vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJGB-23-08vavilov-3632Research ArticleПОПУЛЯЦИОННАЯ ГЕНЕТИКА ЧЕЛОВЕКАHUMAN POPULATION GENETICSИдентичные по происхождению блоки в геномах коренного населения Сибири демонстрируют генетические связи между популяциямиBlocks identical by descent in the genomes of the indigenous population of Siberia demonstrate genetic links between populationshttps://orcid.org/0000-0001-8855-577XКолесниковН. А.KolesnikovN. A.

Томск,

Tomsk

nikita.kolesnikov@medgenetics.ruhttps://orcid.org/0000-0002-1679-2212ХарьковВ. Н.KharkovV. N.

Томск

Tomsk

https://orcid.org/0000-0003-4877-9749ВагайцеваК. В.VagaitsevaK. V.

Томск

Tomsk

https://orcid.org/0000-0001-6568-6339ЗарубинА. А.ZarubinA. A.

Томск

Tomsk

https://orcid.org/0000-0002-5166-331XСтепановВ. А.StepanovV. A.

Томск

Tomsk

Научно-исследовательский институт медицинской генетики, Томский национальный исследовательский медицинский центр Российской академии наукРоссияResearch Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesRussian Federation2023070320232715562Copyright © Колесников Н.А., Харьков В.Н., Вагайцева К.В., Зарубин А.А., Степанов В.А., 20232023Колесников Н.А., Харьков В.Н., Вагайцева К.В., Зарубин А.А., Степанов В.А.Kolesnikov N.A., Kharkov V.N., Vagaitseva K.V., Zarubin A.A., Stepanov V.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3632

Генофонд коренного населения Сибири представляет собой уникальную систему с точки зрения исследования популяционно- и эволюционно-генетических процессов, анализа генетического разнообразия и реконструкции генетической истории популяций. Высокое этническое разнообразие является особенностью Сибири как одного из регионов периферийного расселения современного человека. Огромные пространства этого региона и малочисленность аборигенного населения способствовали формированию значительной территориальной и генетической подразделенности. На территории сибирской историко-этнографической провинции расселены около 40 коренных народностей. Проведено масштабное популяционное исследование генофонда коренных народов Сибири на уровне высокоплотного ДНК-микрочипа Infinium Multi-Ethnic Global-8, позволяющее заполнить существенный пробел в геногеографической картине населения Евразии. Для этого были отобраны и проанализированы фрагменты ДНК, унаследованные без рекомбинации каждой парой индивидов от их недавнего общего предка, т. е. сегменты (блоки), идентичные по происхождению (IBD). Распределение блоков IBD в популяциях Сибири хорошо согласуется с географической близостью популяций и их языковой принадлежностью. Чукчи, коряки и нивхи среди сибирских популяций формируют отдельный от основной группы Сибири кластер, причем чукчи и коряки являются более близкородственными. Образуются отдельные субкластеры эвенков и якутов, кетов и чулымцев, тувинцев и алтайцев внутри сибирского кластера. Анализ SNP, которые попадали в большее количество IBD-сегментов анализируемых популяций, позволил составить список из 5358 генов. По результатам расчета, обогащенные этими генами биологические процессы связаны с обнаружением химического раздражителя, участвующего в сенсорном восприятии запаха. Обогащенные найденными генами молекулярные пути связаны с метаболизмом линолевой, арахидоновой, тирозиновой кислот и путем обонятельной трансдукции. При этом анализ литературных данных показал, что некоторые из отобранных генов, которые встречались в большем количестве блоков IBD сразу в нескольких популяциях, могут играть роль в адаптации человека к факторам окружающей среды.

The gene pool of the indigenous population of Siberia is a unique system for studying population and evolutionary genetic processes, analyzing genetic diversity, and reconstructing the genetic history of populations. High ethnic diversity is a feature of Siberia, as one of the regions of the peripheral settlement of modern human. The vast expanses of this region and the small number of aboriginal populations contributed to the formation of significant territorial and genetic subdivision. About 40 indigenous peoples are settled on the territory of the Siberian historical and ethnographic province. Within the framework of this work, a large-scale population study of the gene pool of the indigenous peoples of Siberia was carried out for the first time at the level of high-density biochips. This makes it possible to fill in a significant gap in the genogeographic picture of the Eurasian population. For this, DNA fragments were analyzed, which had been inherited without recombination by each pair of individuals from their recent common ancestor, that is, segments (blocks) identical by descent (IBD). The distribution of IBD blocks in the populations of Siberia is in good agreement with the geographical proximity of the populations and their linguistic affiliation. Among the Siberian populations, the Chukchi, Koryaks, and Nivkhs form a separate cluster from the main Siberian group, with the Chukchi and Koryaks being more closely related. Separate subclusters of Evenks and Yakuts, Kets and Chulyms are formed within the Siberian cluster. Analysis of SNPs that fell into more IBD segments of the analyzed populations made it possible to compile a list of 5358 genes. According to the calculation results, biological processes enriched with these genes are associated with the detection of a chemical stimulus involved in the sensory perception of smell. Enriched for the genes found, molecular pathways are associated with the metabolism of linoleic, arachidonic, tyrosic acids and by olfactory transduction. At the same time, an analysis of the literature data showed that some of the selected genes, which were found in a larger number of IBD blocks in several populations at once, can play a role in genetic adaptation to environmental factors.

