vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJGB-23-28vavilov-3733Research ArticleГЕНЕТИКА ЧЕЛОВЕКАHUMAN GENETICSОценка роли отбора в эволюции митохондриальных геномов коренного населения СибириEvaluating the role of selection in the evolution of mitochondrial genomes of aboriginal peoples of Siberiahttps://orcid.org/0000-0002-0304-0652МалярчукБ. А.MalyarchukB. A.

Магадан

Magadan

malyarchuk@ibpn.ruhttps://orcid.org/0000-0002-1849-784XДеренкоМ. В.DerenkoM. V.

Магадан

Magadan

Институт биологических проблем Севера Дальневосточного отделения Российской академии наукРоссияInstitute of Biological Problems of the North of the Far Eastern Branch of the Russian Academy of SciencesRussian Federation202302062023273218223Copyright © Малярчук Б.А., Деренко М.В., 20232023Малярчук Б.А., Деренко М.В.Malyarchuk B.A., Derenko M.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3733

Исследования характера изменчивости митохондриальной ДНК (мтДНК) в популяциях человека вы­явили, что белок­кодирующие гены находятся под действием отрицательного (очищающего) отбора, поскольку мутационные спектры генов мтДНК характеризуются выраженным преобладанием синонимичных замен над несинонимичными (величина параметра Ka/Ks < 1). Между тем в ряде исследований показано, что адаптация популяций к различным условиям природной среды может сопровождаться ослаблением отрицательного от­бора в некоторых генах мтДНК. Так, ранее было установлено, что в арктических популяциях отрицательный отбор ослаблен в митохондриальном гене ATP6, кодирующем одну из субъединиц АТФ­синтазы. В настоящей работе проведен Ka/Ks­анализ митохондриальных генов в больших выборках трех региональных групп населения Евразии: Сибири (N = 803), Западной Азии/Закавказья (N = 753) и Восточной Европы (N = 707). Основная цель работы – поиск следов адаптивной эволюции в генах мтДНК коренного населения Сибири, представлен­ного населением севера (коряки, эвены) и юга Сибири и прилегающей территории Северо­Восточного Китая (буряты, баргуты, хамнигане). С помощью стандартного Ka/Ks­анализа установлено, что все гены мтДНК во всех изученных региональных группах населения испытывают действие отрицательного отбора. Наиболее высокие значения Ka/Ks в различных региональных выборках обнаружены практически в одном и том же наборе генов, кодирующих субъединицы АТФ­синтазы (ATP6, ATP8), НАДН­дегидрогеназного комплекса (ND1, ND2, ND3) и ци­тохром bc1­комплекса (CYB). Самое высокое значение Ka/Ks, указывающее на ослабление отрицательного от­бора, выявлено в гене ATP6 в сибирской группе. Результаты анализа, выполненного с помощью метода FUBAR (пакет программ HyPhy) и направленного на поиск кодонов мтДНК, находящихся под действием отбора, также показали преобладание влияния отрицательного отбора над положительным отбором во всех группах населе­ния. В сибирских популяциях нуклеотидные позиции, находящиеcя под действием положительного отбора и ассоциированные с гаплогруппами мтДНК, зарегистрированы не на севере (что ожидается в предположении адаптивной эволюции мтДНК), а на юге Сибири.

Studies of the nature of mitochondrial DNA (mtDNA) variability in human populations have shown that protein­coding genes are under negative (purifying) selection, since their mutation spectra are characterized by a pro­ nounced predominance of synonymous substitutions over non­synonymous ones (Ka/Ks < 1). Meanwhile, a number of studies have shown that the adaptation of populations to various environmental conditions may be accompanied by a relaxation of negative selection in some mtDNA genes. For example, it was previously found that in Arctic populations, negative selection is relaxed in the mitochondrial ATP6 gene, which encodes one of the subunits of ATP synthase. In this work, we performed a Ka/Ks analysis of mitochondrial genes in large samples of three regional population groups in Eurasia: Siberia (N = 803), Western Asia/Transcaucasia (N = 753), and Eastern Europe (N = 707). The main goal of this work is to search for traces of adaptive evolution in the mtDNA genes of aboriginal peoples of Siberia represented by populations of the north (Koryaks, Evens) and the south of Siberia and the adjacent territory of Northeast China (Bu­ryats, Barghuts, Khamnigans). Using standard Ka/Ks analysis, it was found that all mtDNA genes in all studied regional population groups are subject to negative selection. The highest Ka/Ks values in different regional samples were found in almost the same set of genes encoding subunits of ATP synthase (ATP6, ATP8), NADH dehydrogenase complex (ND1, ND2, ND3), and cytochrome bc1 complex (CYB). The highest Ka/Ks value, indicating a relaxation of negative selection, was found in the ATP6 gene in the Siberian group. The results of the analysis performed using the FUBAR method (HyPhy software package) and aimed at searching for mtDNA codons under the influence of selection also showed the predominance of negative selection over positive selection in all population groups. In Siberian populations, nucleotide sites that are under positive selection and associated with mtDNA haplogroups were registered not in the north (which is expected under the assumption of adaptive evolution of mtDNA), but in the south of Siberia.

