Larger mammalian body size leads to lower retroviral activity.

Retroviruses have been infecting mammals for at least 100 million years, leaving descendants in host genomes known as endogenous retroviruses (ERVs). The abundance of ERVs is partly determined by their mode of replication, but it has also been suggested that host life history traits could enhance or...

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Main Authors: Aris Katzourakis, Gkikas Magiorkinis, Aaron G Lim, Sunetra Gupta, Robert Belshaw, Robert Gifford
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-07-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1004214
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author Aris Katzourakis
Gkikas Magiorkinis
Aaron G Lim
Sunetra Gupta
Robert Belshaw
Robert Gifford
author_facet Aris Katzourakis
Gkikas Magiorkinis
Aaron G Lim
Sunetra Gupta
Robert Belshaw
Robert Gifford
author_sort Aris Katzourakis
collection DOAJ
description Retroviruses have been infecting mammals for at least 100 million years, leaving descendants in host genomes known as endogenous retroviruses (ERVs). The abundance of ERVs is partly determined by their mode of replication, but it has also been suggested that host life history traits could enhance or suppress their activity. We show that larger bodied species have lower levels of ERV activity by reconstructing the rate of ERV integration across 38 mammalian species. Body size explains 37% of the variance in ERV integration rate over the last 10 million years, controlling for the effect of confounding due to other life history traits. Furthermore, 68% of the variance in the mean age of ERVs per genome can also be explained by body size. These results indicate that body size limits the number of recently replicating ERVs due to their detrimental effects on their host. To comprehend the possible mechanistic links between body size and ERV integration we built a mathematical model, which shows that ERV abundance is favored by lower body size and higher horizontal transmission rates. We argue that because retroviral integration is tumorigenic, the negative correlation between body size and ERV numbers results from the necessity to reduce the risk of cancer, under the assumption that this risk scales positively with body size. Our model also fits the empirical observation that the lifetime risk of cancer is relatively invariant among mammals regardless of their body size, known as Peto's paradox, and indicates that larger bodied mammals may have evolved mechanisms to limit ERV activity.
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spelling doaj-art-fadc593f75324e04a9ff40dc68e6946c2025-08-20T02:34:10ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-07-01107e100421410.1371/journal.ppat.1004214Larger mammalian body size leads to lower retroviral activity.Aris KatzourakisGkikas MagiorkinisAaron G LimSunetra GuptaRobert BelshawRobert GiffordRetroviruses have been infecting mammals for at least 100 million years, leaving descendants in host genomes known as endogenous retroviruses (ERVs). The abundance of ERVs is partly determined by their mode of replication, but it has also been suggested that host life history traits could enhance or suppress their activity. We show that larger bodied species have lower levels of ERV activity by reconstructing the rate of ERV integration across 38 mammalian species. Body size explains 37% of the variance in ERV integration rate over the last 10 million years, controlling for the effect of confounding due to other life history traits. Furthermore, 68% of the variance in the mean age of ERVs per genome can also be explained by body size. These results indicate that body size limits the number of recently replicating ERVs due to their detrimental effects on their host. To comprehend the possible mechanistic links between body size and ERV integration we built a mathematical model, which shows that ERV abundance is favored by lower body size and higher horizontal transmission rates. We argue that because retroviral integration is tumorigenic, the negative correlation between body size and ERV numbers results from the necessity to reduce the risk of cancer, under the assumption that this risk scales positively with body size. Our model also fits the empirical observation that the lifetime risk of cancer is relatively invariant among mammals regardless of their body size, known as Peto's paradox, and indicates that larger bodied mammals may have evolved mechanisms to limit ERV activity.https://doi.org/10.1371/journal.ppat.1004214
spellingShingle Aris Katzourakis
Gkikas Magiorkinis
Aaron G Lim
Sunetra Gupta
Robert Belshaw
Robert Gifford
Larger mammalian body size leads to lower retroviral activity.
PLoS Pathogens
title Larger mammalian body size leads to lower retroviral activity.
title_full Larger mammalian body size leads to lower retroviral activity.
title_fullStr Larger mammalian body size leads to lower retroviral activity.
title_full_unstemmed Larger mammalian body size leads to lower retroviral activity.
title_short Larger mammalian body size leads to lower retroviral activity.
title_sort larger mammalian body size leads to lower retroviral activity
url https://doi.org/10.1371/journal.ppat.1004214
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AT gkikasmagiorkinis largermammalianbodysizeleadstolowerretroviralactivity
AT aaronglim largermammalianbodysizeleadstolowerretroviralactivity
AT sunetragupta largermammalianbodysizeleadstolowerretroviralactivity
AT robertbelshaw largermammalianbodysizeleadstolowerretroviralactivity
AT robertgifford largermammalianbodysizeleadstolowerretroviralactivity