IBDпопуляции человекасибирские популяцииIBDhuman populationsSiberian populationsThe study was supported by the Russian Science Foundation, grant No. 22-64-00060, (https://rscf.ru/project/22-64-00060/).ReferencesAlbrechtsen A., Moltke I., Nielsen R. Natural selection and the distribution of identity-by-descent in the human genome. Genetics. 2010; 186(1):295-308. DOI 10.1534/genetics.110.113977.Albrechtsen A., Moltke I., Nielsen R. Natural selection and the distribution of identity-by-descent in the human genome. Genetics. 2010; 186(1):295-308. DOI 10.1534/genetics.110.113977.Amorim C.E.G., Nunes K., Meyer D., Comas D., Bortolini M.C., Salzano F.M., Hünemeier T. Genetic signature of natural selection in first Americans. Proc. Natl. Acad. Sci. USA. 2017;114(9):2195-2199. DOI 10.1073/pnas.1620541114.Amorim C.E.G., Nunes K., Meyer D., Comas D., Bortolini M.C., Salzano F.M., Hünemeier T. Genetic signature of natural selection in first Americans. Proc. Natl. Acad. Sci. USA. 2017;114(9):2195-2199. DOI 10.1073/pnas.1620541114.Bamodu O.A., Wang Y.H., Ho C.H., Hu S.W., Lin C.D., Tzou K.Y., Wu W.L., Chen K.C., Wu C.C. Genetic suppressor element 1 (GSE1) promotes the oncogenic and recurrent phenotypes of castration-resistant prostate cancer by targeting tumor-associated calcium signal transducer 2 (TACSTD2). Cancers (Basel). 2021;13(16):3959. DOI 10.3390/cancers13163959.Bamodu O.A., Wang Y.H., Ho C.H., Hu S.W., Lin C.D., Tzou K.Y., Wu W.L., Chen K.C., Wu C.C. Genetic suppressor element 1 (GSE1) promotes the oncogenic and recurrent phenotypes of castration-resistant prostate cancer by targeting tumor-associated calcium signal transducer 2 (TACSTD2). Cancers (Basel). 2021;13(16):3959. DOI 10.3390/cancers13163959.Bownes R.J., Turnbull A.K., Martinez-Perez C., Cameron D.A., Sims A.H., Oikonomidou O. On-treatment biomarkers can improve prediction of response to neoadjuvant chemotherapy in breast cancer. Breast Cancer Res. 2019;21(1):73. DOI 10.1186/s13058-019-1159-3.Bownes R.J., Turnbull A.K., Martinez-Perez C., Cameron D.A., Sims A.H., Oikonomidou O. On-treatment biomarkers can improve prediction of response to neoadjuvant chemotherapy in breast cancer. Breast Cancer Res. 2019;21(1):73. DOI 10.1186/s13058-019-1159-3.Browning B.L., Browning S.R. Improving the accuracy and efficiency of identity-by-descent detection in population data. Genetics. 2013; 194(2):459-471. DOI 10.1534/genetics.113.150029.Browning B.L., Browning S.R. Improving the accuracy and efficiency of identity-by-descent detection in population data. Genetics. 2013; 194(2):459-471. DOI 10.1534/genetics.113.150029.Browning S.R., Browning B.L. Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. Am. J. Hum. Genet. 2007; 81(5):1084-1097. DOI 10.1086/521987.Browning S.R., Browning B.L. Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. Am. J. Hum. Genet. 2007; 81(5):1084-1097. DOI 10.1086/521987.Browning S.R., Browning B.L. High-resolution detection of identity by descent in unrelated individuals. Am. J. Hum. Genet. 2010;86(4): 526-539. DOI 10.1016/j.ajhg.2010.02.021.Browning S.R., Browning B.L. High-resolution detection of identity by descent in unrelated individuals. Am. J. Hum. Genet. 