The evolutionary kaleidoscope of rhodopsins

Rhodopsins are widely distributed across all domains of life where they perform a plethora of functions through conversion of electromagnetic radiation into physicochemical signals(Rozenberg et al., 2021). As a result of an extensive survey on available genomic and metagenomic sequencing data, we report the existence of novel clades and exotic sequence motifs scattered through the evolutionary radiations of both Type-1 and -3 rhodopsins that will likely enlarge the optogenetics toolbox(Gushchin and Gordeliy, 2018; Kandori, 2021). We expand the typical rhodopsin blueprint by showing that a highly conserved (and functionally important) arginine residue (i.e., Arg82) was substituted multiple times during evolution by an extensive amino acid spectrum. We propose the umbrella term Alt-rhodopsins (AltR) for all such proteins that depart Arg82 orthodoxy. The newly uncovered diversity helped us to address the larger evolutionary scenario of microbial rhodopsins and to unearth clues about the Type-3 (heliorhodopsins) radiation. Thus, we propose that the proto-heliorhodopsins were a eukaryotic innovation that was mobilized by giant viral intermediates before their subsequent diversification into the extant Type-3 rhodopsins.