Pan-mammalian analysis of molecular constraints underlying extended lifespan
Although lifespan in mammals varies over 100-fold, the precise evolutionary mechanisms underlying variation in longevity remain unknown. Species-specific genetic changes have been observed in long-lived species including the naked mole-rat, bats, and the bowhead whale, but these adaptations do not g...
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ftdoajarticles:oai:doaj.org/article:ba7dace06e084af69dc9a3c87027f940 2023-05-15T15:45:59+02:00 Pan-mammalian analysis of molecular constraints underlying extended lifespan Amanda Kowalczyk Raghavendran Partha Nathan L Clark Maria Chikina 2020-02-01T00:00:00Z https://doi.org/10.7554/eLife.51089 https://doaj.org/article/ba7dace06e084af69dc9a3c87027f940 EN eng eLife Sciences Publications Ltd https://elifesciences.org/articles/51089 https://doaj.org/toc/2050-084X doi:10.7554/eLife.51089 2050-084X e51089 https://doaj.org/article/ba7dace06e084af69dc9a3c87027f940 eLife, Vol 9 (2020) mammals evolution genomics phylogenomics longevity RERconverge Medicine R Science Q Biology (General) QH301-705.5 article 2020 ftdoajarticles https://doi.org/10.7554/eLife.51089 2022-12-30T20:56:37Z Although lifespan in mammals varies over 100-fold, the precise evolutionary mechanisms underlying variation in longevity remain unknown. Species-specific genetic changes have been observed in long-lived species including the naked mole-rat, bats, and the bowhead whale, but these adaptations do not generalize to other mammals. We present a novel method to identify associations between rates of protein evolution and continuous phenotypes across the entire mammalian phylogeny. Unlike previous analyses that focused on individual species, we treat absolute and relative longevity as quantitative traits and demonstrate that these lifespan traits affect the evolutionary constraint on hundreds of genes. Specifically, we find that genes related to cell cycle, DNA repair, cell death, the IGF1 pathway, and immunity are under increased evolutionary constraint in large and long-lived mammals. For mammals exceptionally long-lived for their body size, we find increased constraint in inflammation, DNA repair, and NFKB-related pathways. Strikingly, these pathways have considerable overlap with those that have been previously reported to have potentially adaptive changes in single-species studies, and thus would be expected to show decreased constraint in our analysis. This unexpected finding of increased constraint in many longevity-associated pathways underscores the power of our quantitative approach to detect patterns that generalize across the mammalian phylogeny. Article in Journal/Newspaper bowhead whale Directory of Open Access Journals: DOAJ Articles eLife 9 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
mammals evolution genomics phylogenomics longevity RERconverge Medicine R Science Q Biology (General) QH301-705.5 |
spellingShingle |
mammals evolution genomics phylogenomics longevity RERconverge Medicine R Science Q Biology (General) QH301-705.5 Amanda Kowalczyk Raghavendran Partha Nathan L Clark Maria Chikina Pan-mammalian analysis of molecular constraints underlying extended lifespan |
topic_facet |
mammals evolution genomics phylogenomics longevity RERconverge Medicine R Science Q Biology (General) QH301-705.5 |
description |
Although lifespan in mammals varies over 100-fold, the precise evolutionary mechanisms underlying variation in longevity remain unknown. Species-specific genetic changes have been observed in long-lived species including the naked mole-rat, bats, and the bowhead whale, but these adaptations do not generalize to other mammals. We present a novel method to identify associations between rates of protein evolution and continuous phenotypes across the entire mammalian phylogeny. Unlike previous analyses that focused on individual species, we treat absolute and relative longevity as quantitative traits and demonstrate that these lifespan traits affect the evolutionary constraint on hundreds of genes. Specifically, we find that genes related to cell cycle, DNA repair, cell death, the IGF1 pathway, and immunity are under increased evolutionary constraint in large and long-lived mammals. For mammals exceptionally long-lived for their body size, we find increased constraint in inflammation, DNA repair, and NFKB-related pathways. Strikingly, these pathways have considerable overlap with those that have been previously reported to have potentially adaptive changes in single-species studies, and thus would be expected to show decreased constraint in our analysis. This unexpected finding of increased constraint in many longevity-associated pathways underscores the power of our quantitative approach to detect patterns that generalize across the mammalian phylogeny. |
format |
Article in Journal/Newspaper |
author |
Amanda Kowalczyk Raghavendran Partha Nathan L Clark Maria Chikina |
author_facet |
Amanda Kowalczyk Raghavendran Partha Nathan L Clark Maria Chikina |
author_sort |
Amanda Kowalczyk |
title |
Pan-mammalian analysis of molecular constraints underlying extended lifespan |
title_short |
Pan-mammalian analysis of molecular constraints underlying extended lifespan |
title_full |
Pan-mammalian analysis of molecular constraints underlying extended lifespan |
title_fullStr |
Pan-mammalian analysis of molecular constraints underlying extended lifespan |
title_full_unstemmed |
Pan-mammalian analysis of molecular constraints underlying extended lifespan |
title_sort |
pan-mammalian analysis of molecular constraints underlying extended lifespan |
publisher |
eLife Sciences Publications Ltd |
publishDate |
2020 |
url |
https://doi.org/10.7554/eLife.51089 https://doaj.org/article/ba7dace06e084af69dc9a3c87027f940 |
genre |
bowhead whale |
genre_facet |
bowhead whale |
op_source |
eLife, Vol 9 (2020) |
op_relation |
https://elifesciences.org/articles/51089 https://doaj.org/toc/2050-084X doi:10.7554/eLife.51089 2050-084X e51089 https://doaj.org/article/ba7dace06e084af69dc9a3c87027f940 |
op_doi |
https://doi.org/10.7554/eLife.51089 |
container_title |
eLife |
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9 |
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1766380648831909888 |