Not so unique to Primates: The independent adaptive evolution of TRIM5 in Lagomorpha lineage

The plethora of restriction factors with the ability to inhibit the replication of retroviruses have been widely studied and genetic hallmarks of evolutionary selective pressures in Primates have been well documented. One example is the tripartite motif-containing protein 5 alpha (TRIM5 alpha), a cytoplasmic factor that restricts retroviral infection in a species-specific fashion. In Lagomorphs, similarly to what has been observed in Primates, the specificity of TRIM5 restriction has been assigned to the PRYSPRY domain. In this study, we present the first insight of an intra-genus variability within the Lagomorpha TRIM5 PRYSPRY domain. Remarkably, and considering just the 32 residue-long v1 region of this domain, the deduced amino acid sequences of Daurian pika (Ochotona dauurica) and steppe pika (O. pusilla) evidenced a high divergence when compared to the remaining Ochotona species, presenting values of 44% and 66% of amino acid differences, respectively. The same evolutionary pattern was also observed when comparing the v1 region of two Sylvilagus species members (47% divergence). However, and unexpectedly, the PRYSPRY domain of Lepus species exhibited a great conservation. Our results show a high level of variation in the PRYSPRY domain of Lagomorpha species that belong to the same genus. This suggests that, throughout evolution, the Lagomorpha TRIM5 should have been influenced by constant selective pressures, likely as a result of multiple different retroviral infections.