Anthropology, Population Genetics & Pharmacogenomics

Estella Poloni

Senior Lecturer

  • T: +41 22 379 69 77
  • office 4-416 (Sciences II)

My research main themes focus on the origin and evolution of genetic diversity in human populations, the structure of this diversity among them, and its links to the history of migrations and cultural differentiations (such as the history of languages). Since many years now, I have been investigating the diversity of human populations in sex-linked polymorphisms (mitochondrial DNA and Y chromosome) because of their potential to reveal distinct population histories of men and women, due for instance to differentiated degrees of genetic exchanges between populations. As such, I have developed a special interest in the diversity of populations at the crossroads between continents, particularly so in the regions surrounding the Mediterranean Sea, namely East and North Africa, West Asia and Southern Europe. I am also fascinated by the extreme cultural diversity of humans, which testifies to the ability of our ancestors to innovate and colonize all biotopes, and which has probably also left imprints in the current human genome, as attested by the phenotypic variability of our species. For this reason, my research focuses nowadays on the evolution of human variability in genomic regions likely targeted by selective pressures linked to the natural and cultural environments of populations, such as polymorphisms in drug metabolizing genes (NAT and CYP genes). I also investigate the variability of these genomic regions in our closest relatives, the chimpanzees, to understand the potential functional role of such polymorphisms.

Current FNS projects

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  • Human genomic population structure and phenotype-genotype variation in ADME genes along a latitudinal transect from Africa to Europe
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Bioinformatic platform

  • The historical spread of Arabian Pastoralists to the eastern African Sahel evidenced by the lactase persistence -13,915*G allele and mitochondrial DNA. Am. J. Hum. Biol. 2017 Jan;():. 10.1002/ajhb.22950.

    abstract

    Thanks to the ability to digest lactose, Arabian nomads had become less dependent upon their sedentary neighbors and some of these populations spread to Africa. When and by which route they migrated to their current locations have previously been addressed only by historical and archaeological data.

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  • Comprehensive view of the population history of Arabia as inferred by mtDNA variation. Am. J. Phys. Anthropol. 2016 Apr;159(4):607-16. 10.1002/ajpa.22920.

    abstract

    Genetic and archaeological research supports the theory that Arabia was the first region traversed by modern humans as they left Africa and dispersed throughout Eurasia. However, the role of Arabia from the initial migration out of Africa until more recent times is still unclear.

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  • Variation in NAT2 acetylation phenotypes is associated with differences in food-producing subsistence modes and ecoregions in Africa. BMC Evol. Biol. 2015 ;15():263. 10.1186/s12862-015-0543-6. 10.1186/s12862-015-0543-6. PMC4665893.

    abstract

    Dietary changes associated to shifts in subsistence strategies during human evolution may have induced new selective pressures on phenotypes, as currently held for lactase persistence. Similar hypotheses exist for arylamine N-acetyltransferase 2 (NAT2) mediated acetylation capacity, a well-known pharmacogenetic trait with wide inter-individual variation explained by polymorphisms in the NAT2 gene. The environmental causative factor (if any) driving its evolution is as yet unknown, but significant differences in prevalence of acetylation phenotypes are found between hunter-gatherer and food-producing populations, both in sub-Saharan Africa and worldwide, and between agriculturalists and pastoralists in Central Asia. These two subsistence strategies also prevail among sympatric populations of the African Sahel, but knowledge on NAT2 variation among African pastoral nomads was up to now very scarce. Here we addressed the hypothesis of different selective pressures associated to the agriculturalist or pastoralist lifestyles having acted on the evolution of NAT2 by sequencing the gene in 287 individuals from five pastoralist and one agriculturalist Sahelian populations.

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  • The place of Slovakian paternal diversity in the clinal European landscape. Ann. Hum. Biol. 2015 ;42(6):511-22. 10.3109/03014460.2014.974668.

    abstract

    Several demographic events have been postulated to explain the contemporaneous structure of European genetic diversity. First, an initial settlement of the continent by anatomically modern humans; second, the re-settlement of northern latitudes after the Last Glacial Maximum; third, the demic diffusion of Neolithic farmers from the Near East; and, fourth, several historical events such as the Slavic migration.

