I am a scientist specialized in genetics and I currently study the peopling of the Americas.
Our DNA tells the story of our species, how we colonized the globe and our relation to pathologies.
In 10 seconds? On top of genetic information, our DNA contains important information about the history and evolution of our species, and it has allowed us to study our African origin, when and how we colonized continents and regions, ethnic predisposition to disease and even the relationship we had with other human species.
Don’t believe it? Recent advances in DNA sequencing technologies have made it easier and cheaper to sequence whole genomes, giving scientists huge amounts of information which has facilitated several breakthroughs in our understanding of human evolution, early global migrations, history and disease.
What do we know about human migrations? Thanks to our DNA we now know that we all come from eastern Africa, where groups of Homo sapiens diverged around 100,000 years ago, some groups migrated out of Africa, as early as 75,000 years ago, and colonized the entire globe: Australia 50,000 years ago; Europe 45,000 years ago; Arctic Siberia between 35,000 and 45,000 years ago; North America 15,000 years ago; and finally South America, one thousand years later. These migrations were shaped by global climate, sea level and glaciations, which opened or closed passages, allowing migration or isolating human groups.
And what about predisposition to disease? As humans migrated mutations accumulated in their DNA differently, so that today’s Asian, European, African or Amerindian communities have specific variants that they do not share with other ethnicities. These mutations may facilitate the appearance of certain diseases depending on our genetic background, like obesity, multiple sclerosis, cardiomyopathies or certain types of cancer.
What else have we learned? DNA has told us other interesting stuff, such as when and where did farming developed; the interactions of different human groups, either for love or war; and even that part of our DNA comes from other species, like from Neanderthals in Eurasians.
Abstract: Genetic variation on the Y chromosome has not been convincingly implicated in prostate cancer risk. To comprehensively analyze the role of inherited Y chromosome variation in prostate cancer risk in individuals of European ancestry, we genotyped 34 binary Y chromosome markers in 3,995 prostate cancer cases and 3,815 control subjects drawn from four studies. In this set, we identified nominally significant association between a rare haplogroup, E1b1b1c, and prostate cancer in stage I (P = 0.012, OR = 0.51; 95% confidence interval 0.30-0.87). Population substructure of E1b1b1c carriers suggested Ashkenazi Jewish ancestry, prompting a replication phase in individuals of both European and Ashkenazi Jewish ancestry. The association was not significant for prostate cancer overall in studies of either Ashkenazi Jewish (1,686 cases and 1,597 control subjects) or European (686 cases and 734 control subjects) ancestry (P(meta) = 0.078), but a meta-analysis of stage I and II studies revealed a nominally significant association with prostate cancer risk (P(meta) = 0.010, OR = 0.77; 95% confidence interval 0.62-0.94). Comparing haplogroup frequencies between studies, we noted strong similarities between those conducted in the US and France, in which the majority of men carried R1 haplogroups, resembling Northwestern European populations. On the other hand, Finns had a remarkably different haplogroup distribution with a preponderance of N1c and I1 haplogroups. In summary, our results suggest that inherited Y chromosome variation plays a limited role in prostate cancer etiology in European populations but warrant follow-up in additional large and well characterized studies of multiple ethnic backgrounds.
Pub.: 25 Jan '12, Pinned: 07 May '17
Abstract: Since mitochondria are the principal source of reactive oxygen species (ROS), these organelles may play an important role in ischemic cardiomyopathy (IC) development. The mitochondrial genome may influence this disease. The aim of the present study was to test the relationship between IC development and the impact of single nucleotide polymorphisms (SNPs) in mitochondrial DNA (mtDNA) defining the mitochondrial haplogroups in a population study.Ten major European haplogroups were identified by using the single base extension technique and by polymerase chain reaction-restriction fragment length polymorphism. Frequencies and Odds Ratios for the association between IC patients (n = 358) and healthy controls (n = 423) were calculated. No convincing associations between classical risk factors for ischemic cardiomyopathy development and haplogroups were found. However, compared to healthy controls, the prevalence of haplogroup H was significantly higher in IC patients (40.0% vs 50.0%, p-value = 0.039) while the frequency of haplogroup J was significantly lower (11.1% vs 5.6%, p-value = 0.048). The analysis of the SNPs characterizing the European mtDNA haplogroups showed that the m.7028C allele (40.0% vs 50.0%, p-value = 0.005) and m.14766C allele (43.0% vs 54.2%, p-value = 0.002) were overrepresented in IC patients, meanwhile the m.10398G allele (19.8% vs 13.1%, p-value = 0.015) and m.4216C allele (22.2% vs 16.5%, p-value = 0.044) were found as protective factors against IC.Our results showed that the haplogroups H and J were found as a risk and protective factors for ischemic cardiomyopathy development, respectively.
