ArticleScientific reports2026
Lineage-specific selection signals in the Growth arrest-specific protein 8 (GAS8) domain protein of Trypanosoma melophagium.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The Growth arrest-specific protein 8 (GAS8) domain-containing gene family (Orthogroup 6127at5690) is a highly conserved, single-copy orthologous group in the Trypanosoma taxa retained for codon-based evolutionary analysis (10 validated species). This family encodes a microtubule-associated protein implicated in cytoskeletal organization and flagellar motility. We conducted a genus-wide evolutionary analysis of the GAS8-domain protein, focusing on the Trypanosoma melophagium ortholog LSM04 004638. Maximum likelihood phylogenetic reconstruction, branch-specific and site-level codon-based selection analyses, ancestral sequence reconstruction, and Rosetta-based energetic estimation were performed. Despite strong purifying constraint consistent with essential cytoskeletal function, branch-level aBSREL detected a statistically significant signal compatible with episodic diversifying selection along the T. melophagium lineage (aBSREL: LRT = 6.72, Holm-corrected p = 0.0494). Site-level analyses identified two significant MEME codon sites (2 and 109; p = 0.00598 and p = 0.00916), corresponding to derived non-synonymous substitutions relative to the reconstructed ancestor (P2G and V106L); a third site (267) was suggestive but not significant (p = 0.08596). Branch-site codeml did not reach statistical significance (LRT = 1.7428, p = 0.1868, BH-FDR = 0.9339), although BEB highlighted site 2 (PP = 0.983) under the alternative model. These results are consistent with, but do not by themselves prove, limited lineage-specific adaptive refinement in an otherwise highly constrained cytoskeletal regulator; the signal should be regarded as method-dependent and statistically modest based on codeml branch-site test. A RELAX sensitivity test found no evidence that the focal-lineage signal is driven by relaxed constraint (K = 1.12, p = 0.697). Rosetta-based energetic comparisons across single- and double-reversion models consistently yielded positive [Formula: see text] values, but structural interpretation remains model-dependent and should be treated as hypothesis-generating rather than as direct evidence for altered function in vivo.
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