митохондриальная ДНКестественный отборKa/Ks­тестыпопуляции человекаСибирьmitochondrial DNAnatural selectionKa/Ks­testinghuman populationsSiberiaReferencesBrown W.M., George M.Jr., Wilson A.C. Rapid evolution of animal mitochondrial DNA. Proc. Natl. Acad. Sci. USA. 1979;76(4):19671971. DOI 10.1073/pnas.76.4.1967.Brown W.M., George M.Jr., Wilson A.C. Rapid evolution of animal mitochondrial DNA. Proc. Natl. Acad. Sci. USA. 1979;76(4):19671971. DOI 10.1073/pnas.76.4.1967.Derenko M., Denisova G., Malyarchuk B., Hovhannisyan A., Khachatryan Z., Hrechdakian P., Litvinov A., Yepiskoposyan L. Insights into matrilineal genetic structure, differentiation and ancestry of Armenians based on complete mitogenome data. Mol. Genet. Genom. 2019;294(6):1547-1559. DOI 10.1007/s00438-01901596-2.Derenko M., Denisova G., Malyarchuk B., Hovhannisyan A., Khachatryan Z., Hrechdakian P., Litvinov A., Yepiskoposyan L. Insights into matrilineal genetic structure, differentiation and ancestry of Armenians based on complete mitogenome data. Mol. Genet. Genom. 2019;294(6):1547-1559. DOI 10.1007/s00438-01901596-2.Derenko M.V., Malyarchuk B.A. Molecular Phylogeography of Populations of Northern Eurasia Based on Mitochondrial DNA Variability data. Magadan: SVNC DVO RAN, 2010. (in Russian)Derenko M.V., Malyarchuk B.A. Molecular Phylogeography of Populations of Northern Eurasia Based on Mitochondrial DNA Variability data. Magadan: SVNC DVO RAN, 2010. (in Russian)Elson J.L., Turnbull D.M., Howell N. Comparative genomics and the evolution of human mitochondrial DNA: assessing the effects of selection. Am. J. Hum. Genet. 2004;74(4):229-238. DOI 10.1086/381505.Elson J.L., Turnbull D.M., Howell N. Comparative genomics and the evolution of human mitochondrial DNA: assessing the effects of selection. Am. J. Hum. Genet. 2004;74(4):229-238. DOI 10.1086/381505.Eltsov N.P., Volodko N.V., Starikovskaya E.B., Mazunin I.O., Sukernik R.I. The role of natural selection in the evolution of mitochondrial haplogroups in Northeastern Eurasia. Rus. J. Genet. 2010; 46(9):1105-1107. DOI 10.1134/S1022795410090243.Eltsov N.P., Volodko N.V., Starikovskaya E.B., Mazunin I.O., Sukernik R.I. The role of natural selection in the evolution of mitochondrial haplogroups in Northeastern Eurasia. Rus. J. Genet. 2010; 46(9):1105-1107. DOI 10.1134/S1022795410090243.García Ó., Alonso S., Huber N., Bodner M., Parson W. Forensically relevant phylogeographic evaluation of mitogenome variation in the Basque Country. Forensic Sci. Int. Genet. 2020;46(5):102260. DOI 10.1016/j.fsigen.2020.102260.García Ó., Alonso S., Huber N., Bodner M., Parson W. Forensically relevant phylogeographic evaluation of mitogenome variation in the Basque Country. Forensic Sci. Int. Genet. 2020;46(5):102260. DOI 10.1016/j.fsigen.2020.102260.Giles R.E., Blanc H., Cann H.M., Wallace D.C. Maternal inheritance of human mitochondrial DNA. Proc. Natl. Acad. Sci. USA. 1980;77(11):6715-6719. DOI 10.1073/pnas.77.11.6715.Giles R.E., Blanc H., Cann H.M., Wallace D.C. Maternal inheritance of human mitochondrial DNA. Proc. Natl. Acad. Sci. USA. 1980;77(11):6715-6719. DOI 10.1073/pnas.77.11.6715.Ingman M., Gyllensten U. Rate variation between mitochondrial domains and adaptive evolution in humans. Hum. Mol. Genet. 2007; 16(19):2281-2287. DOI 10.1093/hmg/ddm180.Ingman M., Gyllensten U. Rate variation between mitochondrial domains and adaptive evolution in humans. Hum. Mol. Genet. 2007; 16(19):2281-2287. DOI 10.1093/hmg/ddm180.Kivisild T., Shen P., Wall D.P., Do B., Sung R., Davis K., Passarino G., Underhill P.A., Scharfe C., Torroni A., Scozzari R., Modiano D., Coppa A., de Knijff P., Feldman M., Cavalli-Sforza L.L., Oefner P.J. The role of selection in the evolution of human mitochondrial genomes. Genetics. 