Massive parallel expansions of Methuselah/Methuselah‐like receptors in schizophoran Diptera

Abstract

The Methuselah/Methuselah-like (Mth/Mthl) family of G-protein coupled receptors (GPCRs) is represented by 16 homologs in the fruit fly Drosophila melanogaster. Three of them have thus far been functionally characterized and found to play critical roles in cell adhesion, immunity, lifespan, and oxidative stress regulation. Evolutionary studies have shown that the large number of D. melanogaster Mth/Mthl GPCRs arose by at least two rounds of gene duplications. The first produced the "mth superclade" subfamily and was followed by the expansion of the "melanogaster subgroup" cluster within the "mth superclade" of Mth/Mthl GPCRs. The adaptive significance of the Mth/Mthl receptor repertoire expansion in Drosophila remains elusive. Studying the Mth/Mthl gene family content in newly available dipteran genomes, we find that the first expansion of the mthl superclade predates the diversification of schizophoran Diptera approximately 65 million years ago. Unexpectedly, we further find that the subsequent expansion of the melanogaster subgroup cluster was paralleled by independent mth superclade Mth/Mthl GPCR expansions in other schizophoran clades (Muscidae and Tephritidae). Our study thus reveals an even more dynamic diversification of mth superclade GPCRs than previously appreciated and linked to the emergence of schizophoran flies, the most dramatic radiation in the dipteran tree of life.

G protein-coupled receptors that influence lifespan of human and animal models

“…The Mth/Mthl gene family arose in early metazoans and, as evolution progressed, underwent numerous extinction and expansion events that made it abundant in insects but absent in vertebrates (Patel et al 2012 ; de Mendoza et al 2016 ; Friedrich et al 2018 ). Phylogenetic analyzes of Mth protein have shown that it has undergone an unusually high level of adaptive amino acid divergence concentrated in the intra- and extracellular loop domains as an evolutionary strategy in a signal transduction pathway that can modulate lifespan in nature (Schmidt et al 2000 ).…”