Human mitochondrial DNA is widely used as tool in many fields including evolutionary anthropology and population history, medical genetics, genetic genealogy, and forensic science. Many applications require detailed knowledge about the phylogenetic relationship of mtDNA variants. Although the phylogenetic resolution of global human mtDNA diversity has greatly improved as a result of increasing sequencing efforts of complete mtDNA genomes, an updated overall mtDNA tree is currently not available. In order to facilitate a better use of known mtDNA variation, we have constructed an updated comprehensive phylogeny of global human mtDNA variation, based on both coding-and control region mutations. This complete mtDNA tree includes previously published as well as newly identified haplogroups, is easily navigable, will be continuously and regularly updated in the future, and is online available at http://www.phylotree.org. © 2008 Wiley-Liss, Inc. KEY WORDS: mitochondrial DNA, phylogenetic tree, haplogroup, mtDNA variation, human evolution INTRODUCTIONUniparentally inherited portions of the human genome have important applications in a wide range of fields including evolutionary anthropology and population history (Jobling and Tyler-Smith, 2003;Torroni et al., 2006;Underhill and Kivisild, 2007), medical genetics (Krausz et al., 2004;Taylor and Turnbull, 2005), genetic genealogy (Blansit, 2006; Johnston and Thomas, 2003;Shriver and Kittles, 2004) as well as forensic science (Kayser, 2007). Recently, an updated haplogroup tree of the patrilineally inherited, non-recombining part of the human Y chromosome (NRY) was published (Karafet et al., 2008). Here, we present an updated phylogenetic tree of its matrilineal counterpart, the mitochondrial (mt)DNA. PROPERTIES OF mtDNAMtDNA represents the small fraction of our genome that does not reside in the cell's nucleus, but is contained in the energy-producing mitochondria. It is a circular, double-stranded molecule with a length of nearly 16.6 kilobase pairs that encodes proteins required for oxidative phosphorylation. Special features of mtDNA include matrilineal inheritance, lack of recombination, high copy number, and a higher evolutionary turn over rate as compared to nuclear DNA. It is assumed that all mtDNA types in the human gene pool can ultimately be traced Global Human mtDNA Tree E387 back to a common matrilineal ancestor that lived approximately 200,000 years ago in Africa (Behar et al., 2008b;Macaulay et al., 2005;Mishmar et al., 2003). MtDNA sequence variation thus evolved as a result of the sequential accumulation of mutations along maternally inherited lineages, which can be represented in a tree reflecting the phylogenetic relationships of known mtDNA variants. The importance of a detailed global mtDNA phylogeny has been addressed by several authors (Bandelt et al., 2005 Kivisild et al., 2006a;Richards, 2004;Salas et al., 2007;Torroni et al., 2006). Recently, a global mtDNA phylogeny based on 2959 coding region sequences was published as part of the MITOMAP dat...

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Whole-genome sequencing enables complete characterization of genetic variation, but geographic clustering of rare alleles demands many diverse populations be studied. Here we describe the Genome of the Netherlands (GoNL) Project, in which we sequenced the whole genomes of 250 Dutch parent-offspring families and constructed a haplotype map of 20.4 million single-nucleotide variants and 1.2 million insertions and deletions. The intermediate coverage (∼13×) and trio design enabled extensive characterization of structural variation, including midsize events (30-500 bp) previously poorly catalogued and de novo mutations. We demonstrate that the quality of the haplotypes boosts imputation accuracy in independent samples, especially for lower frequency alleles. Population genetic analyses demonstrate fine-scale structure across the country and support multiple ancient migrations, consistent with historical changes in sea level and flooding. The GoNL Project illustrates how single-population whole-genome sequencing can provide detailed characterization of genetic variation and may guide the design of future population studies.

Mutational events along the human mtDNA phylogeny are traditionally identified relative to the revised Cambridge Reference Sequence, a contemporary European sequence published in 1981. This historical choice is a continuous source of inconsistencies, misinterpretations, and errors in medical, forensic, and population genetic studies. Here, after having refined the human mtDNA phylogeny to an unprecedented level by adding information from 8,216 modern mitogenomes, we propose switching the reference to a Reconstructed Sapiens Reference Sequence, which was identified by considering all available mitogenomes from Homo neanderthalensis. This "Copernican" reassessment of the human mtDNA tree from its deepest root should resolve previous problems and will have a substantial practical and educational influence on the scientific and public perception of human evolution by clarifying the core principles of common ancestry for extant descendants.

The geographic origin and time of dispersal of Austroasiatic (AA) speakers, presently settled in south and southeast Asia, remains disputed. Two rival hypotheses, both assuming a demic component to the language dispersal, have been proposed. The first of these places the origin of Austroasiatic speakers in southeast Asia with a later dispersal to south Asia during the Neolithic, whereas the second hypothesis advocates pre-Neolithic origins and dispersal of this language family from south Asia. To test the two alternative models, this study combines the analysis of uniparentally inherited markers with 610,000 common single nucleotide polymorphism loci from the nuclear genome. Indian AA speakers have high frequencies of Y chromosome haplogroup O2a; our results show that this haplogroup has significantly higher diversity and coalescent time (17-28 thousand years ago) in southeast Asia, strongly supporting the first of the two hypotheses. Nevertheless, the results of principal component and "structure-like" analyses on autosomal loci also show that the population history of AA speakers in India is more complex, being characterized by two ancestral components-one represented in the pattern of Y chromosomal and EDAR results and the other by mitochondrial DNA diversity and genomic structure. We propose that AA speakers in India today are derived from dispersal from southeast Asia, followed by extensive sex-specific admixture with local Indian populations.