2006;172(1):373-387. DOI 10.1534/genetics.105.043901.Kivisild T., Shen P., Wall D.P., Do B., Sung R., Davis K., Passarino G., Underhill P.A., Scharfe C., Torroni A., Scozzari R., Modiano D., Coppa A., de Knijff P., Feldman M., Cavalli-Sforza L.L., Oefner P.J. The role of selection in the evolution of human mitochondrial genomes. Genetics. 2006;172(1):373-387. DOI 10.1534/genetics.105.043901.Kosakovsky Pond S.L., Frost S.D.W., Muse S.V. HyPhy: hypothesis testing using phylogenies. Bioinformatics. 2005;21(5):676-679. DOI 10.1093/bioinformatics/bti079.Kosakovsky Pond S.L., Frost S.D.W., Muse S.V. HyPhy: hypothesis testing using phylogenies. Bioinformatics. 2005;21(5):676-679. DOI 10.1093/bioinformatics/bti079.Librado P., Rozas J. DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics. 2009;25(11):14511452. DOI 10.1093/bioinformatics/btp187.Librado P., Rozas J. DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics. 2009;25(11):14511452. DOI 10.1093/bioinformatics/btp187.Litvinov A.N., Malyarchuk B.A., Derenko M.V. The nature of the molecular evolution of the mitochondrial genomes of the Russian population of East Europe. Vestnik Severo-Vostochnogo Nauchnogo Centra DVO RAN = The Bulletin of the North-East Scientific Center. 2020;2:107-113. DOI 10.34078/1814-0998-2020-2-107-113. (in Russian)Litvinov A.N., Malyarchuk B.A., Derenko M.V. The nature of the molecular evolution of the mitochondrial genomes of the Russian population of East Europe. Vestnik Severo-Vostochnogo Nauchnogo Centra DVO RAN = The Bulletin of the North-East Scientific Center. 2020;2:107-113. DOI 10.34078/1814-0998-2020-2-107-113. (in Russian)Liu J., Wang L.-D., Sun Y.-B., Li E.-M., Xu L.-Y., Zhang Y.-P., Yao Y.-G., Kong Q.-P. Deciphering the signature of selective constraints on cancerous mitochondrial genome. Mol. Biol. Evol. 2012; 29(4):1255-1261. DOI 10.1093/molbev/msr290.Liu J., Wang L.-D., Sun Y.-B., Li E.-M., Xu L.-Y., Zhang Y.-P., Yao Y.-G., Kong Q.-P. Deciphering the signature of selective constraints on cancerous mitochondrial genome. Mol. Biol. Evol. 2012; 29(4):1255-1261. DOI 10.1093/molbev/msr290.Malyarchuk B.A. Adaptive evolution signals in mitochondrial genes of Europeans. Biochemistry (Moscow). 2011;76(6):702-706. DOI 10.1134/S0006297911060113.Malyarchuk B.A. Adaptive evolution signals in mitochondrial genes of Europeans. Biochemistry (Moscow). 2011;76(6):702-706. DOI 10.1134/S0006297911060113.Mishmar D., Ruiz-Pesini E., Golik P., Macaulay V., Clark A.G., Hossei- ni S., Brandon M., Easley K., Chen E., Brown M.D., Sukernik R.I., Olckers A., Wallace D.C. Natural selection shaped regional mtDNA variation in humans. Proc. Natl. Acad. Sci. USA. 2003;100(1):171176. DOI 10.1073/pnas.0136972100.Mishmar D., Ruiz-Pesini E., Golik P., Macaulay V., Clark A.G., Hossei- ni S., Brandon M., Easley K., Chen E., Brown M.D., Sukernik R.I., Olckers A., Wallace D.C. Natural selection shaped regional mtDNA variation in humans. Proc. Natl. Acad. Sci. USA. 2003;100(1):171176. DOI 10.1073/pnas.0136972100.Murrell B., Moola S., Mabona A., Weighill T., Sheward D., Kosakovsky Pond S.L., Scheffler K. FUBAR: a fast, unconstrained bayesian approximation for inferring selection. Mol. Biol. Evol. 2013;30(5): 1196-1205. DOI 10.1093/molbev/mst030.Murrell B., Moola S., Mabona A., Weighill T., Sheward D., Kosakovsky Pond S.L., Scheffler K. FUBAR: a fast, unconstrained bayesian approximation for inferring selection. Mol. Biol. Evol. 2013;30(5): 1196-1205. DOI 10.1093/molbev/mst030.Murrell B., Wertheim J.O., Moola S., Weighill T., Scheffler K., Kosakovsky Pond S.L. Detecting individual sites subject to episodic diversifying selection. PLoS Genet. 