title: Genetic constraints and the adaptive evolution of rabies virus in nature.
abstract: We used a molecular evolutionary approach to investigate the species adaptation of rabies virus in nature. A maximum likelihood analysis of selection pressures revealed that the nucleoprotein (N) and glycoprotein (G) genes of natural viral isolates were highly constrained, especially at nonsynonymous sites, in contrast to the higher rates of nonsynonymous evolution observed in viruses subject to laboratory passage. Positive selection was only found at a single amino acid site--position 183 in the ectodomain of the G gene. The low rate of nonsynonymous evolution in natural isolates of rabies virus may be due to constraints imposed by the need to replicate in multiple cell types within the host, which in turn facilitates cross-species transmission, or because viral proteins are not subject to immune selection. Using known dates in the epidemiologic history of European viral isolates, we estimated that overall rates of nucleotide substitution in rabies virus were similar to those observed in other RNA viruses. Assuming that the average rate of synonymous change does not vary among species, we estimated that the current genetic diversity in lyssavirus genotype 1 may have arisen only during the last 500 years.
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom. Edward.Holmes@zoo.ox.ac.uk
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Woelk
authors.forename: Raid
authors.initials: R
authors.lastname: Kassis
authors.forename: Hervé
authors.initials: H
authors.lastname: Bourhy
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D000956:Antigens, Viral; D004285:Dogs; D019143:Evolution, Molecular; D005814:Genes, Viral; D006023:Glycoproteins / Q000235:genetics; D016013:Likelihood Functions; D008969:Molecular Sequence Data; D019251:Nucleocapsid / Q000235:genetics; D019590:Nucleocapsid Proteins; D010802:Phylogeny; D011820:Rabies virus / Q000235:genetics* / Q000502:physiology; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: D000956:Antigens, Viral; D006023:Glycoproteins; D019590:Nucleocapsid Proteins; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus; C099601:nucleocapsid protein, Rabies virus