Rectifying long-standing misconceptions about the ρ statistic for molecular dating.

When divided by a given mutation rate, the ρ (rho) statistic provides a simple estimator of the age of a clade within a phylogenetic tree by averaging the number of mutations from each sample in the clade to its root. However, a long-standing critique of the use of ρ in genetic dating has been quite often cited. Here we show that the critique is unfounded.

Mitogenome Diversity in Sardinians: A Genetic Window onto an Island's Past.

Sardinians are "outliers" in the European genetic landscape and, according to paleogenomic nuclear data, the closest to early European Neolithic farmers. To learn more about their genetic ancestry, we analyzed 3,491 modern and 21 ancient mitogenomes from Sardinia. We observed that 78.

Resolving the ancestry of Austronesian-speaking populations.

There are two very different interpretations of the prehistory of Island Southeast Asia (ISEA), with genetic evidence invoked in support of both. The "out-of-Taiwan" model proposes a major Late Holocene expansion of Neolithic Austronesian speakers from Taiwan. An alternative, proposing that Late Glacial/postglacial sea-level rises triggered largely autochthonous dispersals, accounts for some otherwise enigmatic genetic patterns, but fails to explain the Austronesian language dispersal.

A substantial prehistoric European ancestry amongst Ashkenazi maternal lineages.

The origins of Ashkenazi Jews remain highly controversial. Like Judaism, mitochondrial DNA is passed along the maternal line. Its variation in the Ashkenazim is highly distinctive, with four major and numerous minor founders.

Evaluating purifying selection in the mitochondrial DNA of various mammalian species.

Mitochondrial DNA (mtDNA), the circular DNA molecule inside the mitochondria of all eukaryotic cells, has been shown to be under the effect of purifying selection in several species. Traditional testing of purifying selection has been based simply on ratios of nonsynonymous to synonymous mutations, without considering the relative age of each mutation, which can be determined by phylogenetic analysis of this non-recombining molecule. The incorporation of a mutation time-ordering from phylogeny and of predicted pathogenicity scores for nonsynonymous mutations allow a quantitative evaluation of the effects of purifying selection in human mtDNA.

Mitochondrial DNA signals of late glacial recolonization of Europe from near eastern refugia.

Human populations, along with those of many other species, are thought to have contracted into a number of refuge areas at the height of the last Ice Age. European populations are believed to be, to a large extent, the descendants of the inhabitants of these refugia, and some extant mtDNA lineages can be traced to refugia in Franco-Cantabria (haplogroups H1, H3, V, and U5b1), the Italian Peninsula (U5b3), and the East European Plain (U4 and U5a). Parts of the Near East, such as the Levant, were also continuously inhabited throughout the Last Glacial Maximum, but unlike western and eastern Europe, no archaeological or genetic evidence for Late Glacial expansions into Europe from the Near East has hitherto been discovered.

Interdisciplinary approach to the demography of Jamaica.

Background: The trans-Atlantic slave trade dramatically changed the demographic makeup of the New World, with varying regions of the African coast exploited differently over roughly a 400 year period. When compared to the discrete mitochondrial haplotype distribution of historically appropriate source populations, the unique distribution within a specific source population can prove insightful in estimating the contribution of each population. Here, we analyzed the first hypervariable region of mitochondrial DNA in a sample from the Caribbean island of Jamaica and compared it to aggregated populations in Africa divided according to historiographically defined segments of the continent's coastline.

The Expansion of mtDNA Haplogroup L3 within and out of Africa.

Although fossil remains show that anatomically modern humans dispersed out of Africa into the Near East ∼100 to 130 ka, genetic evidence from extant populations has suggested that non-Africans descend primarily from a single successful later migration. Within the human mitochondrial DNA (mtDNA) tree, haplogroup L3 encompasses not only many sub-Saharan Africans but also all ancient non-African lineages, and its age therefore provides an upper bound for the dispersal out of Africa. An analysis of 369 complete African L3 sequences places this maximum at ∼70 ka, virtually ruling out a successful exit before 74 ka, the date of the Toba volcanic supereruption in Sumatra.

Ancient voyaging and Polynesian origins.