2012;8(7):e1002764. DOI 10.1371/journal.pgen.1002764.Murrell B., Wertheim J.O., Moola S., Weighill T., Scheffler K., Kosakovsky Pond S.L. Detecting individual sites subject to episodic diversifying selection. PLoS Genet. 2012;8(7):e1002764. DOI 10.1371/journal.pgen.1002764.Olivieri A., Sidore C., Achilli A., Angius A., Posth C., Furtwängler A., Brandini S., Capodiferro M.R., Gandini F., Zoledziewska M., Pitzalis M., Maschio A., Busonero F., Lai L., Skeates R., Gradoli M.G., Beckett J., Marongiu M., Mazzarello V., Marongiu P., Rubino S., Rito T., Macaulay V., Semino O., Pala M., Abecasis G.R., Schlessinger D., Conde-Sousa E., Soares P., Richards M.B., Cucca F., Torroni A. Mitogenome diversity in Sardinians: a genetic window onto an Island’s past. Mol. Biol. Evol. 2017;34(5):1230-1239. DOI 10.1093/molbev/msx082.Olivieri A., Sidore C., Achilli A., Angius A., Posth C., Furtwängler A., Brandini S., Capodiferro M.R., Gandini F., Zoledziewska M., Pitzalis M., Maschio A., Busonero F., Lai L., Skeates R., Gradoli M.G., Beckett J., Marongiu M., Mazzarello V., Marongiu P., Rubino S., Rito T., Macaulay V., Semino O., Pala M., Abecasis G.R., Schlessinger D., Conde-Sousa E., Soares P., Richards M.B., Cucca F., Torroni A. Mitogenome diversity in Sardinians: a genetic window onto an Island’s past. Mol. Biol. Evol. 2017;34(5):1230-1239. DOI 10.1093/molbev/msx082.Ruiz-Pesini E., Mishmar D., Brandon M., Procaccio V., Wallace D.C. Effects of purifying and adaptive selection on regional variation in human mtDNA. Science. 2004;303(5655):223-226. DOI 10.1126/science.1088434.Ruiz-Pesini E., Mishmar D., Brandon M., Procaccio V., Wallace D.C. Effects of purifying and adaptive selection on regional variation in human mtDNA. Science. 2004;303(5655):223-226. DOI 10.1126/science.1088434.Skonieczna K., Malyarchuk B., Jawień A., Marszałek A., Banaszkiewicz Z., Jarmocik P., Grzybowski T. Mitogenomic differences be- tween the normal and tumor cells of colorectal cancer patients. Hum. Mutat. 2018;39(5):691-701. DOI 10.1002/humu.23402.Skonieczna K., Malyarchuk B., Jawień A., Marszałek A., Banaszkiewicz Z., Jarmocik P., Grzybowski T. Mitogenomic differences be- tween the normal and tumor cells of colorectal cancer patients. Hum. Mutat. 2018;39(5):691-701. DOI 10.1002/humu.23402.Stafford P., Chen-Quin E. The pattern of natural selection in somatic cancer mutations of human mtDNA. J. Hum. Genet. 2010;55(9): 605-612. DOI 10.1038/jhg.2010.76.Stafford P., Chen-Quin E. The pattern of natural selection in somatic cancer mutations of human mtDNA. J. Hum. Genet. 2010;55(9): 605-612. DOI 10.1038/jhg.2010.76.Sun C., Kong Q.-P., Zhang Y.-P. The role of climate in human mitochondrial DNA evolution: a reappraisal. Genomics. 2007;89(3): 338-342. DOI 10.1016/j.ygeno.2006.11.005.Sun C., Kong Q.-P., Zhang Y.-P. The role of climate in human mitochondrial DNA evolution: a reappraisal. Genomics. 2007;89(3): 338-342. DOI 10.1016/j.ygeno.2006.11.005.Wallace D.C. 1994 William Allan Award Address. Mitochondrial DNA variation in human evolution, degenerative disease, and aging. Am. J. Hum. Genet. 1995;57(2):201-223. PMCID PMC180 1540.Wallace D.C. 1994 William Allan Award Address. Mitochondrial DNA variation in human evolution, degenerative disease, and aging. Am. J. Hum. Genet. 1995;57(2):201-223. PMCID PMC180 1540.

The authors declare that there are no conflicts of interest present.