Median networks: Speedy construction and greedy reduction, one simulation,and two case studies from human mtDNA

Molecular data sets characterized by few phylogenetically informative chara cters with a broad spectrum of mutation rates, such as intraspecific contro l-region sequence variation of human mitochondrial DNA (mtDNA), can be usef ully visualized in the form of median networks, Here we provide a step-by-s tep guide to the construction of such networks by hand, We improve upon a p reviously implemented algorithm by outlining an efficient parametrized stra tegy amenable to large data sets, greedy reduction, which makes it possible to reconstruct some of the confounding recurrent mutations. This entails s ome postprocessing as well, which assists in capturing more parsimonious so lutions. To simplify the creation of the resulting network by hand, we desc ribe a speedy approach to network construction, based on a careful planning of the processing order, A coalescent simulation tailored to human mtDNA v ariation in Eurasia testifies to the usefulness of reduced median networks, while highlighting notorious problems faced by all phylogenetic methods in this context. Finally, we discuss two case studies involving the compariso n of characters in the two hypervariable segments of the human mtDNA contro l region in the light of the worldwide control-region sequence database, as well as additional restriction fragment length polymorphism information. W e conclude that only a minority of the mutations that hit the second segmen t occur at sites that would have a mutation rate comparable to those at mos t sites in the first segment. Discarding the known "noisy" sites of the sec ond segment enhances the analysis. (C) 2000 Academic Press.