Genetics of adaptive traits and gender-specific demographic processes in South Asian populations
Date
2014-12-10
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Abstract
Oma kuulsas, enam kui 140 aasta eest avaldatud raamatus “Inimese põlvnemine”, pööras suur Briti loodusteadlane Charles Darwin olulist tähelepanu inimpopulatsioonide varieerumisele. Ta põhjendas veenvalt, et vaatamata märkimisväärsele fenotüüpsele ja kultuurilisele mitmekesisusele on inimkonda õige ette kujutada ühtse rassina, kes jagab kusagil sügavas minevikus ühist päritolu suurte inimahvidega. Lisaks juhtis ta tähelepanu asjaolule, et oluline osa sellest mitmekesisusest on seletatav loodusliku valikuga ning rõhutas populatsioonide segunemise võimalikku tähtsust. Darwini mõtted omasid ulatuslikku mõju nii teaduses kui laiemalt, kuid alles viimase paarikümne aasta jooksul, seoses uute uurimismeetodite kasutuselevõtmisega, oleme me hakanud mõistma fenotüüpse varieeruvuse geneetilist tausta. Populatsioonigeneetika on tänu andmekogumise ja analüüsi meetodite täiustumisele muutunud kiiresti arenevaks uurimissuunaks. Samas on see alles arengu algfaasis, sest põhjuslikud seletused nõuavad geneetika ja genoomika sünteesi ja evolutsioonilist argumentatsiooni koos süvateadmistega inimese füsioloogiast, biokeemiast ja arengubioloogiast, mis on sageli põimunud meie kui liigi sotsiaalse ja kultuurilise arenguga laiemas tähenduses.
Lõuna-Aasia keeleline, sotsiaalne ja fenotüübiline vahelduvus pakub võimaluse uurida erinevaid evolutsioonilisi hüpoteese detailiderikkas mudelsüsteemis eesmärgiga rekonstrueerida sündmusi, mis on kujundanud meid selliseks, nagu me oleme tänapäeval. Käesolevas doktoritöös on Lõuna-Aasia populatsioonid mudeliks kahe laiema eesmärgi täitmisel. Esmalt, leida geneetilised tegurid kahele inimesele kui liigile olulisele kohastumusele - nahavärvile ja laktaasi aktiivsuse elukestvale püsimisele (LAEP), võimele seedida piimasuhkrut ka täiskasvanuna. Teiseks, rekonstrueerida Lõuna- ja Kagu-Aasias elavate austroaasia keeli rääkivate rahvaste demograafiline ajalugu.
Ekspeditsioonil Indiasse mõõtsime kohalike elanike nahapigmentatsiooni. Leidsime, et India elanike nahavärv varieerub suures ulatuses ning selle eest vastutab olulisel määral SLC24A5 geen. Uurisime selle lookuse erinevate alleelide tänast esinemissagedust mõjutanud loodusliku valiku mustreid, fülogeneetilisi suhted ja varieeruvust inimpopulatsioonides üle maailma. Leidsime, et Lääne-Euraasia ja Lõuna-Aasia elanikel on ühine heleda nahavärviga seotud SLC24A5 geeni variant, mis on ühtlasi evolutsiooniliselt samatekkeline. Laktaasi geeni LCT võimendusjärjestuse piirkonna uuring andis põhjaliku ülevaate LAEP`i põhjustest Lõuna-Aasias. Naha värvi ja LAEP’i põhjustavate kandidaat-SNPde (rs1426654 ja -13910T) fülogeograafiline uuring näitas, et nende tunnuste evolutsioonis on olulised loodusliku valiku ja demograafia ühismõjud. Töö teise eesmärgi saavutamiseks kasutasime erinevaid andmestikke - üle kogu genoomi jaotunud autosoomseid SNPsid, ema- ja isaliine. Just autosoomsete SNPde analüüs tõi esmakordselt tõendeid kahesuunalisest geenivoolust Bengali lahe kallastel. Väidame, et tänapäeva India austroaasia keeli, vähemalt munda keeli, kõnelevad rahvad pärinevad Kagu-Aasia väljarännetest ja hilisemast segunemisest India elanikega. Töö tulemused toovad esile tänapäeva Lõuna-Aasia populatsioonide geneetilist struktuuri mõjutanud demograafilised protsessid ja on oluliselt parandanud uuritud kohastumuste üldist mõistmist.
