Dataset Information

Phylogenetic network of the mtDNA haplogroup U in Northern Finland based on sequence analysis of the complete coding region by conformation-sensitive gel electrophoresis.

ABSTRACT: Mutations in mtDNA have accumulated sequentially, and maternal lineages have diverged to form population-specific genotypes. Classification of the genotypes has been made based on differences found in restriction fragment analysis of the coding region or in the sequence of the hypervariable segment I. Both methods have shortcomings, as the former may not detect all the important polymorphisms and the latter makes use of a segment containing hypervariable nucleotide positions. Here, we have used conformation-sensitive gel electrophoresis (CSGE) to detect polymorphisms within the coding region of mtDNA from 22 Finns belonging to haplogroup U. Sixty-three overlapping PCR fragments covering the entire coding region were analyzed by CSGE, and the fragments that differed in their migration pattern were sequenced. CSGE proved to be a sensitive and specific method for identifying mtDNA substitutions. The phylogenetic network of the 22 coding-region sequences constituted a perfect tree, free of homoplasy, and provided several previously unidentified common polymorphisms characterizing subgroups of U. After contrasting this data with that of hypervariable segment I, we concluded that position 16192 seems to be prone to recurrent mutations and that position 16270 has experienced a back mutation. Interestingly, all 22 samples were found to belong to subcluster U5, suggesting that this subcluster is more frequent in Finns than in other European populations. Complete sequence data of the mtDNA yield a more reliable phylogenetic network and a more accurate classification of the haplogroups than previous ones. In medical genetics, such networks may help to decide between a rare polymorphism and a pathogenic mutation; in population genetics, the networks may enable more detailed analyses of population history and mtDNA evolution.

SUBMITTER: Finnila S

PROVIDER: S-EPMC1288139 | biostudies-literature | 2000 Mar

REPOSITORIES: biostudies-literature

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Phylogenetic network of the mtDNA haplogroup U in Northern Finland based on sequence analysis of the complete coding region by conformation-sensitive gel electrophoresis.

Finnilä S S Hassinen I E IE Ala-Kokko L L Majamaa K K

American journal of human genetics 20000301 3

Mutations in mtDNA have accumulated sequentially, and maternal lineages have diverged to form population-specific genotypes. Classification of the genotypes has been made based on differences found in restriction fragment analysis of the coding region or in the sequence of the hypervariable segment I. Both methods have shortcomings, as the former may not detect all the important polymorphisms and the latter makes use of a segment containing hypervariable nucleotide positions. Here, we have used ...[more]

PMID: 10712215

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Project description:BACKGROUND: Human genetic diversity observed in Indian subcontinent is second only to that of Africa. This implies an early settlement and demographic growth soon after the first 'Out-of-Africa' dispersal of anatomically modern humans in Late Pleistocene. In contrast to this perspective, linguistic diversity in India has been thought to derive from more recent population movements and episodes of contact. With the exception of Dravidian, which origin and relatedness to other language phyla is obscure, all the language families in India can be linked to language families spoken in different regions of Eurasia. Mitochondrial DNA and Y chromosome evidence has supported largely local evolution of the genetic lineages of the majority of Dravidian and Indo-European speaking populations, but there is no consensus yet on the question of whether the Munda (Austro-Asiatic) speaking populations originated in India or derive from a relatively recent migration from further East. RESULTS: Here, we report the analysis of 35 novel complete mtDNA sequences from India which refine the structure of Indian-specific varieties of haplogroup R. Detailed analysis of haplogroup R7, coupled with a survey of approximately 12,000 mtDNAs from caste and tribal groups over the entire Indian subcontinent, reveals that one of its more recently derived branches (R7a1), is particularly frequent among Munda-speaking tribal groups. This branch is nested within diverse R7 lineages found among Dravidian and Indo-European speakers of India. We have inferred from this that a subset of Munda-speaking groups have acquired R7 relatively recently. Furthermore, we find that the distribution of R7a1 within the Munda-speakers is largely restricted to one of the sub-branches (Kherwari) of northern Munda languages. This evidence does not support the hypothesis that the Austro-Asiatic speakers are the primary source of the R7 variation. Statistical analyses suggest a significant correlation between genetic variation and geography, rather than between genes and languages. CONCLUSION: Our high-resolution phylogeographic study, involving diverse linguistic groups in India, suggests that the high frequency of mtDNA haplogroup R7 among Munda speaking populations of India can be explained best by gene flow from linguistically different populations of Indian subcontinent. The conclusion is based on the observation that among Indo-Europeans, and particularly in Dravidians, the haplogroup is, despite its lower frequency, phylogenetically more divergent, while among the Munda speakers only one sub-clade of R7, i.e. R7a1, can be observed. It is noteworthy that though R7 is autochthonous to India, and arises from the root of hg R, its distribution and phylogeography in India is not uniform. This suggests the more ancient establishment of an autochthonous matrilineal genetic structure, and that isolation in the Pleistocene, lineage loss through drift, and endogamy of prehistoric and historic groups have greatly inhibited genetic homogenization and geographical uniformity.

Project description:BACKGROUND:Although our microbial community and genomes (the human microbiome) outnumber our genome by several orders of magnitude, to what extent the human host genetic complement informs the microbiota composition is not clear. The Human Microbiome Project (HMP) Consortium established a unique population-scale framework with which to characterize the relationship of microbial community structure with their human hosts. A wide variety of taxa and metabolic pathways have been shown to be differentially distributed by virtue of race/ethnicity in the HMP. Given that mtDNA haplogroups are the maternally derived ancestral genomic markers and mitochondria's role as the generator for cellular ATP, characterizing the relationship between human mtDNA genomic variants and microbiome profiles becomes of potential marked biologic and clinical interest. RESULTS:We leveraged sequencing data from the HMP to investigate the association between microbiome community structures with its own host mtDNA variants. 15 haplogroups and 631 mtDNA nucleotide polymorphisms (mean sequencing depth of 280X on the mitochondria genome) from 89 individuals participating in the HMP were accurately identified. 16S rRNA (V3-V5 region) sequencing generated microbiome taxonomy profiles and whole genome shotgun sequencing generated metabolic profiles from various body sites were treated as traits to conduct association analysis between haplogroups and host clinical metadata through linear regression. The mtSNPs of individuals with European haplogroups were associated with microbiome profiles using PLINK quantitative trait associations with permutation and adjusted for multiple comparisons. We observe that among 139 stool and 59 vaginal posterior fornix samples, several haplogroups show significant association with specific microbiota (q-value < 0.05) as well as their aggregate community structure (Chi-square with Monte Carlo, p < 0.005), which confirmed and expanded previous research on the association of race and ethnicity with microbiome profile. Our results further indicate that mtDNA variations may render different microbiome profiles, possibly through an inflammatory response to different levels of reactive oxygen species activity. CONCLUSIONS:These data provide initial evidence for the association between host ancestral genome with the structure of its microbiome.

Dataset Information

Phylogenetic network of the mtDNA haplogroup U in Northern Finland based on sequence analysis of the complete coding region by conformation-sensitive gel electrophoresis.

Publications

Phylogenetic network of the mtDNA haplogroup U in Northern Finland based on sequence analysis of the complete coding region by conformation-sensitive gel electrophoresis.

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