Paolo Anagnostou

The peopling of Europe and the cautionary tale of Y chromosome lineage R-M269

Recently, the debate on the origins of the major European Y chromosome haplogroup R1b1b2-M269 has reignited, and opinion has moved away from Palaeolithic origins to the notion of a younger Neolithic spread of these chromosomes from the Near East. Here, we address this debate by investigating frequency patterns and diversity in the largest collection of R1b1b2-M269 chromosomes yet assembled. Our analysis reveals no geographical trends in diversity, in contradiction to expectation under the Neolithic hypothesis, and suggests an alternative explanation for the apparent cline in diversity recently described. We further investigate the young, STR-based time to the most recent common ancestor estimates proposed so far for R-M269-related lineages and find evidence for an appreciable effect of microsatellite choice on age estimates. As a consequence, the existing data and tools are insufficient to make credible estimates for the age of this haplogroup, and conclusions about the timing of its origin and dispersal should be viewed with a large degree of caution.

Genetic Origins of Lactase Persistence and the Spread of Pastoralism in Africa

In humans, the ability to digest lactose, the sugar in milk, declines after weaning because of decreasing levels of the enzyme lactase-phlorizin hydrolase, encoded by LCT. However, some individuals maintain high enzyme amounts and are able to digest lactose into adulthood (i.e., they have the lactase-persistence [LP] trait). It is thought that selection has played a major role in maintaining this genetically determined phenotypic trait in different human populations that practice pastoralism. To identify variants associated with the LP trait and to study its evolutionary history in Africa, we sequenced MCM6 introns 9 and 13 and ~2 kb of the LCT promoter region in 819 individuals from 63 African populations and in 154 non-Africans from nine populations. We also genotyped four microsatellites in an ~198 kb region in a subset of 252 individuals to reconstruct the origin and spread of LP-associated variants in Africa. Additionally, we examined the association between LP and genetic variability at candidate regulatory regions in 513 individuals from eastern Africa. Our analyses confirmed the association between the LP trait and three common variants in intron 13 (C-14010, G-13907, and G-13915). Furthermore, we identified two additional LP-associated SNPs in intron 13 and the promoter region (G-12962 and T-956, respectively). Using neutrality tests based on the allele frequency spectrum and long-range linkage disequilibrium, we detected strong signatures of recent positive selection in eastern African populations and the Fulani from central Africa. In addition, haplotype analysis supported an eastern African origin of the C-14010 LP-associated mutation in southern Africa.

Mine, Yours, Ours? Sharing Data on Human Genetic Variation

The achievement of a robust, effective and responsible form of data sharing is currently regarded as a priority for biological and bio-medical research. Empirical evaluations of data sharing may be regarded as an indispensable first step in the identification of critical aspects and the development of strategies aimed at increasing availability of research data for the scientific community as a whole. Research concerning human genetic variation represents a potential forerunner in the establishment of widespread sharing of primary datasets. However, no specific analysis has been conducted to date in order to ascertain whether the sharing of primary datasets is common-practice in this research field. To this aim, we analyzed a total of 543 mitochondrial and Y chromosomal datasets reported in 508 papers indexed in the Pubmed database from 2008 to 2011. A substantial portion of datasets (21.9%) was found to have been withheld, while neither strong editorial policies nor high impact factor proved to be effective in increasing the sharing rate beyond the current figure of 80.5%. Disaggregating datasets for research fields, we could observe a substantially lower sharing in medical than evolutionary and forensic genetics, more evident for whole mtDNA sequences (15.0% vs 99.6%). The low rate of positive responses to e-mail requests sent to corresponding authors of withheld datasets (28.6%) suggests that sharing should be regarded as a prerequisite for final paper acceptance, while making authors deposit their results in open online databases which provide data quality control seems to provide the best-practice standard. Finally, we estimated that 29.8% to 32.9% of total resources are used to generate withheld datasets, implying that an important portion of research funding does not produce shared knowledge. By making the scientific community and the public aware of this important aspect, we may help popularize a more effective culture of data sharing.

Tracing the distribution and evolution of lactase persistence in Southern Europe through the study of the T(-13910) variant.

