Influence of finite-sites mutation, population subdivision and sampling schemes on patterns of nucleotide...

Molecular hyperdiversity has been documented in viruses, prokaryotes and eukaryotes. Such organisms undermine the assumptions of the infinite-sites mutational model, because multiple mutational events at a site comprise a non-negligible portion of polymorphisms. Moreover, different sampling schemes of individuals from species with subdivided populations can profoundly influence resulting patterns and interpretations of molecular variation. Inspired by molecular hyperdiversity in the nematode Caenorhabditis sp. 5, which exhibits average pairwise differences among synonymous sites of >5% as well as modest population structure, we investigated via coalescent simulation the joint effects of a finite-sites mutation (FSM) process and population subdivision on the variant frequency spectrum. From many demes interconnected through a stepping-stone migration model, we constructed local samples from a single deme, pooled samples from several demes and scattered samples of a single individual from numerous demes. Compared with a single panmictic population at equilibrium, we find that high population mutation rates induce a deficit of rare variants (positive Tajima's D) under a FSM model. Population structure also induces such a skew for local samples when migration is high and for pooled samples when migration is low. Contrasts of sampling schemes for C. sp. 5 imply high mutational input coupled with high migration. We propose that joint analysis of local, pooled and scattered samples for species with subdivided populations provides a means of improving inference of demographic history, by virtue of the partially distinct patterns of polymorphism that manifest when sequences are analyzed according to differing sampling schemes.