A method to find longevity-selected positions in the mammalian proteome.

Evolutionary theory suggests that the force of natural selection decreases with age. To explore the extent to which this prediction directly affects protein structure and function, we used multiple regression to find longevity-selected positions, defined as the columns of a sequence alignment conser...

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Autores principales:	Jeremy Semeiks, Nick V Grishin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4e6cd535603f43648b33404c83b745a7
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id	oai:doaj.org-article:4e6cd535603f43648b33404c83b745a7
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spelling	oai:doaj.org-article:4e6cd535603f43648b33404c83b745a72021-11-18T07:15:51ZA method to find longevity-selected positions in the mammalian proteome.1932-620310.1371/journal.pone.0038595https://doaj.org/article/4e6cd535603f43648b33404c83b745a72012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22701678/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Evolutionary theory suggests that the force of natural selection decreases with age. To explore the extent to which this prediction directly affects protein structure and function, we used multiple regression to find longevity-selected positions, defined as the columns of a sequence alignment conserved in long-lived but not short-lived mammal species. We analyzed 7,590 orthologous protein families in 33 mammalian species, accounting for body mass, phylogeny, and species-specific mutation rate. Overall, we found that the number of longevity-selected positions in the mammalian proteome is much higher than would be expected by chance. Further, these positions are enriched in domains of several proteins that interact with one another in inflammation and other aging-related processes, as well as in organismal development. We present as an example the kinase domain of anti-müllerian hormone type-2 receptor (AMHR2). AMHR2 inhibits ovarian follicle recruitment and growth, and a homology model of the kinase domain shows that its longevity-selected positions cluster near a SNP associated with delayed human menopause. Distinct from its canonical role in development, this region of AMHR2 may function to regulate the protein's activity in a lifespan-specific manner.Jeremy SemeiksNick V GrishinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e38595 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeremy Semeiks Nick V Grishin A method to find longevity-selected positions in the mammalian proteome.
description	Evolutionary theory suggests that the force of natural selection decreases with age. To explore the extent to which this prediction directly affects protein structure and function, we used multiple regression to find longevity-selected positions, defined as the columns of a sequence alignment conserved in long-lived but not short-lived mammal species. We analyzed 7,590 orthologous protein families in 33 mammalian species, accounting for body mass, phylogeny, and species-specific mutation rate. Overall, we found that the number of longevity-selected positions in the mammalian proteome is much higher than would be expected by chance. Further, these positions are enriched in domains of several proteins that interact with one another in inflammation and other aging-related processes, as well as in organismal development. We present as an example the kinase domain of anti-müllerian hormone type-2 receptor (AMHR2). AMHR2 inhibits ovarian follicle recruitment and growth, and a homology model of the kinase domain shows that its longevity-selected positions cluster near a SNP associated with delayed human menopause. Distinct from its canonical role in development, this region of AMHR2 may function to regulate the protein's activity in a lifespan-specific manner.
format	article
author	Jeremy Semeiks Nick V Grishin
author_facet	Jeremy Semeiks Nick V Grishin
author_sort	Jeremy Semeiks
title	A method to find longevity-selected positions in the mammalian proteome.
title_short	A method to find longevity-selected positions in the mammalian proteome.
title_full	A method to find longevity-selected positions in the mammalian proteome.
title_fullStr	A method to find longevity-selected positions in the mammalian proteome.
title_full_unstemmed	A method to find longevity-selected positions in the mammalian proteome.
title_sort	method to find longevity-selected positions in the mammalian proteome.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/4e6cd535603f43648b33404c83b745a7
work_keys_str_mv	AT jeremysemeiks amethodtofindlongevityselectedpositionsinthemammalianproteome AT nickvgrishin amethodtofindlongevityselectedpositionsinthemammalianproteome AT jeremysemeiks methodtofindlongevityselectedpositionsinthemammalianproteome AT nickvgrishin methodtofindlongevityselectedpositionsinthemammalianproteome
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A method to find longevity-selected positions in the mammalian proteome.

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