EMPIRICAL VALIDATION OF THE NEARLY NEUTRAL THEORY AT DIVERGENCE AND POPULATION GENOMIC SCALE USING 144 PLACENTAL...

By limiting the efficacy of selection, random drift is expected to play a major role in genome evolution. Formalizing this idea, the nearly-neutral theory predicts that the ratio of non-synonymous over synonymous polymorphism $\left({\pi }_N/{\pi }_S\right)$ within populations, and divergence $\left(d_N/d_S\right)$ between species, should both correlate negatively with $N_{\text{e}}$ . This has previously been tested in mammals and other groups. However, most studies have focused on either $d_N/d_S$ or on ${\pi }_N/{\pi }_S$ , thus not addressing the problem across evolutionary scales. In addition, many studies at the macro scale have used life-history traits (LHT) as a proxy of $N_{\text{e}}$ , assuming that large-bodied organisms have lower $N_{\text{e}}$ than small-bodied species. However, this assumption itself has rarely been validated against more objective measures of $N_{\text{e}}$ , such as genetic diversity ${\pi }_S=4N_{\text{e}}\mu$ , in part because ${\pi }_S$ estimates are scarce. Here we propose an integrative test of the nearly-neutral predictions on 150 mammalian species, using 6000 orthologous genes, spanning the macro and the micro-evolutionary scale, using for the latter a measure of heterozygosity on each of the assembled diploid genomes. At the micro scale, we observe, for the first time in mammalian nuclear genomes, a relationship between ${\pi }_N/{\pi }_S$ and ${\pi }_S$ . At the macro scale, we confirm the positive correlation between $d_N/d_S$ and LHT but, more importantly, establish that LHT and $d_N/d_S$ are correlated with ${\pi }_S$ , although weakly so. Together, these results provide the first global test of the nearly-neutral theory in mammals across time scales, suggesting all variables are correlated with a single hidden variable: $N_{\text{e}}$ .