Research Article: Larger Mammalian Body Size Leads to Lower Retroviral Activity

Date Published: July 17, 2014

Publisher: Public Library of Science

Author(s): Aris Katzourakis, Gkikas Magiorkinis, Aaron G. Lim, Sunetra Gupta, Robert Belshaw, Robert Gifford, Carlo Maley.

http://doi.org/10.1371/journal.ppat.1004214

Abstract

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.

Partial Text

Mammalian genomes contain large numbers of endogenous retroviruses (ERVs), derived from multiple independent germline invasions over evolutionary time. The human genome contains 31–40 such ERV invasions, termed ‘families’, each derived from a distinct ancestral exogenous retrovirus [1], [2]. These ERVs can continue proliferating after the initial germline invasion until they are inactivated, either through the acquisition of substitutions that occur at the host background level (∼10−3 per base per my) or by recombinational deletion [3], [4]. Most ERV families proliferate by reinfection, although some ERVs occasionally switch from reinfecting germline cells to an entirely intracellular life, and this switch can lead to an increase in the size of the ERV family [5]. As a result of these processes, ERVs have come to occupy ∼5–10% of their hosts’ genomes [6], [7].

We identified 84,223 ERVs, of which 27,711 have integrated in the last 10 my across 38 species of mammal (Table 2). We find that the number of ERV integrations in mammals is negatively correlated to body size. This correlation can explain 37% of the variance in the number of ERV integrations over the past 10 my. We have controlled for confounding variables such as life history and sexual selection, and also confirmed robustness to variation in effective population size. Nevertheless body size can be influenced by other parameters, and it is possible that other factors (e.g. environmental, dietary) contribute to both body size and ERV abundance, thereby explaining part of the remaining variance; for example they might account for the residual variance of outliers (e.g. Dasypus Novemcinctus and Canis familiaris). Interestingly, Microcebus murinus, whose life history evolved rapidly due to its isolation in Madagascar [29], might be expected to be a significant outlier in the correlation, but is very close to the regression line. Perhaps the global distribution and geographic isolation of a species is another determinant of the variance in ERV abundance.

 

Source:

http://doi.org/10.1371/journal.ppat.1004214

 

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