Trends in Genetics
Volume 22, Issue 6, June 2006, Pages 339-345
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Harvesting the fruit of the human mtDNA tree

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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. Therefore, despite mtDNA being only a fraction of our total genome, the deciphering of its evolution is profoundly changing our perception about how modern humans spread across our planet. Here we illustrate the phylogeographic approach with two case studies: the initial dispersal out of Africa, and the colonization of Europe.

Introduction

In human cells, most genes (∼25 000) are confined to the nucleus, limited to two copies per cell and transmitted equally from both parents according to Mendel's laws. A major exception is represented by the 37 mitochondrial DNA (mtDNA) genes. They are located within the mitochondria, organized in a small (∼16.6 Kb) circular molecule of DNA, which is present in hundreds to thousands of copies per cell, and transmitted as a non-recombining unit only through the mother. Furthermore, human mtDNA is characterized by a much greater evolutionary rate than that of the average nuclear gene. Thus, its sequence variation has been generated solely by the sequential accumulation of new mutations along radiating maternal lineages. The time frame of these mutations is such that human mtDNA contains a molecular record not only of the genealogical history but also of the migrations of women who transmitted it through the generations. Because the process of molecular differentiation is relatively fast and occurred mainly during and after the recent process of dispersal into different parts of the world, subsets of mtDNA variation usually tend to be restricted to particular geographic areas and populations. Recent analyses of this variation at the highest possible level of molecular resolution (i.e. that of complete mtDNA sequences) are now enabling us to determine where and when particular branching events are likely to have occurred, as the first step in the reconstruction of prehistoric human dispersals.

Section snippets

Human mtDNA variation

The earliest mitochondrial DNA research began by digesting the entire molecule with just a few restriction enzymes. As early as 1980, Brown's pioneering study of 21 humans from diverse ethnic and geographic backgrounds indicated that mtDNA restriction-enzyme fragment length polymorphism (RFLP) patterns could be used to trace human genetic history [1]. On the basis of the observed diversity in a worldwide sample, he obtained a surprisingly recent coalescence age estimate of ∼180 000 years for

Archaeogenetics

Amorim [27] coined the elegant term ‘archaeogenetics’ for ‘the newly-emerged discipline that applies molecular genetics to the study of the human past’ [28], thus substituting the earlier term ‘historical genetics’ [29]. Archaeogenetics was prefigured in the work of Luca Cavalli-Sforza and his colleagues, working on classical genetic markers in the 1970s (see Ref. [30] for a personal account; and Ref. [31] for a summary of the classical work). Cavalli-Sforza's work was the first major attempt

Out of Africa

Travelling up the human mtDNA phylogeny from the root, corresponding to what has, often rather confusingly, been identified with ‘mitochondrial Eve’ [34], one passes through several bi- and trifurcations until one reaches the first multifurcation node, the root of haplogroup L3 (Figure 1). This root gave rise to many (successful) descendant haplogroups, perhaps reflecting some colonization event or local population growth ∼80 000–90 000 years ago, which might have been triggered by the glacial

Into Europe

Early mtDNA studies of European populations revealed that all Europeans essentially share the same set of haplogroups as Near Easterners and that those haplogroups were absent from sub-Saharan Africans and East Asians [39]. These observations confirmed that Europeans and Near Easterners share a rather recent common ancestry. From the complete mtDNA phylogeny that is now available, we can see that European mtDNA variation – embedded as it is in the West Eurasian mtDNA variation – is surprisingly

Perspective and concluding remarks

Mitochondrial DNA, along with DNA from the non-recombining portion of the Y chromosome, will be used more and more in elucidating human evolution and pioneer settlement patterns because, at least for the moment, autosomal genes lack the high resolution of the uniparental markers. A prerequisite for future progress is, however, the use of the information from the entire DNA molecule. There is still much work to be done to find all the polymorphic sites on the Y chromosome, but already the SNP

Acknowledgements

This research received support from The Royal Society, The British Academy, The Italian Ministry of the University (Fondo Investimenti Ricerca di Base 2001, Progetti Ricerca Interesse Nazionale 2005) and Fondazione Cariplo.

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