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  • Taiwan Y-chromosomal DNA variation and its relationship with Island Southeast Asia. BMC Genet. 2014 ;15():77. 1471-2156-15-77. 10.1186/1471-2156-15-77. PMC4083334.

    abstract

    Much of the data resolution of the haploid non-recombining Y chromosome (NRY) haplogroup O in East Asia are still rudimentary and could be an explanatory factor for current debates on the settlement history of Island Southeast Asia (ISEA). Here, 81 slowly evolving markers (mostly SNPs) and 17 Y-chromosomal short tandem repeats were used to achieve higher level molecular resolution. Our aim is to investigate if the distribution of NRY DNA variation in Taiwan and ISEA is consistent with a single pre-Neolithic expansion scenario from Southeast China to all ISEA, or if it better fits an expansion model from Taiwan (the OOT model), or whether a more complex history of settlement and dispersals throughout ISEA should be envisioned.

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  • Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons. Clin. Infect. Dis. 2013 Jul;57(1):112-21. cit196. 10.1093/cid/cit196. PMC3669528.

    abstract

    Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.

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  • Rapid birth-and-death evolution of the xenobiotic metabolizing NAT gene family in vertebrates with evidence of adaptive selection. BMC Evol. Biol. 2013 ;13():62. 1471-2148-13-62. 10.1186/1471-2148-13-62. PMC3601968.

    abstract

    The arylamine N-acetyltransferases (NATs) are a unique family of enzymes widely distributed in nature that play a crucial role in the detoxification of aromatic amine xenobiotics. Considering the temporal changes in the levels and toxicity of environmentally available chemicals, the metabolic function of NATs is likely to be under adaptive evolution to broaden or change substrate specificity over time, making NATs a promising subject for evolutionary analyses. In this study, we trace the molecular evolutionary history of the NAT gene family during the last ~450 million years of vertebrate evolution and define the likely role of gene duplication, gene conversion and positive selection in the evolutionary dynamics of this family.

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  • Human neutral genetic variation and forensic STR data. PLoS ONE 2012 ;7(11):e49666. 10.1371/journal.pone.0049666. PONE-D-12-16962. PMC3504113.

    abstract

    The forensic genetics field is generating extensive population data on polymorphism of short tandem repeats (STR) markers in globally distributed samples. In this study we explored and quantified the informative power of these datasets to address issues related to human evolution and diversity, by using two online resources: an allele frequency dataset representing 141 populations summing up to almost 26 thousand individuals; a genotype dataset consisting of 42 populations and more than 11 thousand individuals. We show that the genetic relationships between populations based on forensic STRs are best explained by geography, as observed when analysing other worldwide datasets generated specifically to study human diversity. However, the global level of genetic differentiation between populations (as measured by a fixation index) is about half the value estimated with those other datasets, which contain a much higher number of markers but much less individuals. We suggest that the main factor explaining this difference is an ascertainment bias in forensics data resulting from the choice of markers for individual identification. We show that this choice results in average low variance of heterozygosity across world regions, and hence in low differentiation among populations. Thus, the forensic genetic markers currently produced for the purpose of individual assignment and identification allow the detection of the patterns of neutral genetic structure that characterize the human population but they do underestimate the levels of this genetic structure compared to the datasets of STRs (or other kinds of markers) generated specifically to study the diversity of human populations.

