Nucleotide sequence polymorphism in circoviruses.

Analysis of nucleotide diversity within six species of circovirus showed consistently stronger purifying selection at nonsynonymous sites in the rep gene than on those in the cap gene. In addition, synonymous nucleotide diversity in the rep gene was significantly lower than that in the cap gene, suggesting functional constraint even at synonymous sites in rep, which was associated in all six species with strongly negative AT-skew. Of the six virus species examined, four species showed evidence of ongoing purifying selection at nonsynonymous polymorphic sites in the rep gene, indicating the presence of slightly deterious nonsynonymous variants in these populations. The rep gene of porcine circovirus 2 (PCV2) was unique, however, in showing a strong excess of rare nonsynonymous polymorphisms. The excess of rare nonsynonymous polymorphisms suggests a prolonged population bottleneck in PCV2, allowing slightly deleterious mutations to accumulate, followed by a population expansion during which selection to remove these variants has increased in effectiveness. Such a population history is consistent with the epidemiological evidence of a recent worldwide spread of PCV2.