The "Polynesian motif" defines a lineage of human mtDNA that is restricted to Austronesian-speaking populations and is almost fixed in Polynesians. It is widely thought to support a rapid dispersal of maternal lineages from Taiwan ~4000 years ago (4 ka), but the chronological resolution of existing control-region data is poor, and an East Indonesian origin has also been proposed. By analyzing 157 complete mtDNA genomes, we show that the motif itself most likely originated >6 ka in the vicinity of the Bismarck Archipelago, and its immediate ancestor is >8 ka old and virtually restricted to Near Oceania.

Population expansion in the North African late Pleistocene signalled by mitochondrial DNA haplogroup U6.

Background: The archaeology of North Africa remains enigmatic, with questions of population continuity versus discontinuity taking centre-stage. Debates have focused on population transitions between the bearers of the Middle Palaeolithic Aterian industry and the later Upper Palaeolithic populations of the Maghreb, as well as between the late Pleistocene and Holocene.

Results: Improved resolution of the mitochondrial DNA (mtDNA) haplogroup U6 phylogeny, by the screening of 39 new complete sequences, has enabled us to infer a signal of moderate population expansion using Bayesian coalescent methods.

The archaeogenetics of Europe.

A new timescale has recently been established for human mitochondrial DNA (mtDNA) lineages, making mtDNA at present the most informative genetic marker system for studying European prehistory. Here, we review the new chronology and compare mtDNA with Y-chromosome patterns, in order to summarize what we have learnt from archaeogenetics concerning five episodes over the past 50,000 years which significantly contributed to the settlement history of Europe: the pioneer colonisation of the Upper Palaeolithic, the Late Glacial re-colonisation of the continent from southern refugia after the Last Glacial Maximum, the postglacial re-colonization of deserted areas after the Younger Dryas cold snap, the arrival of Near Easterners with an incipient Neolithic package, and the small-scale migrations along continent-wide economic exchange networks beginning with the Copper Age. The available data from uniparental genetic systems have already transformed our view of the prehistory of Europe, but our knowledge of these processes remains limited.

Mitochondrial echoes of first settlement and genetic continuity in El Salvador.

Background: From Paleo-Indian times to recent historical episodes, the Mesoamerican isthmus played an important role in the distribution and patterns of variability all around the double American continent. However, the amount of genetic information currently available on Central American continental populations is very scarce. In order to shed light on the role of Mesoamerica in the peopling of the New World, the present study focuses on the analysis of the mtDNA variation in a population sample from El Salvador.

Correcting for purifying selection: an improved human mitochondrial molecular clock.

There is currently no calibration available for the whole human mtDNA genome, incorporating both coding and control regions. Furthermore, as several authors have pointed out recently, linear molecular clocks that incorporate selectable characters are in any case problematic. We here confirm a modest effect of purifying selection on the mtDNA coding region and propose an improved molecular clock for dating human mtDNA, based on a worldwide phylogeny of > 2000 complete mtDNA genomes and calibrating against recent evidence for the divergence time of humans and chimpanzees.

The diversity present in 5140 human mitochondrial genomes.

We analyzed the current status (as of the end of August 2008) of human mitochondrial genomes deposited in GenBank, amounting to 5140 complete or coding-region sequences, in order to present an overall picture of the diversity present in the mitochondrial DNA of the global human population. To perform this task, we developed mtDNA-GeneSyn, a computer tool that identifies and exhaustedly classifies the diversity present in large genetic data sets. The diversity observed in the 5140 human mitochondrial genomes was compared with all possible transitions and transversions from the standard human mitochondrial reference genome.

Climate change and postglacial human dispersals in southeast Asia.

Modern humans have been living in Island Southeast Asia (ISEA) for at least 50,000 years. Largely because of the influence of linguistic studies, however, which have a shallow time depth, the attention of archaeologists and geneticists has usually been focused on the last 6,000 years--in particular, on a proposed Neolithic dispersal from China and Taiwan. Here we use complete mitochondrial DNA (mtDNA) genome sequencing to spotlight some earlier processes that clearly had a major role in the demographic history of the region but have hitherto been unrecognized.

mtDNA phylogeny and evolution of laboratory mouse strains.

Inbred mouse strains have been maintained for more than 100 years, and they are thought to be a mixture of four different mouse subspecies. Although genealogies have been established, female inbred mouse phylogenies remain unexplored. By a phylogenetic analysis of newly generated complete mitochondrial DNA sequence data in 16 strains, we show here that all common inbred strains descend from the same Mus musculus domesticus female wild ancestor, and suggest that they present a different mitochondrial evolutionary process than their wild relatives with a faster accumulation of replacement substitutions.

