Human enteroviruses consist of more than 60 serotypes, reflecting a wide ra
nge of evolutionary divergence. They have been genetically classified into
four clusters on the basis of sequence homology in the coding region of the
single-stranded RNA genome. To explore further the genetic relationships b
etween human enteroviruses and to characterize the evolutionary mechanisms
responsible for variation, previously sequenced genomes were subjected to d
etailed comparison. Bootstrap and genetic similarity analyses were used to
systematically scan the alignments of complete genomic sequences. Bootstrap
analysis provided evidence from an early recombination event at the juncti
on of the 5' noncoding and coding regions of the progenitors of the current
clusters. Analysis within the genetic clusters indicated that enterovirus
prototype strains include intraspecies recombinants. Recombination breakpoi
nts were detected in all genomic regions except the capsid protein coding r
egion. Our results suggest that recombination is a significant and relative
ly frequent mechanism in the evolution of enterovirus genomes.