Phylogenetic network for European mtDNA

Abstract

The sequence in the first hypervariable segment (HVS-I) of the control region has been used as a source of evolutionary information in most phylogenetic analyses of mtDNA. Population genetic inference would benefit from a better understanding of the variation in the mtDNA coding region, but, thus far, complete mtDNA sequences have been rare. We determined the nucleotide sequence in the coding region of mtDNA from 121 Finns, by conformation-sensitive gel electrophoresis and subsequent sequencing and by direct sequencing of the D loop. Furthermore, 71 sequences from our previous reports were included, so that the samples represented all the mtDNA haplogroups present in the Finnish population. We found a total of 297 variable sites in the coding region, which allowed the compilation of unambiguous phylogenetic networks. The D loop harbored 104 variable sites, and, in most cases, these could be localized within the coding-region networks, without discrepancies. Interestingly, many homoplasies were detected in the coding region. Nucleotide variation in the rRNA and tRNA genes was 6%, and that in the third nucleotide positions of structural genes amounted to 22% of that in the HVS-I. The complete networks enabled the relationships between the mtDNA haplogroups to be analyzed. Phylogenetic networks based on the entire coding-region sequence in mtDNA provide a rich source for further population genetic studies, and complete sequences make it easier to differentiate between disease-causing mutations and rare polymorphisms.

Figure 1

Phylogenetic network based on variation in the coding sequence in mtDNA from 192 Finnish subjects. The outgroup is mtDNA from an African individual (Ingman et al. ; GenBank accession number AF346980). Numbers inside the nodes denote samples. Unless marked otherwise, the polymorphic variants, shown on the lines connecting the nodes, are transitions. Superscripts indicate transversions or inserted nucleotides. Position 10398 was down-weighted in the analysis, but otherwise the weights of the nucleotide positions were equal. A reticulation due to variation at position 15884 within haplogroup W was resolved by assuming a back mutation in samples 72 and 73. The following substitutions were common to all samples: 3423G→T, 4985G→A, 9559G→C, 11335T→C, 13702G→C, 14199G→T, 14272G→C, 14365G→C, 14368G→C, and 3106delC. i = insertion; d 9bp = 9-bp deletion in the CO II-tRNA^Lys intergenic region; @ = back mutation; h = heteroplasmic mutation.

Figure 2

Phylogenetic network of mtDNA, based on variation in the D-loop sequence. The outgroup is mtDNA from an African individual (Ingman et al. ; GenBank accession number AF346980). Fast-evolving sites 303, 311, and 16519 were not included in the network. i = insertion; d = deletion; @ = back mutation. The superscripts indicate transversions or inserted or deleted nucleotides. For further information, see the legend to figure 1.