Median Networks: Speedy Construction and Greedy Reduction, One Simulation, and Two Case Studies from Human mtDNA

Abstract

Molecular data sets characterized by few phylogenetically informative characters with a broad spectrum of mutation rates, such as intraspecific controlregion sequence variation of human mitochondrial DNA (mtDNA), can be usefully visualized in the form of median networks. Here we provide a step-by-step guide to the construction of such networks by hand. We improve upon a previously implemented algorithm by outlining an efficient parametrized strategy amenable to large data sets, greedy reduction, which makes it possible to reconstruct some of the confounding recurrent mutations. This entails some postprocessing as well, which assists in capturing more parsimonious solutions. To simplify the creation of the resulting network by hand, we describe a speedy approach to network construction, based on a careful planning of the processing order. A coalescent simulation tailored to human mtDNA variation 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 comparison of characters in the two hypervariable segments of the human mtDNA control region in the light of the worldwide control-region sequence database, as well as additional restriction fragment length polymorphism information. We conclude that only a minority of the mutations that hit the second segment occur at sites that would have a mutation rate comparable to those at most sites in the first segment. Discarding the known "noisy" sites of the second segment enhances the analysis.

Revisiting the role of the Himalayas in peopling Nepal: insights from mitochondrial genomes

“…42 The reduced median networks of haplogroups of interest were constructed by using the network 4.510 program (http://www.fluxus-engineering.com/sharenet.htm) and adjusted manually (Figures 4 and 5). 43 The ages of the lineages G2a2 (further defined by mutation 16193 and named G2a2 tentatively) and M9a1a2a (characterized by mutations 16145, 16316 and a back mutation at site 16362, and designated as M9a1a2a) (Table 4) were estimated by using the r statistic 44,45 with the suggested calibration rates. 44,46 RESULTS AND DISCUSSION On the basis of the combined information from control-region and partial coding-region segments, the majority (96.34%; 237/246) of the Nepalese mtDNAs could unambiguously be allocated into the defined haplogroups of East Eurasian (36.59%; 90/246), 1,[20][21][22][23][24][25] Table S1, Supplementary Material online), 5 and this pattern remains almost stable for both the East Eurasian (45.11%; 189/419) and South Asian (47.49%; 199/419) components after taking into account the recently reported Nepalese mtDNA data.…”

“…Afterwards, we further compared the phylogenetic affinity of the East Eurasian lineages observed in Nepalese (including haplogroups A11, C, G2a, M9a, F1c and Z; Figures 4 and 5) with those from the neighboring regions, for example, Tibet, northeast and northwest India, by means of median networks. 43 On the basis of the constructed networks (Figures 4 and 5), several features could be observed: (1) the Nepalese share some basal or internal haplotypes with the Tibetans; (2) the Nepalese harbor a number of unique haplotypes at the terminal level, most of which branched off directly from the nodes occupied almost exclusively by the Tibetan lineages and (3) only a few haplotypes are shared sporadically between the Nepalese and the northern Indians. Taken together, the Nepalese lineages of East Eurasian ancestry generally show much closer affinity with the ones from Tibet, albeit a few mtDNA haplotypes, likely resulted from recent gene flow, were shared between the Nepalese and northern (including northeast) Indians (Figures 4 and 5).…”

“…To get some hint at the arrival time of the lineages, we have focused on two clades from haplogroups G2a and M9a1a2 simply because both clades contain the Nepalese haplotypes at their terminal branch or basal node and likely have differentiated in Nepal; estimating their ages would then help to 43 The data used here were collected from this study (Supplementary Table S1) and the literature ( Table 1). The sequence variation used for network construction was confined to segment 16047-16497.…”

Ancient links between Siberians and Native Americans revealed by subtyping the Y chromosome haplogroup Q1a

“…For the network construction, STR variants were weighted (with a weight assigned to a range of variance values) following the distribution of the number of mutations at character. 32 Loci DYS385a and DYS385b were excluded from the median joining network analysis, because an unambiguous assignment of the alleles to these loci is impossible without their separate typing. In the network construction and the age calculation procedures, the allele sizes for DYS389II were determined with the subtraction of DYS389I.…”

The molecular epidemiology of parasite infections: Tools and applications

“…Character conflict is often represented by a split network, where parallel edges connect the nodes, while reticulate networks, where some nodes have more than two parents, are often used as an explicit representation of complex evolutionary events [27]. A number of different network construction methods are available, including median networks [28], neighbour-nets [29] and reticulograms [30].…”