Multiplexed SNP typing of ancient DNA clarifies the origin of Andaman mtDNA haplogroups amongst South Asian tribal populations.

The issue of errors in genetic data sets is of growing concern, particularly in population genetics where whole genome mtDNA sequence data is coming under increased scrutiny. Multiplexed PCR reactions, combined with SNP typing, are currently under-exploited in this context, but have the potential to genotype whole populations rapidly and accurately, significantly reducing the amount of errors appearing in published data sets. To show the sensitivity of this technique for screening mtDNA genomic sequence data, 20 historic samples of the enigmatic Andaman Islanders and 12 modern samples from three Indian tribal populations (Chenchu, Lambadi and Lodha) were genotyped for 20 coding region sites after provisional haplogroup assignment with control region sequences.

No evidence for an mtDNA role in sperm motility: data from complete sequencing of asthenozoospermic males.

The first complete mitochondrial DNA (mtDNA) sequences (approximately 16,569 bp) in 20 patients with asthenozoospermia and a comparison with 23 new complete mtDNA sequences in teratoasthenozoospermic individuals, confirmed no sharing of specific polymorphisms or specific mitochondrial lineages between these individuals. This is strong evidence against the accepted claim of a major role played by mtDNA in male fertility, once supported by haplogroup association studies based on the screening of hypervariable region I. The hypothesis of maternally driven selection acting in male reproductive success must thus be treated with caution.

A mitochondrial stratigraphy for island southeast Asia.

Island Southeast Asia (ISEA) was first colonized by modern humans at least 45,000 years ago, but the extent to which the modern inhabitants trace their ancestry to the first settlers is a matter of debate. It is widely held, in both archaeology and linguistics, that they are largely descended from a second wave of dispersal, proto-Austronesian-speaking agriculturalists who originated in China and spread to Taiwan approximately 5,500 years ago. From there, they are thought to have dispersed into ISEA approximately 4,000 years ago, assimilating the indigenous populations.

Phylogeography and ethnogenesis of aboriginal Southeast Asians.

Studying the genetic history of the Orang Asli of Peninsular Malaysia can provide crucial clues to the peopling of Southeast Asia as a whole. We have analyzed mitochondrial DNA (mtDNAs) control-region and coding-region markers in 447 mtDNAs from the region, including 260 Orang Asli, representative of each of the traditional groupings, the Semang, the Senoi, and the Aboriginal Malays, allowing us to test hypotheses about their origins. All of the Orang Asli groups have undergone high levels of genetic drift, but phylogeographic traces nevertheless remain of the ancestry of their maternal lineages.

Harvesting the fruit of the human mtDNA tree.

Human mitochondrial DNA (mtDNA) studies have entered a new phase since the blossoming of complete genome analyses. Sequencing complete mtDNAs is more expensive and more labour intensive than restriction analysis or simply sequencing the control region of the molecule. But the efforts are paying off, as the phylogenetic resolution of the mtDNA tree has been greatly improved, and, in turn, phylogeographic interpretations can be given correspondingly greater precision in terms of the timing and direction of human dispersals.

A critical reassessment of the role of mitochondria in tumorigenesis.

Background: Mitochondrial DNA (mtDNA) is being analyzed by an increasing number of laboratories in order to investigate its potential role as an active marker of tumorigenesis in various types of cancer. Here we question the conclusions drawn in most of these investigations, especially those published in high-rank cancer research journals, under the evidence that a significant number of these medical mtDNA studies are based on obviously flawed sequencing results.

Methods And Findings: In our analyses, we take a phylogenetic approach and employ thorough database searches, which together have proven successful for detecting erroneous sequences in the fields of human population genetics and forensics.

Charting the ancestry of African Americans.

The Atlantic slave trade promoted by West European empires (15th-19th centuries) forcibly moved at least 11 million people from Africa, including about one-third from west-central Africa, to European and American destinations. The mitochondrial DNA (mtDNA) genome has retained an imprint of this process, but previous analyses lacked west-central African data. Here, we make use of an African database of 4,860 mtDNAs, which include 948 mtDNA sequences from west-central Africa and a further 154 from the southwest, and compare these for the first time with a publicly available database of 1,148 African Americans from the United States that contains 1,053 mtDNAs of sub-Saharan ancestry.