2658-6533Научные результаты биомедицинских исследований2658-653310.18413/2658-6533-2020- 6-3-0-42106Генетика<strong>Современная геномика в изучении проблем адаптации человека к климату в высоких широтах Сибири</strong><strong>Modern genomics in studying the problems of human adaptation to climate in north Siberia</strong>ОсиповаЛюдмила ПавловнаOsipovaLudmila P.ludos77@yandex.ruЛичманДарья ВениаминовнаLichmanDaria V.daria.lichman@gmail.comХоллмаркБрайанHallmarkBrianbhallmark@statlab.bio5.orgКарафетТатьяна МихайловнаKarafetTatiana M.tkarafet@email.arizona.eduСиэПэн СанHsiehPing Hsunhsiehph@u.washington.eduУоткинсДжозеф С.WatkinsJoseph C.jwatkins@math.arizona.eduХаммерМайкл Ф.HammerMichael F.mfh@email.arizona.edu20206300

Актуальность: Коренные жители Сибири живут в экстремально суровых природных условиях на Земле, испытывая на себе длительное воздействие холода, сильных колебаний продолжительности светового дня и довольно ограниченного рациона питания. Очевидно, что успешное освоение человеком столь сложных для проживания территорий связано не только с культурной, но и с генетической адаптацией. Однако конкретные механизмы генетического приспособления к холодному климату, а также к диете с высоким содержанием животных жиров до сих пор остаются мало изученными. Цель исследования: Поиск маркеров полигенного отбора к климатическому стрессу в высоких северных широтах и пищевому рациону, основанному на богатой животными жирами пище. Материалы и методы: Исследование состояло из трёх этапов. На первом этапе в популяциях нганасан Таймыра (N=21) и якутов Республики Саха (N=21) выполнены отборочное полноэкзомное сканирование и полногеномный анализ однонуклеотидных замен (SNP). На втором этапе в &laquo;хвостах&raquo; эмпирических распределений выявлены гены-кандидаты, связанные с биологическими процессами и фенотипами, имеющими отношение к адаптации в циркумполярных группах. На третьем этапе лучшие кандидаты генотипированы в дополнительных популяциях Сибири, чтобы определить пространственное распределение частот аллелей и их ассоциации с климатическими переменными. Результаты: Были выявлены гены-кандидаты, из которых наибольший интерес представили гены PLA2G2A, PLIN1, ANGPTL8, вовлечённые в липидный метаболизм и связанные с бурой жировой тканью. В этих генах обнаружены несинонимичные замены, распространённость которых в северных популяциях указывает на вероятное воздействие естественного отбора. Заключение: Полученные результаты подтверждают гипотезу о том, что коренные популяции Сибири генетически адаптировались к жёсткой среде обитания путем отбора по нескольким генам, имеющим отношение к метаболизму жиров.

Background: Indigenous people of north Siberia live in some of the harshest natural conditions on Earth, experiencing prolonged exposure to cold, large fluctuations in the length of daylight, and a limited diet. It is obvious that the successful occupation of such extremely difficult territories is connected not only with cultural but also with genetic adaptation. However, specific mechanisms of genetic adaptation to the cold climate and animal fat-rich diet still remain poorly understood. The aim of the study: To explore markers of polygenic selection for fat-rich diet and climate stress in the high northern latitudes. Materials and methods: The study consisted of three stages. At the first stage, we performed selection scans on whole exome and genome-wide single nucleotide polymorphism array data from the populations of Nganasans (N=21) and Yakuts (N=21). At the second stage, in the tails of empirical distributions, candidate genes associated with biological processes and phenotypes related to adaptation in circumpolar groups were revealed. At the third stage, the best candidates were genotyped in additional Siberian populations to determine the spatial distribution of allele frequencies and their associations with climatic variables. Results: We have identified several candidate genes, the most relevant being PLA2G2A, PLIN1, and ANGPTL8 genes involved in lipid metabolism and related to brown adipose tissue. Missense mutations in these genes exhibit spatial patterns consistent with selection for cold climate and/or diet. Conclusion: The results support the hypothesis that indigenous populations in Siberia have genetically adapted to harsh environments by selection on multiple genes related mostly to fat metabolism.

генетика популяцийестественный отборхолодный климатлипидный обменгены PLA2G2APLIN1ANGPTL8однонуклеотидный полиморфизмpopulation geneticsnatural selectioncold climatelipid metabolismsingle nucleotide polymorphismPLA2G2APLIN1and ANGPTL8 genes

Работа была поддержана грантом РНФ № 19-15-00219.

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