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  • Arylamine N-acetyltransferase 2 (NAT2) genetic diversity and traditional subsistence: a worldwide population survey. PLoS ONE 2011 ;6(4):e18507. 10.1371/journal.pone.0018507. PMC3071824.

    abstract

    Arylamine N-acetyltransferase 2 (NAT2) is involved in human physiological responses to a variety of xenobiotic compounds, including common therapeutic drugs and exogenous chemicals present in the diet and the environment. Many questions remain about the evolutionary mechanisms that have led to the high prevalence of slow acetylators in the human species. Evidence from recent surveys of NAT2 gene variation suggests that NAT2 slow-causing variants might have become targets of positive selection as a consequence of the shift in modes of subsistence and lifestyle in human populations in the last 10,000 years. We aimed to test more extensively the hypothesis that slow acetylation prevalence in humans is related to the subsistence strategy adopted by the past populations. To this end, published frequency data on the most relevant genetic variants of NAT2 were collected from 128 population samples (14,679 individuals) representing different subsistence modes and dietary habits, allowing a thorough analysis at both a worldwide and continent scale. A significantly higher prevalence of the slow acetylation phenotype was observed in populations practicing farming (45.4%) and herding (48.2%) as compared to populations mostly relying on hunting and gathering (22.4%) (P = 0.0007). This was closely mirrored by the frequency of the slow 590A variant that was found to occur at a three-fold higher frequency in food producers (25%) as compared to hunter-gatherers (8%). These findings are consistent with the hypothesis that the Neolithic transition to subsistence economies based on agricultural and pastoral resources modified the selective regime affecting the NAT2 acetylation pathway. Furthermore, the vast amount of data collected enabled us to provide a comprehensive and up-to-date description of NAT2 worldwide genetic diversity, thus building up a useful resource of frequency data for further studies interested in epidemiological or anthropological research questions involving NAT2.

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  • No longitudinal mitochondrial DNA sequence changes in HIV-infected individuals with and without lipoatrophy. J. Infect. Dis. 2011 Mar;203(5):620-4. jiq106. 10.1093/infdis/jiq106. PMC3072732.

    abstract

    The potential for mitochondrial (mt) DNA mutation accumulation during antiretroviral therapy (ART), and preferential accumulation in patients with lipoatrophy compared with control participants, remains controversial. We sequenced the entire mitochondrial genome, both before ART and after ART exposure, in 29 human immunodeficiency virus (HIV)-infected Swiss HIV Cohort Study participants initiating a first-line thymidine analogue-containing ART regimen. No accumulation of mtDNA mutations or deletions was detected in 13 participants who developed lipoatrophy or in 16 control participants after significant and comparable ART exposure (median duration, 3.3 and 3.7 years, respectively). In HIV-infected persons, the development of lipoatrophy is unlikely to be associated with accumulation of mtDNA mutations detectable in peripheral blood.

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  • Human genetic differentiation across the Strait of Gibraltar. BMC Evol. Biol. 2010 ;10():237. 1471-2148-10-237. 10.1186/1471-2148-10-237. PMC3020631.

    abstract

    The Strait of Gibraltar is a crucial area in the settlement history of modern humans because it represents a possible connection between Africa and Europe. So far, genetic data were inconclusive about the fact that this strait constitutes a barrier to gene flow, as previous results were highly variable depending on the genetic locus studied. The present study evaluates the impact of the Gibraltar region in reducing gene flow between populations from North-Western Africa and South-Western Europe, by comparing formally various genetic loci. First, we compute several statistics of population differentiation. Then, we use an original simulation approach in order to infer the most probable evolutionary scenario for the settlement of the area, taking into account the effects of both demography and natural selection at some loci.

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  • Genetic evidence for complexity in ethnic differentiation and history in East Africa. Ann. Hum. Genet. 2009 Nov;73(Pt 6):582-600. AHG541. 10.1111/j.1469-1809.2009.00541.x.

    abstract

    The Afro-Asiatic and Nilo-Saharan language families come into contact in Western Ethiopia. Ethnic diversity is particularly high in the South, where the Nilo-Saharan Nyangatom and the Afro-Asiatic Daasanach dwell. Despite their linguistic differentiation, both populations rely on a similar agripastoralist mode of subsistence. Analysis of mitochondrial DNA extracted from Nyangatom and Daasanach archival sera revealed high levels of diversity, with most sequences belonging to the L haplogroups, the basal branches of the mitochondrial phylogeny. However, in sharp contrast with other Ethiopian populations, only 5% of the Nyangatom and Daasanach sequences belong to haplogroups M and N. The Nyangatom and Daasanach were found to be significantly differentiated, while each of them displays close affinities with some Tanzanian populations. The strong genetic structure found over East Africa was neither associated with geography nor with language, a result confirmed by the analysis of 6711 HVS-I sequences of 136 populations mainly from Africa. Processes of migration, language shift and group absorption are documented by linguists and ethnographers for the Nyangatom and Daasanach, thus pointing to the probably transient and plastic nature of these ethnic groups. These processes, associated with periods of isolation, could explain the high diversity and strong genetic structure found in East Africa.

