Phylogenetic structuring of intrinsic disorder and charge patterning in vertebrate Ermin
DOI:
https://doi.org/10.24193/subbbiol.2026.1.07Keywords:
Ermin (ERMN), Intrinsically disordered proteins (IDPs), Intrinsic disorder evolution, Sequence charge decoration (SCD), Phylogenetic comparative analysis (PGLS)Abstract
Ermin (ERMN) is an oligodendrocyte-enriched cytoskeletal protein implicated in myelin sheath formation and stability. Although previously described as intrinsically disordered, its evolutionary diversification across vertebrates has not been systematically examined. Here, we performed a comprehensive phylogenetic and comparative analysis of 159 vertebrate Ermin orthologs to characterize the evolution of intrinsic disorder and physicochemical sequence properties. Across all major vertebrate clades, Ermin consistently fulfilled criteria for highly intrinsically disordered proteins based on Average Disorder Score (ADS) and Percent of Predicted Disordered Residues (PPDR), demonstrating that extensive disorder represents a deeply conserved structural feature. Despite this conserved disorder abundance, the architectural organization of intrinsically disordered regions (IDRs) varied among lineages. Mammalian Ermin proteins exhibited increased fragmentation of long IDRs compared to birds, which retained largely continuous long-IDR segments, indicating that IDR partitioning evolves independently of total disorder content. Amino-acid composition analyses revealed conserved depletion of aromatic and bulky hydrophobic residues across vertebrates, combined with clade-structured variation in charged and disorder-promoting residues.
Phylogenetic generalized least squares (PGLS) analyses detected strong phylogenetic signal across disorder and electrostatic traits. Root-to-tip regressions revealed a significant directional decrease in mean hydrophobicity across vertebrate divergence, whereas disorder propensity and sequence charge decoration (SCD) did not exhibit consistent monotonic Fraction of charged residues (FCR) showed more modest evolutionary variation. Multivariate models further demonstrated that hydrophobicity, global charge density, and sequence charge decoration independently contribute to evolutionary variation in Ermin sequence architecture.
Together, these results indicate that Ermin evolution is characterized by architectural remodeling and compositional retuning of an already disordered scaffold rather than by progressive increases in intrinsic disorder. This study highlights IDR fragmentation and electrostatic organization as key evolutionary dimensions shaping the diversification of intrinsically disordered proteins across vertebrate lineages.
Article history: Received 27 February 2026; Revised 17 June 2026;
Accepted 17 June 2026; Available online 25 June 2026.
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