We investigated the occurrence and intra‐allelic variability of the T‐13910 variant located upstream of the lactase gene in 965 individuals from 20 different locations of Italy and Greece. The T‐13910 frequency ranges from 0.072 (Sardinia) to 0.237 (North‐East Italy), with a statistically significant difference between North‐East Italians and other Italian populations. The comparison of the lactose tolerance predicted by T‐13910 and that assessed by other studies using physiological tests shows a one‐way statistically significant discrepancy that could be due to sampling differences. However, the possible role of other genetic factors underlying lactase persistence is worth exploring. The time of the most recent common ancestor and departures from neutrality of the T‐13910 allele were assessed using three microsatellite loci. Time estimates were found to be congruent with the appearance of dairy farming in Southern Europe and the occurrence of a single introgression event. Robust signals of selection can be observed in North‐East Italy only. We discuss the possible role of cultural traits and genetic history in determining these observed micro‐evolutionary patterns. Am. J. Hum. Biol. 2009.

The Role of Recent Admixture in Forming the Contemporary West Eurasian Genomic Landscape

Over the past few years, studies of DNA isolated from human fossils and archaeological remains have generated considerable novel insight into the history of our species. Several landmark papers have described the genomes of ancient humans across West Eurasia, demonstrating the presence of large-scale, dynamic population movements over the last 10,000 years, such that ancestry across present-day populations is likely to be a mixture of several ancient groups [1-7]. While these efforts are bringing the details of West Eurasian prehistory into increasing focus, studies aimed at understanding the processes behind the generation of the current West Eurasian genetic landscape have been limited by the number of populations sampled or have been either too regional or global in their outlook [8-11]. Here, using recently described haplotype-based techniques [11], we present the results of a systematic survey of recent admixture history across Western Eurasia and show that admixture is a universal property across almost all groups. Admixture in all regions except North Western Europe involved the influx of genetic material from outside of West Eurasia, which we date to specific time periods. Within Northern, Western, and Central Europe, admixture tended to occur between local groups during the period 300 to 1200 CE. Comparisons of the genetic profiles of West Eurasians before and after admixture show that population movements within the last 1,500 years are likely to have maintained differentiation among groups. Our analysis provides a timeline of the gene flow events that have generated the contemporary genetic landscape of West Eurasia.Summary Over the past few years, studies of DNA isolated from human fossils and archaeological remains have generated considerable novel insight into the history of our species. Several landmark papers have described the genomes of ancient humans across West Eurasia, demonstrating the presence of large-scale, dynamic population movements over the last 10,000 years, such that ancestry across present-day populations is likely to be a mixture of several ancient groups [1, 2, 3, 4, 5, 6, 7]. While these efforts are bringing the details of West Eurasian prehistory into increasing focus, studies aimed at understanding the processes behind the generation of the current West Eurasian genetic landscape have been limited by the number of populations sampled or have been either too regional or global in their outlook [8, 9, 10, 11]. Here, using recently described haplotype-based techniques [11], we present the results of a systematic survey of recent admixture history across Western Eurasia and show that admixture is a universal property across almost all groups. Admixture in all regions except North Western Europe involved the influx of genetic material from outside of West Eurasia, which we date to specific time periods. Within Northern, Western, and Central Europe, admixture tended to occur between local groups during the period 300 to 1200 CE. Comparisons of the genetic profiles of West Eurasians before and after admixture show that population movements within the last 1,500 years are likely to have maintained differentiation among groups. Our analysis provides a timeline of the gene flow events that have generated the contemporary genetic landscape of West Eurasia.

Online databases for mtDNA and Y chromosome polymorphisms in human populations

This study presents an overview of online databases for mtDNA and Y chromosome polymorphisms in human populations. In order to provide readers with information which may help optimize their use, we focus on: (i) type, quantity and source of data contained; (ii) possibilities of downloading and uploading; (iii) availability of data filters and population genetics tools. We show that some of these databases offer a useful complement to the primary databases by giving access to additional data and making it possible to perform queries which exploit some specific metadata. Thereafter, we evaluate the state of the art from an evolutionary anthropologists point of view. We suggest that online databases could become even more useful research tools by combining an easier data retrieval with quality control and by making a more extensive use of metadata regarding populations and individuals. Making population data on mtDNA and Y chromosome polymorphisms more complete, well ordered and easily accessible, we could better exploit the potential of new generation sequencing techniques for advancements in human evolutionary genetics.