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  • Local population structure in Arabian Peninsula revealed by Y-STR diversity. Hum. Hered. 2009 ;68(1):45-54. 000210448. 10.1159/000210448.

    abstract

    Genetic studies have been underway on Arabian Peninsula populations because of their pivotal geographic location for population migration and times of occurrence. To assist in better understanding population dynamics in this region, evidence is presented herein on local population structure in the Arabian Peninsula, based on Y-STR characterisation in four Arabian samples and its comparison in a broad geographical scale. Our results demonstrate that geography played an important role in shaping the genetic structure of the region around the Near-East. Populations are grouped regionally but none of these groups is significantly differentiated from others and all groups merge in the Near-East, in keeping with this important migration corridor for the human species. Focusing on the Arabian Peninsula, we show that Dubai and Oman share genetic affinities with other Near-Eastern populations, while Saudi Arabia and Yemen show a relative distinctive isolated background. Those two populations may have been kept relatively separated from migration routes, maybe due to their location in a desert area.

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  • Néolithisation et chromosome Y en Afrique du Nord In: Serageldin I, Crubézy E, eds. Le peuplement de la Méditerranée : synthèse et questions d'avenir. Bibliotheca Alexandrina (Alexandria, Egypt) and Archéologie nouvelle (Paris, France), p. 115-125.

    abstract

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  • Worldwide distribution of NAT2 diversity: implications for NAT2 evolutionary history. BMC Genet. 2008 ;9():21. 1471-2156-9-21. 10.1186/1471-2156-9-21. PMC2292740.

    abstract

    The N-acetyltransferase 2 (NAT2) gene plays a crucial role in the metabolism of many drugs and xenobiotics. As it represents a likely target of population-specific selection pressures, we fully sequenced the NAT2 coding region in 97 Mandenka individuals from Senegal, and compared these sequences to extant data on other African populations. The Mandenka data were further included in a worldwide dataset composed of 41 published population samples (6,727 individuals) from four continental regions that were adequately genotyped for all common NAT2 variants so as to provide further insights into the worldwide haplotype diversity and population structure at NAT2.

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  • Genetic Diversity in Africa In: Encyclopedia of Life Sciences eLS(Chichester: John Wiley & Sons), 2008

    abstract

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  • The GM genetic polymorphism in Taiwan aborigines: New data revealing remarkable differentiation patterns In: Sanchez-Mazas A, Blench R, Ross M, Peiros I, Lin M, eds. Past human migrations in East Asia: matching archaeology, linguistics and genetics. Routledge, London and New York, p. 313-333 (2008)

    abstract

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  • The peopling of Europe In: Crawford MH, ed. Anthropological Genetics: Theory, Methods and Applications. Cambridge: Cambridge University Press, p. 380-408 (2007)

    abstract

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  • Haplotype tagging efficiency and tagSNP sets portability in worldwide populations in NAT2 gene (Marquage d'haplotypes du gène NAT2 : efficacité dans différentes régions du monde) Bull. et Mém. Soc. d'Anthropologie de Paris 19(3-4):233-241 (2007)

    abstract

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  • Comparing linguistic and genetic relationships among East Asian populations: a study of the RH and GM polymorphisms In: Sagart L, Blench R and Sanchez-Mazas A, eds. The peopling of East Asia : Putting together Archaeology, Linguistics and Genetics. London: RoutledgeCurzon, p. 250-272 (2005)

    abstract

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  • HLA genetic structure of East Asian populations: geography versus linguistics In: Sagart L, Blench R, Sanchez-Mazas A, eds. The peopling of East Asia : Putting together Archaeology, Linguistics and Genetics. London: RoutledgeCurzon, p. 273-296 (2005)

    abstract

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  • A predominantly neolithic origin for Y-chromosomal DNA variation in North Africa. Am. J. Hum. Genet. 2004 Aug;75(2):338-45. 10.1086/423147. S0002-9297(07)62417-3. PMC1216069.