Pub.: 01 Sep '12, Pinned: 07 May '17
Abstract: The geographic origins of populations can be identified by their maternally inherited mitochondrial DNA (mtDNA) haplogroups. This study compared human cybrids (cytoplasmic hybrids), which are cell lines with identical nuclei but mitochondria from different individuals with mtDNA from either the H haplogroup or L haplogroup backgrounds. The most common European haplogroup is H while individuals of maternal African origin are of the L haplogroup. Despite lower mtDNA copy numbers, L cybrids had higher expression levels for nine mtDNA-encoded respiratory complex genes, decreased ATP (adenosine triphosphate) turnover rates and lower levels of reactive oxygen species production, parameters which are consistent with more efficient oxidative phosphorylation. Surprisingly, GeneChip arrays showed that the L and H cybrids had major differences in expression of genes of the canonical complement system (5 genes), dermatan/chondroitin sulfate biosynthesis (5 genes) and CCR3 (chemokine, CC motif, receptor 3) signaling (9 genes). Quantitative nuclear gene expression studies confirmed that L cybrids had (a) lower expression levels of complement pathway and innate immunity genes and (b) increased levels of inflammation-related signaling genes, which are critical in human diseases. Our data support the hypothesis that mtDNA haplogroups representing populations from different geographic origins may play a role in differential susceptibilities to diseases.
Pub.: 10 Nov '13, Pinned: 07 May '17
Abstract: To assess the influence of common mitochondrial DNA (mtDNA) sequence variation on multiple sclerosis (MS) risk in cases and controls part of an international consortium.We analyzed 115 high-quality mtDNA variants and common haplogroups from a previously published genome-wide association study among 7,391 cases from the International Multiple Sclerosis Genetics Consortium and 14,568 controls from the Wellcome Trust Case Control Consortium 2 project from 7 countries. Significant single nucleotide polymorphism and haplogroup associations were replicated in 3,720 cases and 879 controls from the University of California, San Francisco.An elevated risk of MS was detected among haplogroup JT carriers from 7 pooled clinic sites (odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.07-1.24, p = 0.0002) included in the discovery study. The increased risk of MS was observed for both haplogroup T (OR = 1.17, 95% CI = 1.06-1.29, p = 0.002) and haplogroup J carriers (OR = 1.11, 95% CI = 1.01-1.22, p = 0.03). These haplogroup associations with MS were not replicated in the independent sample set. An elevated risk of primary progressive (PP) MS was detected for haplogroup J participants from 3 European discovery populations (OR = 1.49, 95% CI = 1.10-2.01, p = 0.009). This elevated risk was borderline significant in the US replication population (OR = 1.43, 95% CI = 0.99-2.08, p = 0.058) and remained significant in pooled analysis of discovery and replication studies (OR = 1.43, 95% CI = 1.14-1.81, p = 0.002). No common individual mtDNA variants were associated with MS risk.Identification and validation of mitochondrial genetic variants associated with MS and PPMS may lead to new targets for treatment and diagnostic tests for identifying potential responders to interventions that target mitochondria.
Pub.: 03 Jul '15, Pinned: 07 May '17
Abstract: Aboriginal Australians represent one of the longest continuous cultural complexes known. Archaeological evidence indicates that Australia and New Guinea were initially settled approximately 50 thousand years ago (ka); however, little is known about the processes underlying the enormous linguistic and phenotypic diversity within Australia. Here we report 111 mitochondrial genomes (mitogenomes) from historical Aboriginal Australian hair samples, whose origins enable us to reconstruct Australian phylogeographic history before European settlement. Marked geographic patterns and deep splits across the major mitochondrial haplogroups imply that the settlement of Australia comprised a single, rapid migration along the east and west coasts that reached southern Australia by 49-45 ka. After continent-wide colonization, strong regional patterns developed and these have survived despite substantial climatic and cultural change during the late Pleistocene and Holocene epochs. Remarkably, we find evidence for the continuous presence of populations in discrete geographic areas dating back to around 50 ka, in agreement with the notable Aboriginal Australian cultural attachment to their country.
Pub.: 09 Mar '17, Pinned: 05 May '17
Abstract: Advances in the sequencing and the analysis of the genomes of both modern and ancient peoples have facilitated a number of breakthroughs in our understanding of human evolutionary history. These include the discovery of interbreeding between anatomically modern humans and extinct hominins; the development of an increasingly detailed description of the complex dispersal of modern humans out of Africa and their population expansion worldwide; and the characterization of many of the genetic adaptions of humans to local environmental conditions. Our interpretation of the evolutionary history and adaptation of humans is being transformed by analyses of these new genomic data.
Pub.: 20 Jan '17, Pinned: 05 May '17
Abstract: Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.
Pub.: 21 Sep '16, Pinned: 05 May '17
Abstract: High-coverage whole-genome sequence studies have so far focused on a limited number1 of geographically restricted populations2, 3, 4, 5, or been targeted at specific diseases, such as cancer6. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history7, 8, 9 and refuelled the debate on the mutation rate in humans10. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record11, and admixture between AMHs and Neanderthals predating the main Eurasian expansion12, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.
