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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372525/ https://www.ncbi.nlm.nih.gov/pubmed/22701678 http://dx.doi.org/10.1371/journal.pone.0038595 |
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author | Semeiks, Jeremy Grishin, Nick V. |
author_facet | Semeiks, Jeremy Grishin, Nick V. |
author_sort | Semeiks, Jeremy |
collection | PubMed |
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 | Online Article Text |
id | pubmed-3372525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33725252012-06-13 A Method to Find Longevity-Selected Positions in the Mammalian Proteome Semeiks, Jeremy Grishin, Nick V. PLoS One Research Article 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. Public Library of Science 2012-06-11 /pmc/articles/PMC3372525/ /pubmed/22701678 http://dx.doi.org/10.1371/journal.pone.0038595 Text en Semeiks, Grishin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Semeiks, Jeremy Grishin, Nick V. A Method to Find Longevity-Selected Positions in the Mammalian Proteome |
title | 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_short | A Method to Find Longevity-Selected Positions in the Mammalian Proteome |
title_sort | method to find longevity-selected positions in the mammalian proteome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372525/ https://www.ncbi.nlm.nih.gov/pubmed/22701678 http://dx.doi.org/10.1371/journal.pone.0038595 |
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