Methuselah proteins in Drosophila: Structural and evolutionary insights from mathematical genomics

This study provides a quantitative and comprehensive analysis of 18 Methuselah (mth) protein variants from fruit flies, which are part of the G-protein-coupled receptor (GPCR) family and are implicated in aging and longevity. Phylogenetic analysis identified two major clades of mth proteins, with the first clade indicating conserved functions across Drosophila species and the second clade reflecting gene duplication and diversification. The study found five distinct functional subclasses of mth proteins through amino acid frequency and poly-string analyses, linked to their structural diversity and role in longevity. Structural topology and post-translational modifications reveal similarities with G-protein-coupled receptors (GPCRs), suggesting that mth proteins are crucial for signal transduction and cellular health. Variability in propeptide cleavage sites and intrinsic protein disorder further highlight adaptive roles in signaling. The findings underscore the importance of a quantitative approach to studying Methuselah genes, offering insights into their functional versatility and evolutionary dynamics. This enhanced quantitative understanding contributes to advancing research on aging and longevity.