title: Evidence of recombination among early-vaccination era measles virus strains.
abstract: BACKGROUND
  The advent of live-attenuated vaccines against measles virus during the 1960'ies changed the circulation dynamics of the virus. Earlier the virus was indigenous to countries worldwide, but now it is mediated by a limited number of evolutionary lineages causing sporadic outbreaks/epidemics of measles or circulating in geographically restricted endemic areas of Africa, Asia and Europe. We expect that the evolutionary dynamics of measles virus has changed from a situation where a variety of genomic variants co-circulates in an epidemic with relatively high probabilities of co-infection of the individual to a situation where a co-infection with strains from evolutionary different lineages is unlikely.
  
  
  RESULTS
  We performed an analysis of the partial sequences of the hemagglutinin gene of 18 measles virus strains collected in Denmark between 1965 and 1983 where vaccination was first initiated in 1987. The results were compared with those obtained with strains collected from other parts of the world after the initiation of vaccination in the given place. Intergenomic recombination among pre-/early-vaccination strains is suggested by 1) estimations of linkage disequilibrium between informative sites, 2) the decay of linkage disequilibrium with distance between informative sites and 3) a comparison of the expected number of homoplasies to the number of apparent homoplasies in the most parsimonious tree. No significant evidence of recombination could be demonstrated among strains circulating at present.
  
  
  CONCLUSIONS
  We provide evidence that recombination can occur in measles virus and that it has had a detectable impact on sequence evolution of pre-vaccination samples. We were not able to detect recombination from present-day sequence surveys. We believe that the decreased rate of visible recombination may be explained by changed dynamics, since divergent strains do not meet very often in current epidemics that are often spawned by a single sequence type. Signs of pre-vaccination recombination events in the present-day sequences are not strong enough to be detectable.
authors.affiliation: Bioinformatics Research Center (BiRC), University of Aarhus, Hoegh Guldbergs Gade 10, DK-8000 Aarhus C, Denmark. mheide@birc.au.dk
authors.forename: Mikkel H
authors.initials: MH
authors.lastname: Schierup
authors.forename: Carl H
authors.initials: CH
authors.lastname: Mordhorst
authors.forename: Claude P
authors.initials: CP
authors.lastname: Muller
authors.forename: Laurids S
authors.initials: LS
authors.lastname: Christensen
mesh_terms: D001483:Base Sequence; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D005828:Genetics, Population; D016679:Genome, Viral; D006389:Hemagglutinins, Viral / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008457:Measles / Q000453:epidemiology / Q000517:prevention & control; D008458:Measles Vaccine; D008459:Measles virus / Q000235:genetics*; D008957:Models, Genetic; D008962:Models, Theoretical; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D011995:Recombination, Genetic; D012689:Sequence Homology, Nucleic Acid; D014613:Vaccines, Attenuated
chemical_list: D006389:Hemagglutinins, Viral; D008458:Measles Vaccine; D014613:Vaccines, Attenuated