Larger mammalian body size leads to lower retroviral activity

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.

Figure 1. (a) Correlation between mean age of all ERV integrations and body mass from the genomes of 38 mammals.

Body mass is log-transformed, and the mean ages are calculated correcting for the substitution rate (R² = 0.68, P<0.001). (b, c, d) The relationship between ERV count and body mass for the number of ERV integrations acquired over the last 10 my, between 10–35 mya and >35 mya in the genomes of 38 mammals (both values log-transformed). The trend lines representing the slope for the regression, corrected for phylogenetic non-independence, and accompanying P-values are plotted. We have taken into account the effect of body size on substitution rate in calculating the ages.

Figure 2. (a) Correlation between ERV count and body mass for the number of ERV integrations acquired over the last 10 my.

(b) Correlation between mean age of all ERV integrations and body mass from the genomes of 38 mammals. Body mass is log-transformed, and the mean ages are calculated correcting for the substitution rate. We have not taken into account the effect of body size on substitution rate in calculating the ages.

Figure 3. Correlations of number of ERVs against body mass (both log-transformed) by ERV class.

Figure 4. Age distribution of ERVs by class.

Figure 5. The effect of body size (B) for different horizontal transmission rates (λ) on the structure of the population at equilibrium.

At high rates of horizontal transmission (λ), the proportion of infected individuals reaches a plateau for increasing body sizes. Moreover, in this case, for larger body sizes, there is a greater proportion of exogenous retrovirus infections than there are endogenous ones.