In “The Descent of Man”, his famous book published more than 140 years ago, the great British naturalist Charles Darwin, devoted much attention to the variation within and across human populations. He convincingly argued that humanity, irrespective of considerable phenotypic and cultural differences, is a single race that shares a common root with greater apes in some distant past. Furthermore, he also pointed out that much of the observed variation can be explained by natural selection and stressed on the potential role of admixture between human communities. Darwin’s ideas had a considerable influence both for science and much wider. But only over the last decades, with better approaches available, we are beginning to understand the genetic basis of the phenotypic variation and various human adaptations. The field of population genetics, with its advancements in data acquisition and analysis, is by now a fast-growing active field of scientific enquiry, yet very much still in its initial stages, because causative explanations require synthesis of genetics and genomics, evolutionary reasoning, with in-depth knowledge of human physiology, biochemistry and developmental biology, often linked to social and cultural advancements of our species in a broader sense. South Asia, bearing in mind geographic, linguistic, socio-cultural and phenotypic diversity of the region, offers a rich in detailed model system to test various evolutionary hypotheses and to reconstruct the events that helped us to shape what we are today. Hence, in the current dissertation, we have broadly covered two general aims related to human diversity. Firstly, to decipher the genetic attributes of two important adaptive traits in humans - skin color and lactase persistence (the unique ability to digest lactose in adulthood) and secondly, to reconstruct the population history of Austroasiatic-speaking populations presently settled in South and Southeast Asia. Our expedition, involving skin color measurements, reflected high pigmentation diversity among local inhabitants. Our further analyses revealed SLC24A5 as one of the main determinants of skin pigmentation variation among South Asians. Additionally, an evolutionary approach was used to study the gene and important insights on the selection patterns, phylogenetic relationships and diversity patterns among global populations were obtained. We found that light skin associated variant of SLC24A5, shared by West Eurasians and South Asians, occur on the same haplotype background and we suggest its identity by descent. Our study of enhancer region of LCT among Indian populations provided a comprehensive view on the genetic basis of lactase persistence in the subcontinent. Phylogeography of the important candidate SNPs for the studied traits further revealed that combination of processes involving selection and demography have been crucial in the evolution of these traits. An integrated genetic approach of mitochondrial DNA, Y chromosome and autosomes to delineate the ancestry palette of Austroasiatic-speaking populations refined our understanding of their origin and dispersal routes. Autosomal analyses, in particular, provided the first evidence of bidirectional gene flow(s) alongside of the Bay-of-Bengal. We propose that the present-day Austroasiatics, at least in case of Munda, are derived from dispersal from Southeast Asia, followed by admixture with local Indian populations. The conclusions obtained in the dissertation thus bear significance in improving our general understanding of the evolutionary architecture of the studied adaptive traits and unique demographic processes that govern the genetic structuring of the present-day South Asians.
In “The Descent of Man”, his famous book published more than 140 years ago, the great British naturalist Charles Darwin, devoted much attention to the variation within and across human populations. He convincingly argued that humanity, irrespective of considerable phenotypic and cultural differences, is a single race that shares a common root with greater apes in some distant past. Furthermore, he also pointed out that much of the observed variation can be explained by natural selection and stressed on the potential role of admixture between human communities. Darwin’s ideas had a considerable influence both for science and much wider. But only over the last decades, with better approaches available, we are beginning to understand the genetic basis of the phenotypic variation and various human adaptations. The field of population genetics, with its advancements in data acquisition and analysis, is by now a fast-growing active field of scientific enquiry, yet very much still in its initial stages, because causative explanations require synthesis of genetics and genomics, evolutionary reasoning, with in-depth knowledge of human physiology, biochemistry and developmental biology, often linked to social and cultural advancements of our species in a broader sense. South Asia, bearing in mind geographic, linguistic, socio-cultural and phenotypic diversity of the region, offers a rich in detailed model system to test various evolutionary hypotheses and to reconstruct the events that helped us to shape what we are today. Hence, in the current dissertation, we have broadly covered two general aims related to human diversity. Firstly, to decipher the genetic attributes of two important adaptive traits in humans - skin color and lactase persistence (the unique ability to digest lactose in adulthood) and secondly, to reconstruct the population history of Austroasiatic-speaking populations presently settled in South and Southeast Asia. Our expedition, involving skin color measurements, reflected high pigmentation diversity among local inhabitants. Our further analyses revealed SLC24A5 as one of the main determinants of skin pigmentation variation among South Asians. Additionally, an evolutionary approach was used to study the gene and important insights on the selection patterns, phylogenetic relationships and diversity patterns among global populations were obtained. We found that light skin associated variant of SLC24A5, shared by West Eurasians and South Asians, occur on the same haplotype background and we suggest its identity by descent. Our study of enhancer region of LCT among Indian populations provided a comprehensive view on the genetic basis of lactase persistence in the subcontinent. Phylogeography of the important candidate SNPs for the studied traits further revealed that combination of processes involving selection and demography have been crucial in the evolution of these traits. An integrated genetic approach of mitochondrial DNA, Y chromosome and autosomes to delineate the ancestry palette of Austroasiatic-speaking populations refined our understanding of their origin and dispersal routes. Autosomal analyses, in particular, provided the first evidence of bidirectional gene flow(s) alongside of the Bay-of-Bengal. We propose that the present-day Austroasiatics, at least in case of Munda, are derived from dispersal from Southeast Asia, followed by admixture with local Indian populations. The conclusions obtained in the dissertation thus bear significance in improving our general understanding of the evolutionary architecture of the studied adaptive traits and unique demographic processes that govern the genetic structuring of the present-day South Asians.
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Keywords
rahvastikuprotsessid, populatsioonigeneetika, inimese evolutsioon, füsioloogiline kohanemine, laktoositalumatus, pigmentatsioon, geneetiline muutlikkus, fenotüübiline muutlikkus, Lõuna-Aasia, Euraasia, population processes, population genetics, anthropogenesis, physiological adaptation, lactose intolerance, pigmentation, geneetiline muutlikkus, phenotypic variation, South Asia, Eurasia