Abstract
The Receptor Transporter Protein (RTP) family is present in most, if not all jawed vertebrates. Most of our knowledge of this protein family comes from studies on mammalian RTPs, which are multi-function proteins that regulate cell-surface G-protein coupled receptor levels, influence olfactory system development, regulate immune signaling, and directly inhibit viral infection. However, mammals comprise less than one-tenth of extant vertebrate species, and our knowledge about the expression, function, and evolution of non-mammalian RTPs is limited. Here, we explore the evolutionary history of RTPs in vertebrates. We identify signatures of positive selection in many vertebrate RTP clades and characterize multiple, independent expansions of the RTP family outside of what has been described in mammals. We find a striking expansion of RTPs in the African clawed frog, Xenopus laevis, with 11 RTPs in this species as opposed to 1 to 4 in most other species. RNA sequencing revealed that most X. laevis RTPs are upregulated following immune stimulation. In functional assays, we demonstrate that at least three of these X. laevis RTPs inhibit infection by RNA viruses, suggesting that RTP homologs may serve as antiviral effectors outside of Mammalia.
Highlights
Receptor Transporter Proteins (RTPs) were initially identified as regulators of chemosensory receptors [1]
We investigate the evolutionary history of RTPs and identify antiviral RTPs in the African clawed frog, Xenopus laevis
A maximum-likelihood tree generated from an alignment of 303 vertebrate RTPs (File A in S1 File) shows that non-mammalian RTPs generally form distinct clades among related species, consistent with a model in which intragenomic RTP expansions have typically resulted from more recent duplication events rather than ancient duplications (Fig 1A)
Summary
Receptor Transporter Proteins (RTPs) were initially identified as regulators of chemosensory receptors [1]. There are four RTPs: RTP1s, RTP2, RTP3, and RTP4. Functional-genomic analysis reveals intraspecies diversification of antiviral RTPs in Xenopus laevis. Other relevant data are within the manuscript and its Supporting Information Files
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