Selection shapes the landscape of functional variation in wild house mice

Abstract Background Through human-aided dispersal over the last ~ 10,000 years, house mice (Mus musculus) have recently colonized diverse habitats across the globe, promoting the emergence of new traits that confer adaptive advantages in distinct environments. Despite their status as the premier mam...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Raman Akinyanju Lawal, Uma P. Arora, Beth L. Dumont
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Genetic diversity Mus musculus Commensalism Genetic disorder Mendelian disease Adaptation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1fa154a03aad4ba0917fffda86161afb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1fa154a03aad4ba0917fffda86161afb
record_format	dspace
spelling	oai:doaj.org-article:1fa154a03aad4ba0917fffda86161afb2021-11-21T12:42:21ZSelection shapes the landscape of functional variation in wild house mice10.1186/s12915-021-01165-31741-7007https://doaj.org/article/1fa154a03aad4ba0917fffda86161afb2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12915-021-01165-3https://doaj.org/toc/1741-7007Abstract Background Through human-aided dispersal over the last ~ 10,000 years, house mice (Mus musculus) have recently colonized diverse habitats across the globe, promoting the emergence of new traits that confer adaptive advantages in distinct environments. Despite their status as the premier mammalian model system, the impact of this demographic and selective history on the global patterning of disease-relevant trait variation in wild mouse populations is poorly understood. Results Here, we leveraged 154 whole-genome sequences from diverse wild house mouse populations to survey the geographic organization of functional variation and systematically identify signals of positive selection. We show that a significant proportion of wild mouse variation is private to single populations, including numerous predicted functional alleles. In addition, we report strong signals of positive selection at many genes associated with both complex and Mendelian diseases in humans. Notably, we detect a significant excess of selection signals at disease-associated genes relative to null expectations, pointing to the important role of adaptation in shaping the landscape of functional variation in wild mouse populations. We also uncover strong signals of selection at multiple genes involved in starch digestion, including Mgam and Amy1. We speculate that the successful emergence of the human-mouse commensalism may have been facilitated, in part, by dietary adaptations at these loci. Finally, our work uncovers multiple cryptic structural variants that manifest as putative signals of positive selection, highlighting an important and under-appreciated source of false-positive signals in genome-wide selection scans. Conclusions Overall, our findings highlight the role of adaptation in shaping wild mouse genetic variation at human disease-associated genes. Our work also highlights the biomedical relevance of wild mouse genetic diversity and underscores the potential for targeted sampling of mice from specific populations as a strategy for developing effective new mouse models of both rare and common human diseases.Raman Akinyanju LawalUma P. AroraBeth L. DumontBMCarticleGenetic diversityMus musculusCommensalismGenetic disorderMendelian diseaseAdaptationBiology (General)QH301-705.5ENBMC Biology, Vol 19, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetic diversity Mus musculus Commensalism Genetic disorder Mendelian disease Adaptation Biology (General) QH301-705.5
spellingShingle	Genetic diversity Mus musculus Commensalism Genetic disorder Mendelian disease Adaptation Biology (General) QH301-705.5 Raman Akinyanju Lawal Uma P. Arora Beth L. Dumont Selection shapes the landscape of functional variation in wild house mice
description	Abstract Background Through human-aided dispersal over the last ~ 10,000 years, house mice (Mus musculus) have recently colonized diverse habitats across the globe, promoting the emergence of new traits that confer adaptive advantages in distinct environments. Despite their status as the premier mammalian model system, the impact of this demographic and selective history on the global patterning of disease-relevant trait variation in wild mouse populations is poorly understood. Results Here, we leveraged 154 whole-genome sequences from diverse wild house mouse populations to survey the geographic organization of functional variation and systematically identify signals of positive selection. We show that a significant proportion of wild mouse variation is private to single populations, including numerous predicted functional alleles. In addition, we report strong signals of positive selection at many genes associated with both complex and Mendelian diseases in humans. Notably, we detect a significant excess of selection signals at disease-associated genes relative to null expectations, pointing to the important role of adaptation in shaping the landscape of functional variation in wild mouse populations. We also uncover strong signals of selection at multiple genes involved in starch digestion, including Mgam and Amy1. We speculate that the successful emergence of the human-mouse commensalism may have been facilitated, in part, by dietary adaptations at these loci. Finally, our work uncovers multiple cryptic structural variants that manifest as putative signals of positive selection, highlighting an important and under-appreciated source of false-positive signals in genome-wide selection scans. Conclusions Overall, our findings highlight the role of adaptation in shaping wild mouse genetic variation at human disease-associated genes. Our work also highlights the biomedical relevance of wild mouse genetic diversity and underscores the potential for targeted sampling of mice from specific populations as a strategy for developing effective new mouse models of both rare and common human diseases.
format	article
author	Raman Akinyanju Lawal Uma P. Arora Beth L. Dumont
author_facet	Raman Akinyanju Lawal Uma P. Arora Beth L. Dumont
author_sort	Raman Akinyanju Lawal
title	Selection shapes the landscape of functional variation in wild house mice
title_short	Selection shapes the landscape of functional variation in wild house mice
title_full	Selection shapes the landscape of functional variation in wild house mice
title_fullStr	Selection shapes the landscape of functional variation in wild house mice
title_full_unstemmed	Selection shapes the landscape of functional variation in wild house mice
title_sort	selection shapes the landscape of functional variation in wild house mice
publisher	BMC
publishDate	2021
url	https://doaj.org/article/1fa154a03aad4ba0917fffda86161afb
work_keys_str_mv	AT ramanakinyanjulawal selectionshapesthelandscapeoffunctionalvariationinwildhousemice AT umaparora selectionshapesthelandscapeoffunctionalvariationinwildhousemice AT bethldumont selectionshapesthelandscapeoffunctionalvariationinwildhousemice
_version_	1718418810873053184

Selection shapes the landscape of functional variation in wild house mice

Ejemplares similares