title: Functional significance may underlie the taxonomic utility of single amino acid substitutions in conserved proteins.
abstract: We hypothesized that some amino acid substitutions in conserved proteins that are strongly fixed by critical functional roles would show lineage-specific distributions. As an example of an archetypal conserved eukaryotic protein we considered the active site of beta-tubulin. Our analysis identified one amino acid substitution--beta-tubulin F224--which was highly lineage specific. Investigation of beta-tubulin for other phylogenetically restricted amino acids identified several with apparent specificity for well-defined phylogenetic groups. Intriguingly, none showed specificity for "supergroups" other than the unikonts. To understand why, we analysed the beta-tubulin Neighbor-Net and demonstrated a fundamental division between core beta-tubulins (plant-like) and divergent beta-tubulins (animal and fungal). F224 was almost completely restricted to the core beta-tubulins, while divergent beta-tubulins possessed Y224. Thus, our specific example offers insight into the restrictions associated with the co-evolution of beta-tubulin during the radiation of eukaryotes, underlining a fundamental dichotomy between F-type, core beta-tubulins and Y-type, divergent beta-tubulins. More broadly our study provides proof of principle for the taxonomic utility of critical amino acids in the active sites of conserved proteins.
authors.affiliation: School of Medicine, Health Policy and Practice, BioMedical Research Center, University of East Anglia, Norwich NR4 7TJ, UK. k.tyler@uea.ac.uk
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Tyler
authors.forename: Gerd K
authors.initials: GK
authors.lastname: Wagner
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Katharina T
authors.initials: KT
authors.lastname: Huber
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D002417:Cattle; D017124:Conserved Sequence; D056890:Eukaryota / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D012984:Software; D014404:Tubulin / Q000235:genetics*
chemical_list: D005656:Fungal Proteins; D014404:Tubulin
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