2010;86(4): 526-539. DOI 10.1016/j.ajhg.2010.02.021.Calder P.C. Long chain fatty acids and gene expression in inflammation and immunity. Curr. Opin. Clin. Nutr. Metab. Care. 2013;16(4): 425-433. DOI 10.1097/MCO.0b013e3283620616.Calder P.C. Long chain fatty acids and gene expression in inflammation and immunity. Curr. Opin. Clin. Nutr. Metab. Care. 2013;16(4): 425-433. DOI 10.1097/MCO.0b013e3283620616.Chilton F.H., Murphy R.C., Wilson B.A., Sergeant S., Ainsworth H., Seeds M.C., Mathias R.A. Diet-gene interactions and PUFA metabolism: A potential contributor to health disparities and human diseases. Nutrients. 2014;6(5):1993-2022. DOI 10.3390/nu6051993.Chilton F.H., Murphy R.C., Wilson B.A., Sergeant S., Ainsworth H., Seeds M.C., Mathias R.A. Diet-gene interactions and PUFA metabolism: A potential contributor to health disparities and human diseases. Nutrients. 2014;6(5):1993-2022. DOI 10.3390/nu6051993.Christakis N.A., Fowler J.H. Friendship and natural selection. Proc. Natl. Acad. Sci. USA. 2014;111(Suppl. 3):10796-10801. DOI 10.1073/pnas.1400825111.Christakis N.A., Fowler J.H. Friendship and natural selection. Proc. Natl. Acad. Sci. USA. 2014;111(Suppl. 3):10796-10801. DOI 10.1073/pnas.1400825111.Espeseth T., Sneve M.H., Rootwelt H., Laeng B. Nicotinic receptor gene CHRNA4 interacts with processing load in attention. PLoS One. 2010;5(12):e14407. DOI 10.1371/journal.pone.0014407.Espeseth T., Sneve M.H., Rootwelt H., Laeng B. Nicotinic receptor gene CHRNA4 interacts with processing load in attention. PLoS One. 2010;5(12):e14407. DOI 10.1371/journal.pone.0014407.Fei Y., Li Y., Chen F. LncRNA-IQCH-AS1 sensitizes thyroid cancer cells to doxorubicin via modulating the miR-196a-5p/PPP2R1B signalling pathway. J. Chemother. 2022;1-9. DOI 10.1080/1120009X.2022.2082348.Fei Y., Li Y., Chen F. LncRNA-IQCH-AS1 sensitizes thyroid cancer cells to doxorubicin via modulating the miR-196a-5p/PPP2R1B signalling pathway. J. Chemother. 2022;1-9. DOI 10.1080/1120009X.2022.2082348.Fu F., Nowak M.A., Christakis N.A., Fowler J.H. The evolution of homophily. Sci. Rep. 2012;2:845. DOI 10.1038/srep00845.Fu F., Nowak M.A., Christakis N.A., Fowler J.H. The evolution of homophily. Sci. Rep. 2012;2:845. DOI 10.1038/srep00845.Fumagalli M., Moltke I., Grarup N., Racimo F., Bjerregaard P., Jørgensen M.E., Korneliussen T.S., Gerbault P., Skotte L., Linneberg A., Christensen C., Brandslund I., Jørgensen T., Huerta-Sánchez E., Schmidt E.B., Pedersen O., Hansen T., Albrechtsen A., Nielsen R. Greenlandic Inuit show genetic signatures of diet and climate adaptation. Science. 2015;349(6254):1343-1347. DOI 10.1126/science.aab2319.Fumagalli M., Moltke I., Grarup N., Racimo F., Bjerregaard P., Jørgensen M.E., Korneliussen T.S., Gerbault P., Skotte L., Linneberg A., Christensen C., Brandslund I., Jørgensen T., Huerta-Sánchez E., Schmidt E.B., Pedersen O., Hansen T., Albrechtsen A., Nielsen R. Greenlandic Inuit show genetic signatures of diet and climate adaptation. Science. 2015;349(6254):1343-1347. DOI 10.1126/science.aab2319.Grazioplene R.G., Deyoung C.G., Rogosch F.A., Cicchetti D. A novel differential susceptibility gene: CHRNA4 and moderation of the effect of maltreatment on child personality. J. Child Psychol. Psychiatry. 2013;54(8):872-880. DOI 10.1111/jcpp.12031.Grazioplene R.G., Deyoung C.G., Rogosch F.A., Cicchetti D. A novel differential susceptibility gene: CHRNA4 and moderation of the effect of maltreatment on child personality. J. Child Psychol. Psychiatry. 2013;54(8):872-880. DOI 10.1111/jcpp.12031.Gusev A., Palamara P.F., Aponte G., Zhuang Z., Darvasi A., Gregersen P., Pe’er I. The architecture of long-range haplotypes shared within and across populations. Mol. Biol. Evol. 2012;29(2):473-486. DOI 10.1093/molbev/msr133.Gusev A., Palamara P.F., Aponte G., Zhuang Z., Darvasi A., Gregersen P., Pe’er I. The architecture of long-range haplotypes shared within and across populations. Mol. Biol. Evol. 2012;29(2):473-486. DOI 10.1093/molbev/msr133.Han L., Abney M. Identity by descent estimation with dense genomewide genotype data. Genet. Epidemiol. 