RICERCA ITALIANA     

The peopling of the European continent: the mitochondrial DNA and Y chromosome perspectives

Università degli Studi di Pavia

Abstract

It has been recently suggested that global colonization by the human species is one of the “big questions” in human origins for both biological and non-biological disciplines. This project focuses its attention on the peopling of Europe - applying modern genetic methods to address this issue in finer detail than has ever before been possible. We will evaluate the sequence variation in the male-specific region of the Y chromosome (MSY) and the maternally-inherited mitochondrial DNA (mtDNA) - the only non-recombining genetic systems in humans - in order to unravel which aspects of contemporary human genetic variation in Europe are the result of primary colonization, late-glacial expansions from Ice-Age refugia, Neolithic dispersals or more recent events of gene flow. To achieve this objective we are going to utilize the sequence information contained in six mtDNA haplogroups (J1, J2, T1, T2, U3 and U7) and most European Y-chromosome haplogroups taking advantage of two major progresses in phylogeographic studies: (i) the possibility of carrying out human mtDNA studies at the highest level of molecular resolution - the sequencing of entire mitochondrial genomes - and (ii) the recent advances in mutation-detection technology allowing both a “relatively easy” search and a systematic survey at the population level of high-resolution markers (SNPs) on the MSY.

The project is complex but will be carried in the context of a long-standing collaboration among five >>>

Principal Investigator

Antonio Torroni Università degli Studi di PAVIA

Research Objectives

Our objective is to determine which aspects of contemporary human genetic variation in Europe are due to primary colonization, late-glacial expansions from Ice-Age refugia, Neolithic dispersals or more recent events of gene flow. To achieve this objective we are going to utilize the sequence information contained in six mtDNA haplogroups (J1, J2, T1, T2, U3 and U7) and most European Y-chromosome haplogroups taking advantage of two recent major progresses in phylogeographic studies:

(1) Complete mtDNA sequencing has led to a greatly improved resolution of the maternal genealogy. Although complete sequencing is still expensive and time-consuming, the information from even a relatively limited complete-sequence database can be exploited to design high-resolution typing systems that focus on specific branches in the tree. For instance in the study of Olivieri et al. (2006), by sequencing only 81 entire mtDNAs, we were able to identify all of the informative markers of haplogroups M1 and U6 and their internal clades. This was followed by a large-scale screening of M1 and U6 mtDNAs from the entire distribution range of the two haplogroups, which demonstrated that after the “Out of Africa” exit – ~70,000 years ago– of modern humans through a “southern dispersal route” (Macaulay et al. 2005), a subsequent dispersal event from the Levant led to the peopling of both Europe and North Africa about 40-45,000 years ago.

(2) The identification of >>>

First Results

The added values of this research refer to both advancements in genetics (intrinsic value) and in interdisciplinarity (extrinsic value).

Intrinsically, this research will represent a leap forward in the description and comprehension of the genetic landscape of Europe. This achievement has been pursued since many decades, and the level of knowledge has been growing in parallel with theoretical and methodological developments. The main aim is to arrive at a "picture" of an entire "genetic pool" and to reconstruct the events that led to its present composition. Uniparental DNA markers (mtDNA and MSY) are here used to highlight features shared by the whole continent but also to spot specificities for some geographical regions or populations. From the genetic point of view, these data are important to draw inferences on particular regional gene pools, in which some autosomal variants may reach epidemiological relevance (e.g. lactase deficiency in the Baltic area). Furthermore, advancements in the methodologies must be considered. These refer to the best resequencing strategies, and the most reliable analyses for dating and phylogeographic inferences.

Moreover, the mtDNA and the MSY are not simply two pieces of DNA with peculiar features, informative for evolutionary studies. They contain genes with important functions and their sequence variation has been associated to a wide range of complex diseases / phenotypes (as for mtDNA >>>

Timescale

24 months

National and international background

Anatomically and behaviorally modern humans entered Europe from the Levant and rapidly dispersed into the continent between 46,000 and 41,000 years ago (Mellars 2006). This is considered to be the seeding event in the formation of the gene pool of modern Europeans. The rapid spread into Europe was probably facilitated by a major improvement in climatic conditions between about 43-41,000 years ago (the period of the Hengelo interstadial), which would inevitably have made a process of population expansion from southeast to northwest across Europe easier to achieve (Shackleton et al. 2004; Mellars, 1996, 1998).

After the arrival of first hunters and gatherers, the genetic structure of Europeans has been influenced by two important events: the retreat of European populations into refugia during the Last Glacial Maximum (LGM) about 20,000 years ago, followed by re-expansions starting from about 13,000 years ago, and the Neolithic revolution about 8-10,000 years ago when the agriculture spread all over Europe from the Near East. More recent events of gene flow must be also taken into account when dealing with the complexity of the European genetic landscape. Most of those probably did not have a demographic impact at the continental level, but certainly played an important role in shaping the gene pool of specific regions of Europe.

There are two models to explain the spread of agriculture: the demic diffusion model assumes that the Neolithic >>>