    abstract

    We have typed 275 men from five populations in Algeria, Tunisia, and Egypt with a set of 119 binary markers and 15 microsatellites from the Y chromosome, and we have analyzed the results together with published data from Moroccan populations. North African Y-chromosomal diversity is geographically structured and fits the pattern expected under an isolation-by-distance model. Autocorrelation analyses reveal an east-west cline of genetic variation that extends into the Middle East and is compatible with a hypothesis of demic expansion. This expansion must have involved relatively small numbers of Y chromosomes to account for the reduction in gene diversity towards the West that accompanied the frequency increase of Y haplogroup E3b2, but gene flow must have been maintained to explain the observed pattern of isolation-by-distance. Since the estimates of the times to the most recent common ancestor (TMRCAs) of the most common haplogroups are quite recent, we suggest that the North African pattern of Y-chromosomal variation is largely of Neolithic origin. Thus, we propose that the Neolithic transition in this part of the world was accompanied by demic diffusion of Afro-Asiatic-speaking pastoralists from the Middle East.

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  • Genetic structure of Mediterranean populations revealed by Y-chromosome haplotype analysis. Am. J. Phys. Anthropol. 2003 Jun;121(2):157-71. 10.1002/ajpa.10187.

    abstract

    The allelic variability at six Y-chromosome-specific polymorphisms (YAP, DYS19, DYS389-I, DYS390, DYS391, and DYS392) was used to generate male-specific haplotypes in 333 males representing 12 population samples from the region around the Mediterranean sea. Extreme interindividual variation was observed, as more than 160 distinct Y-chromosome variants could be defined as six-locus haplotypes. Concomitant with this high variability, low levels of population genetic structure were observed. In particular, a "core" of populations directly facing the north and the east of the Mediterranean basin, from the Middle East to the Italian Peninsula, was found to be genetically undifferentiated. This observation, supported by a reanalysis of Y-specific binary polymorphisms in the same populations, suggests that at least part of the male-specific gene pools of these populations has either a very recent common origin (that could be related with the Neolithic demic diffusion hypothesis), and/or that gene flow has played a significant role in shaping the patterns of genetic variability in this region. In agreement with both hypotheses, we found that the spatial distribution of DYS392 alleles revealed a marked differentiation between the East and the West of the Mediterranean area. Through the analysis of microsatellite variation, the time to the most recent common ancestor (TMRCA) of the YAP(+) sublineage 4 has been estimated. The estimations, based on two different data sets, turn out to be quite recent (7,000-11,000 YBP), suggesting that this lineage may have been first introduced into Southern Europe through Neolithic migrations from the Middle East.

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  • Génétique, linguistique et histoire des peuplements humains Langages 146:80-90 (2002)

    abstract

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  • La langue paternelle Sciences et Avenir, Hors-série (Quelle langue parlait-on il y a 100 000 ans?: la langue d'Homo erectus) 125:42-49 (2000-2001)

    abstract

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  • The molecular diversity of the Niokholo Mandenkalu from Eastern Senegal: An insight into West Africa genetic history In: Boyce AJ and Mascie-Taylor CGN, eds. Molecular Biology and Human Diversity. Cambridge: Cambridge University Press, p.141-155 (1996)

    abstract

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  • Les différenciations génétiques des populations humaines révélées par le chromosome Y correspondent étroitement à leurs apparentements linguistiques Bulletin du Centre genevois d'anthropologie 5:82-85 (1995)

    abstract

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  • L'Homme descend du sexe La Recherche 20:994-1007 (1989)

    abstract

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