Detecting Genetic Isolation in Human Populations: A Study of European Language Minorities

The identification of isolation signatures is fundamental to better understand the genetic structure of human populations and to test the relations between cultural factors and genetic variation. However, with current approaches, it is not possible to distinguish between the consequences of long-term isolation and the effects of reduced sample size, selection and differential gene flow. To overcome these limitations, we have integrated the analysis of classical genetic diversity measures with a Bayesian method to estimate gene flow and have carried out simulations based on the coalescent. Combining these approaches, we first tested whether the relatively short history of cultural and geographical isolation of four “linguistic islands” of the Eastern Alps (Lessinia, Sauris, Sappada and Timau) had left detectable signatures in their genetic structure. We then compared our findings to previous studies of European population isolates. Finally, we explored the importance of demographic and cultural factors in shaping genetic diversity among the groups under study. A combination of small initial effective size and continued genetic isolation from surrounding populations seems to provide a coherent explanation for the diversity observed among Sauris, Sappada and Timau, which was found to be substantially greater than in other groups of European isolated populations. Simulations of micro-evolutionary scenarios indicate that ethnicity might have been important in increasing genetic diversity among these culturally related and spatially close populations.

Research data sharing: Lessons from forensic genetics.

Abstract In this study, we present an empirical assessment of the extent and way in which data are shared in forensic genetic papers. The analysis is based on the scrutiny of datasets published between 2008 and 2011. The elevated sharing rate of forensic genetic datasets (86.06%), is discussed in relation to: (i) the editorial policies of the two main journals in the field (Forensic Science International: Genetics and International Journal of Legal Medicine); (ii) the cooperative efforts to develop common standards and achieve full reproducibility of genotyping techniques in the forensic genetic community.

The Greeks in the West: genetic signatures of the Hellenic colonisation in southern Italy and Sicily

Greek colonisation of South Italy and Sicily (Magna Graecia) was a defining event in European cultural history, although the demographic processes and genetic impacts involved have not been systematically investigated. Here, we combine high-resolution surveys of the variability at the uni-parentally inherited Y chromosome and mitochondrial DNA in selected samples of putative source and recipient populations with forward-in-time simulations of alternative demographic models to detect signatures of that impact. Using a subset of haplotypes chosen to represent historical sources, we recover a clear signature of Greek ancestry in East Sicily compatible with the settlement from Euboea during the Archaic Period (eighth to fifth century BCE). We inferred moderate sex-bias in the numbers of individuals involved in the colonisation: a few thousand breeding men and a few hundred breeding women were the estimated number of migrants. Last, we demonstrate that studies aimed at quantifying Hellenic genetic flow by the proportion of specific lineages surviving in present-day populations may be misleading.

When data sharing gets close to 100%: what human paleogenetics can teach the Open Science movement

This study analyzes data sharing regarding mitochondrial, Y chromosomal and autosomal polymorphisms in a total of 162 papers on ancient human DNA published between 1988 and 2013. The estimated sharing rate was not far from totality (97.6% ± 2.1%) and substantially higher than observed in other fields of genetic research (evolutionary, medical and forensic genetics). Both a questionnaire-based survey and the examination of Journals’ editorial policies suggest that this high sharing rate cannot be simply explained by the need to comply with stakeholders requests. Most data were made available through body text, but the use of primary databases increased in coincidence with the introduction of complete mitochondrial and next-generation sequencing methods. Our study highlights three important aspects. First, our results imply that researchers’ awareness of the importance of openness and transparency for scientific progress may complement stakeholders’ policies in achieving very high sharing rates. Second, widespread data sharing does not necessarily coincide with a prevalent use of practices which maximize data findability, accessibility, useability and preservation. A detailed look at the different ways in which data are released can be very useful to detect failures to adopt the best sharing modalities and understand how to correct them. Third and finally, the case of human paleogenetics tells us that a widespread awareness of the importance of Open Science may be important to build reliable scientific practices even in the presence of complex experimental challenges.