2011;35(6):557-567. DOI 10.1002/gepi.20606.Han L., Abney M. Identity by descent estimation with dense genomewide genotype data. Genet. Epidemiol. 2011;35(6):557-567. DOI 10.1002/gepi.20606.Harris D.N., Ruczinski I., Yanek L.R., Becker L.C., Becker D.M., Guio H., Cui T., Chilton F.H., Mathias R.A., O’Connor T.D. Evolution of hominin polyunsaturated fatty acid metabolism: from Africa to the New World. Genome Biol. Evol. 2019;11(5):1417-1430. DOI 10.1093/gbe/evz071.Harris D.N., Ruczinski I., Yanek L.R., Becker L.C., Becker D.M., Guio H., Cui T., Chilton F.H., Mathias R.A., O’Connor T.D. Evolution of hominin polyunsaturated fatty acid metabolism: from Africa to the New World. Genome Biol. Evol. 2019;11(5):1417-1430. DOI 10.1093/gbe/evz071.Hochreiter S. HapFABIA: Identification of very short segments of identity by descent characterized by rare variants in large sequencing data. Nucleic Acids Res. 2013;41(22):e202. DOI 10.1093/nar/gkt1013.Hochreiter S. HapFABIA: Identification of very short segments of identity by descent characterized by rare variants in large sequencing data. Nucleic Acids Res. 2013;41(22):e202. DOI 10.1093/nar/gkt1013.Horrocks L.A., Yeo Y.K. Health benefits of docosahexaenoic acid (DHA). Pharmacol. Res. 1999;40(3):211-225. DOI 10.1006/phrs.1999.0495.Horrocks L.A., Yeo Y.K. Health benefits of docosahexaenoic acid (DHA). Pharmacol. Res. 1999;40(3):211-225. DOI 10.1006/phrs.1999.0495.Howe P., Meyer B., Record S., Baghurst K. Dietary intake of longchain ω-3 polyunsaturated fatty acids: contribution of meat sources. Nutrition. 2006;22(1):47-53. DOI 10.1016/j.nut.2005.05.009.Howe P., Meyer B., Record S., Baghurst K. Dietary intake of longchain ω-3 polyunsaturated fatty acids: contribution of meat sources. Nutrition. 2006;22(1):47-53. DOI 10.1016/j.nut.2005.05.009.Kimura T., Kobayashi T., Munkhbat B., Oyungerel G., Bilegtsaikhan T., Anar D., Jambaldorj J., Munkhsaikhan S., Munkhtuvshin N., Hayashi H., Oka A., Inoue I., Inoko H. Genome-wide association analysis with selective genotyping identifies candidate loci for adult height at 8q21.13 and 15q22.33-q23 in Mongolians. Hum. Genet. 2008; 123(6):655-660. DOI 10.1007/s00439-008-0512-x.Kimura T., Kobayashi T., Munkhbat B., Oyungerel G., Bilegtsaikhan T., Anar D., Jambaldorj J., Munkhsaikhan S., Munkhtuvshin N., Hayashi H., Oka A., Inoue I., Inoko H. Genome-wide association analysis with selective genotyping identifies candidate loci for adult height at 8q21.13 and 15q22.33-q23 in Mongolians. Hum. Genet. 2008; 123(6):655-660. DOI 10.1007/s00439-008-0512-x.Kiritsi D., Chmel N., Arnold A.W., Jakob T., Bruckner-Tuderman L., Has C. Novel and recurrent AAGAB mutations: clinical variability and molecular consequences. J. Invest. Dermatol. 2013;133(10): 2483-2486. DOI 10.1038/jid.2013.171.Kiritsi D., Chmel N., Arnold A.W., Jakob T., Bruckner-Tuderman L., Has C. Novel and recurrent AAGAB mutations: clinical variability and molecular consequences. J. Invest. Dermatol. 2013;133(10): 2483-2486. DOI 10.1038/jid.2013.171.Kolesnikov N.A., Kharkov V.N., Zarubin A.A., Radzhabov M.O., Voevoda M.I., Gubina M.A., Khusnutdinova E.K., Litvinov S.S., Ekomasova N.V., Shtygasheva O.V., Maksimova N.R., Sukhomyasova A.L., Stepanov V.A. Features of the genomic distribution of runs of homozygosity in the indigenous population of Northern Eurasia at the individual and population levels based on high density SNP analysis. Russ. J. Genet. 