Convergent evolution of a genomic rearrangement may explain cancer resistance in hystrico- and sciuromorpha rodents

Abstract The rodents of hystricomorpha and sciuromorpha suborders exhibit remarkably lower incidence of cancer. The underlying genetic basis remains obscure. We report a convergent evolutionary split of human 3p21.31, a locus hosting a large number of tumour-suppressor genes (TSGs) and frequently de...

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Autores principales:	Yachna Jain, Keerthivasan Raanin Chandradoss, Anjoom A. V., Jui Bhattacharya, Mohan Lal, Meenakshi Bagadia, Harpreet Singh, Kuljeet Singh Sandhu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/ef48398f433c4d418e7292a983c20452
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spelling	oai:doaj.org-article:ef48398f433c4d418e7292a983c204522021-12-02T15:28:52ZConvergent evolution of a genomic rearrangement may explain cancer resistance in hystrico- and sciuromorpha rodents10.1038/s41514-021-00072-92056-3973https://doaj.org/article/ef48398f433c4d418e7292a983c204522021-09-01T00:00:00Zhttps://doi.org/10.1038/s41514-021-00072-9https://doaj.org/toc/2056-3973Abstract The rodents of hystricomorpha and sciuromorpha suborders exhibit remarkably lower incidence of cancer. The underlying genetic basis remains obscure. We report a convergent evolutionary split of human 3p21.31, a locus hosting a large number of tumour-suppressor genes (TSGs) and frequently deleted in several tumour types, in hystrico- and sciuromorphs. Analysis of 34 vertebrate genomes revealed that the synteny of 3p21.31 cluster is functionally and evolutionarily constrained in most placental mammals, but exhibit large genomic interruptions independently in hystricomorphs and sciuromorphs, owing to relaxation of underlying constraints. Hystrico- and sciuromorphs, therefore, escape from pro-tumorigenic co-deletion of several TSGs in cis. The split 3p21.31 sub-clusters gained proximity to proto-oncogene clusters from elsewhere, which might further nullify pro-tumorigenic impact of copy number variations due to co-deletion or co-amplification of genes with opposing effects. The split of 3p21.31 locus coincided with the accelerated rate of its gene expression and the body mass evolution of ancestral hystrico- and sciuromorphs. The genes near breakpoints were associated with the traits specific to hystrico- and sciuromorphs, implying adaptive significance. We conclude that the convergently evolved chromosomal interruptions of evolutionarily constrained 3p21.31 cluster might have impacted evolution of cancer resistance, body mass variation and ecological adaptations in hystrico- and sciuromorphs.Yachna JainKeerthivasan Raanin ChandradossAnjoom A. V.Jui BhattacharyaMohan LalMeenakshi BagadiaHarpreet SinghKuljeet Singh SandhuNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 7, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Yachna Jain Keerthivasan Raanin Chandradoss Anjoom A. V. Jui Bhattacharya Mohan Lal Meenakshi Bagadia Harpreet Singh Kuljeet Singh Sandhu Convergent evolution of a genomic rearrangement may explain cancer resistance in hystrico- and sciuromorpha rodents
description	Abstract The rodents of hystricomorpha and sciuromorpha suborders exhibit remarkably lower incidence of cancer. The underlying genetic basis remains obscure. We report a convergent evolutionary split of human 3p21.31, a locus hosting a large number of tumour-suppressor genes (TSGs) and frequently deleted in several tumour types, in hystrico- and sciuromorphs. Analysis of 34 vertebrate genomes revealed that the synteny of 3p21.31 cluster is functionally and evolutionarily constrained in most placental mammals, but exhibit large genomic interruptions independently in hystricomorphs and sciuromorphs, owing to relaxation of underlying constraints. Hystrico- and sciuromorphs, therefore, escape from pro-tumorigenic co-deletion of several TSGs in cis. The split 3p21.31 sub-clusters gained proximity to proto-oncogene clusters from elsewhere, which might further nullify pro-tumorigenic impact of copy number variations due to co-deletion or co-amplification of genes with opposing effects. The split of 3p21.31 locus coincided with the accelerated rate of its gene expression and the body mass evolution of ancestral hystrico- and sciuromorphs. The genes near breakpoints were associated with the traits specific to hystrico- and sciuromorphs, implying adaptive significance. We conclude that the convergently evolved chromosomal interruptions of evolutionarily constrained 3p21.31 cluster might have impacted evolution of cancer resistance, body mass variation and ecological adaptations in hystrico- and sciuromorphs.
format	article
author	Yachna Jain Keerthivasan Raanin Chandradoss Anjoom A. V. Jui Bhattacharya Mohan Lal Meenakshi Bagadia Harpreet Singh Kuljeet Singh Sandhu
author_facet	Yachna Jain Keerthivasan Raanin Chandradoss Anjoom A. V. Jui Bhattacharya Mohan Lal Meenakshi Bagadia Harpreet Singh Kuljeet Singh Sandhu
author_sort	Yachna Jain
title	Convergent evolution of a genomic rearrangement may explain cancer resistance in hystrico- and sciuromorpha rodents
title_short	Convergent evolution of a genomic rearrangement may explain cancer resistance in hystrico- and sciuromorpha rodents
title_full	Convergent evolution of a genomic rearrangement may explain cancer resistance in hystrico- and sciuromorpha rodents
title_fullStr	Convergent evolution of a genomic rearrangement may explain cancer resistance in hystrico- and sciuromorpha rodents
title_full_unstemmed	Convergent evolution of a genomic rearrangement may explain cancer resistance in hystrico- and sciuromorpha rodents
title_sort	convergent evolution of a genomic rearrangement may explain cancer resistance in hystrico- and sciuromorpha rodents
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ef48398f433c4d418e7292a983c20452
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Convergent evolution of a genomic rearrangement may explain cancer resistance in hystrico- and sciuromorpha rodents

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