An Expanding Universe of Mutational Signatures and Its Rapid Evolution in Single-Stranded RNA Viruses

The study of mutational processes in somatic genomes has gained recent momentum, uncovering a wide array of endogenous and exogenous factors associated with somatic changes. However, the overall landscape of mutational processes in germline mutations across the tree of life and associated evolutionary driving forces are rather unclear. In this study, we analyzed mutational processes in single-stranded RNA (ssRNA) viruses which are known to jump between different hosts with divergent exogenous environments. We found that mutational spectra in different ssRNA viruses differ significantly and are mainly associated with their genetic divergence. Surprisingly, host environments contribute much less significantly to the mutational spectrum, challenging the prevailing view that the exogenous cellular environment is a major determinant of the mutational spectrum in viruses. To dissect the evolutionary forces shaping viral spectra, we selected two important scenarios, namely the inter-host evolution between different viral strains as well as the intra-host evolution. In both scenarios, we found mutational spectra change significantly through space and time, strongly correlating with levels of natural selection. Combining the mutations across all ssRNA viruses, we identified a suite of mutational signatures with varying degrees of similarity to somatic signatures in humans, indicating universal and divergent mutational processes across the tree of life. Taken together, we unraveled an unprecedented dynamic landscape of mutational processes in ssRNA viruses, pinpointing important evolutionary forces shaping fast evolution of mutational spectra in different species.