Council. en_ZA
dc.description.uri http://rsbl.royalsocietypublishing en_ZA
dc.identifier.citation Faulkes, CG, Davies, KTJ, Rossiter, SJ & Bennett, NC 2015, 'Molecular evolution of the hyaluronan synthase 2 gene in mammals : implications for adaptations to the subterranean niche and cancer resistance', Biology Letters, vol. 11, no. 5. en_ZA
dc.identifier.issn 1744-9561 (print)
dc.identifier.issn 1744-957X (online)
dc.identifier.other 10.1098/rsbl.2015.0185
dc.identifier.uri http://hdl.handle.net/2263/51699
dc.language.iso en en_ZA
dc.publisher The Royal Society en_ZA
dc.rights © 2015 The Author(s) Published by the Royal Society. All rights reserved. en_ZA
dc.subject Naked mole-rat (Heterocephalus glaber) en_ZA
dc.subject Hyaluronan en_ZA
dc.subject Has-2 en_ZA
dc.subject Hyaluronan synthase en_ZA
dc.subject Bathyergidae en_ZA
dc.subject Subterranean mammal en_ZA
dc.title Molecular evolution of the hyaluronan synthase 2 gene in mammals : implications for adaptations to the subterranean niche and cancer resistance en_ZA
dc.type Postprint Article en_ZA


Files in this item

This item appears in the following Collection(s)

Show simple item record