Larger Mammalian Body Size Leads to Lower Retroviral Activity
Aris Katzourakis1,*, Gkikas Magiorkinis1,2,*, Aaron G. Lim3, Sunetra Gupta1, Robert Belshaw4, Robert Gifford5
1Department of Zoology, University of Oxford, United Kingdom
2Virus Reference Department, Public Health England, London, United Kingdom
3Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, United Kingdom
4School of Biomedical and Healthcare Sciences, Plymouth University, Plymouth, United Kingdom
5MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom
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 or 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 or 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,underr 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.