Evolutionary dynamics of mammalian mRNA untranslated regions by comparative analysis of orthologous human, artiodactyl and rodent gene pairs

Abstract

Most evolutionary studies based on molecular data refer to the portion of genomes encoding for proteins. Today, however, more and more attention is paid to the so-called ‘non-coding’ regions, which constitute a notable portion of the metazoan nuclear genome. Among them, the untranslated regions of messenger RNAs (mRNA UTRs) are particularly important, as they are involved in the regulation of gene expression, controlling translation efficiency as well as mRNA localization and stability. Up to now, only few studies have focused on the analysis of the compositional and structural features of UTRs, or carried out to investigate quantitatively their evolutionary dynamics. For this reason we have carried out an inter-order study on the evolutionary rate of 5′ and 3′ UTRs with respect to the corresponding coding region in 93 triplets of orthologous genes (selected through a phylogenetic approach, for a total of 645 625 nt) belonging to Primates (Homo sapiens), Artiodactyla (Bos taurus) and Rodentia (Mus spp.). Our study, that considered only likely orthologous genes, has revealed interesting features on the evolution of these regions concerning nucleotide substitution rate and indels and repetitive element distribution. UTRs from different genes showed a remarkable heterogeneity in the evolutionary dynamics, with some homologous so highly divergent to prevent their alignment, and other rather conserved, at least in some regions; most divergent sequence pairs were excluded from our analysis. The comparison between the nucleotide substitution rates calculated for 5′ and 3′ UTRs with those calculated on synonymous coding position allowed us to verify and measure the existence of functional constraints acting upon the UTRs of different genes which have shown, in many cases, a positive selection driven evolutionary dynamics.