2021;57(11):1271-1284. DOI 10.1134/S1022795421110053.Kolesnikov N.A., Kharkov V.N., Zarubin A.A., Radzhabov M.O., Voevoda M.I., Gubina M.A., Khusnutdinova E.K., Litvinov S.S., Ekomasova N.V., Shtygasheva O.V., Maksimova N.R., Sukhomyasova A.L., Stepanov V.A. Features of the genomic distribution of runs of homozygosity in the indigenous population of Northern Eurasia at the individual and population levels based on high density SNP analysis. Russ. J. Genet. 2021;57(11):1271-1284. DOI 10.1134/S1022795421110053.Kuhlwilm M., Boeckx C. A catalog of single nucleotide changes distinguishing modern humans from archaic hominins. Sci. Rep. 2019; 9(1):8463. DOI 10.1038/s41598-019-44877-x.Kuhlwilm M., Boeckx C. A catalog of single nucleotide changes distinguishing modern humans from archaic hominins. Sci. Rep. 2019; 9(1):8463. DOI 10.1038/s41598-019-44877-x.Marszalek J.R., Lodish H.F. Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. Annu. Rev. Cell Dev. Biol. 2005;21:633-657. DOI 10.1146/annurev.cellbio.21.122303.120624.Marszalek J.R., Lodish H.F. Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. Annu. Rev. Cell Dev. Biol. 2005;21:633-657. DOI 10.1146/annurev.cellbio.21.122303.120624.Palamara P.F., Lencz T., Darvasi A., Pe’er I. Length distributions of identity by descent reveal fine-scale demographic history. Am. J. Hum. Genet. 2012;91(5):809-822. DOI 10.1016/j.ajhg.2012.08.030.Palamara P.F., Lencz T., Darvasi A., Pe’er I. Length distributions of identity by descent reveal fine-scale demographic history. Am. J. Hum. Genet. 2012;91(5):809-822. DOI 10.1016/j.ajhg.2012.08.030.Pugach I., Matveev R., Spitsyn V., Makarov S., Novgorodov I., Osakovsky V., Stoneking M., Pakendorf B. The complex admixture history and recent southern origins of Siberian populations. Mol. Biol. Evol. 2016;33(7):1777-1795. DOI 10.1093/molbev/msw055.Pugach I., Matveev R., Spitsyn V., Makarov S., Novgorodov I., Osakovsky V., Stoneking M., Pakendorf B. The complex admixture history and recent southern origins of Siberian populations. Mol. Biol. Evol. 2016;33(7):1777-1795. DOI 10.1093/molbev/msw055.Tucci S., Vohr S.H., McCoy R.C., Vernot B., Robinson M.R., Barbieri C., Nelson B.J., Fu W., Purnomo G.A., Sudoyo H., Eichler E.E., Barbujani G., Visscher P.M., Akey J.M., Green R.E. Evolutionary history and adaptation of a human pygmy population of Flores Island, Indonesia. Science. 2018;361(6401):511-516. DOI 10.1126/science.aar8486.Tucci S., Vohr S.H., McCoy R.C., Vernot B., Robinson M.R., Barbieri C., Nelson B.J., Fu W., Purnomo G.A., Sudoyo H., Eichler E.E., Barbujani G., Visscher P.M., Akey J.M., Green R.E. Evolutionary history and adaptation of a human pygmy population of Flores Island, Indonesia. Science. 2018;361(6401):511-516. DOI 10.1126/science.aar8486.Yin L.L., Li J.M., Zhou Z.M., Sha J.H. Identification of a novel testisspecific gene and its potential roles in testis development/spermatogenesis. Asian J. Androl. 2005;7(2):127-137. DOI 10.1111/j.1745-7262.2005.00041.x.Yin L.L., Li J.M., Zhou Z.M., Sha J.H. Identification of a novel testisspecific gene and its potential roles in testis development/spermatogenesis. Asian J. Androl. 2005;7(2):127-137. DOI 10.1111/j.1745-7262.2005.00041.x.

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