title: Limited variation during circulation of a polyomavirus in the human population involves the COCO-VA toggling site of Middle and Alternative T-antigen(s).
abstract: We have recently shown that the trichodysplasia spinulosa-associated polyomavirus (TSPyV) belongs to a large monophyletic group of mammalian polyomaviruses that experienced accelerated codon-constrained Val-Ala (COCO-VA) toggling at a protein site common to both Middle and Alternative T-antigens (MT/ALTO). Here we analyzed thirteen, mostly newly sequenced TSPyV genomes, representing ~40% of reported TS disease cases world-wide. We found two deletions and 30 variable sites (≤0.6%) that included only four sites with non-synonymous substitutions (NSS). One NSS site was under positive selection in the exon shared by Small and Middle T antigens, while three others were segregated in MT/ALTO. Two MT/ALTO sites covaried with five sites elsewhere in the genome and determined separation of twelve TSPyVs into two most populous phylogenetic lineages. The other, most distant TSPyV was distinguished by NSS at the COCO-VA site, observed for the first time during intra-species evolution. Our findings reveal a connection between micro- and macro-evolution of polyomaviruses.
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Siamaque
authors.initials: S
authors.lastname: Kazem
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Chris
authors.initials: C
authors.lastname: Lauber
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Els
authors.initials: E
authors.lastname: van der Meijden
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Kooijman
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119899 Moscow, Russia.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Kravchenko
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: m.c.w.feltkamp@lumc.nl.
authors.forename: Mariet C W
authors.initials: MC
authors.lastname: Feltkamp
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119899 Moscow, Russia; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119899 Moscow, Russia. Electronic address: a.e.gorbalenya@lumc.nl.
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Gorbalenya
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D000957:Antigens, Viral, Tumor / Q000235:genetics* / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics*; D016679:Genome, Viral / Q000235:genetics; D006801:Humans; D016366:Open Reading Frames / Q000235:genetics; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011120:Polyomavirus / Q000235:genetics* / Q000276:immunology; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D000957:Antigens, Viral, Tumor; D004279:DNA, Viral
keywords: Alternative T antigen; Codon-constrained Val-Ala (COCO-VA) toggling; Covariation; Intrinsically disordered protein; Middle T antigen; Phylogeny; Polyomavirus; Polyomavirus adaptation to human population; Positive selection; SLiM; Short linear motif; Small T antigen; TSPyV; Trichodysplasia spinulosa-associated polyomavirus