Pub.: 21 Sep '16, Pinned: 05 May '17
Abstract: We sequenced Early Neolithic genomes from the Zagros region of Iran (eastern Fertile Crescent), where some of the earliest evidence for farming is found, and identify a previously uncharacterized population that is neither ancestral to the first European farmers nor has contributed significantly to the ancestry of modern Europeans. These people are estimated to have separated from Early Neolithic farmers in Anatolia some 46-77,000 years ago and show affinities to modern day Pakistani and Afghan populations, but particularly to Iranian Zoroastrians. We conclude that multiple, genetically differentiated hunter-gatherer populations adopted farming in SW-Asia, that components of pre-Neolithic population structure were preserved as farming spread into neighboring regions, and that the Zagros region was the cradle of eastward expansion.
Pub.: 16 Jul '16, Pinned: 05 May '17
Abstract: Modern humans arrived in Europe ~45,000 years ago, but little is known about their genetic composition before the start of farming ~8,500 years ago. Here we analyse genome-wide data from 51 Eurasians from ~45,000-7,000 years ago. Over this time, the proportion of Neanderthal DNA decreased from 3-6% to around 2%, consistent with natural selection against Neanderthal variants in modern humans. Whereas there is no evidence of the earliest modern humans in Europe contributing to the genetic composition of present-day Europeans, all individuals between ~37,000 and ~14,000 years ago descended from a single founder population which forms part of the ancestry of present-day Europeans. An ~35,000-year-old individual from northwest Europe represents an early branch of this founder population which was then displaced across a broad region, before reappearing in southwest Europe at the height of the last Ice Age ~19,000 years ago. During the major warming period after ~14,000 years ago, a genetic component related to present-day Near Easterners became widespread in Europe. These results document how population turnover and migration have been recurring themes of European prehistory.
Pub.: 03 May '16, Pinned: 05 May '17
Abstract: As the last habitable continent colonized by humans, the site of multiple domestication hotspots, and the location of the largest Pleistocene megafaunal extinction, South America is central to human prehistory1, 2, 3, 4, 5, 6, 7. Yet remarkably little is known about human population dynamics during colonization, subsequent expansions, and domestication2, 3, 4, 5. Here we reconstruct the spatiotemporal patterns of human population growth in South America using a newly aggregated database of 1,147 archaeological sites and 5,464 calibrated radiocarbon dates spanning fourteen thousand to two thousand years ago (ka). We demonstrate that, rather than a steady exponential expansion, the demographic history of South Americans is characterized by two distinct phases. First, humans spread rapidly throughout the continent, but remained at low population sizes for 8,000 years, including a 4,000-year period of ‘boom-and-bust’ oscillations with no net growth. Supplementation of hunting with domesticated crops and animals4, 8 had a minimal impact on population carrying capacity. Only with widespread sedentism, beginning ~5 ka4, 8, did a second demographic phase begin, with evidence for exponential population growth in cultural hotspots, characteristic of the Neolithic transition worldwide9. The unique extent of humanity’s ability to modify its environment to markedly increase carrying capacity in South America is therefore an unexpectedly recent phenomenon.
Pub.: 06 Apr '16, Pinned: 05 May '17
Abstract: Archaeological evidence for human dispersal through northern Eurasia before 40,000 years ago is rare. In west Siberia, the northernmost find of that age is located at 57°N. Elsewhere, the earliest presence of humans in the Arctic is commonly thought to be circa 35,000 to 30,000 years before the present. A mammoth kill site in the central Siberian Arctic, dated to 45,000 years before the present, expands the populated area to almost 72°N. The advancement of mammoth hunting probably allowed people to survive and spread widely across northernmost Arctic Siberia.
Pub.: 28 Jan '16, Pinned: 05 May '17
Abstract: To determine whether a specific mitochondrial DNA (mtDNA) haplogroup is implicated in the pathogenesis of intrauterine adhesion (IUA).Peripheral blood samples were collected from 486 women with (case group, n = 154) and without IUA (control group, n = 332) at the Women's Hospital, Zhejiang University School of Medicine. Genomic DNA was extracted from the blood, and the mtDNA haplogroups of Han women M, N and R were determined by sequencing hypervariable mtDNA segments and testing diagnostic polymorphisms in the mtDNA coding region.Women with mtDNA haplogroup R had an independently increased genetic risk factor for IUA with an OR 1.77 (95% CI 1.16-2.70, p = 0.009) compared with women without. Moreover, repeated intrauterine surgery within 1 month and number of intrauterine operations were both significantly associated with IUA (p < 0.001).These results suggest that mtDNA haplogroup R, one of the main mtDNA haplogroups in Han population, is a strong independent genetic risk factor for women with IUA.
Pub.: 16 Oct '15, Pinned: 05 May '17