vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ16.196vavilov-852Research ArticleSNP-маркеры в биомедицинеSNP markers in biomedicineКандидатные SNP-маркеры социального доминирования, способные влиять на сродство ТАТА-связывающего белка к промоторам генов человекаCandidate SNP markers of social dominance, which may affect the affinity of the TATAbinding protein for human gene promotersЧадаеваИ. В.ChadaevaI. V.

Новосибирск, Россия

Novosibirsk, Russia

РассказовД. А.RasskazovD. A.

Новосибирск, Россия

Novosibirsk, Russia

ШарыповаЕ. Б.SharypovaE. B.

Новосибирск, Россия

Novosibirsk, Russia

СавинковаЛ. К.SavinkovaL. K.

Новосибирск, Россия

Novosibirsk, Russia

ПономаренкоП. М.PonomarenkoP. M.

США

USA

ПономаренкоМ. П.PonomarenkoM. P.

Новосибирск, Россия

Novosibirsk, Russia

pon@bionet.nsc.ruФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»РоссияInstitute of Cytology and Genetics SB RASRussian FederationДетский Госпиталь Лос-Анжелеса, Университет Южной КалифорнииСоединённые Штаты АмерикиChildren’s Hospital Los Angeles, University of Southern CaliforniaUnited StatesФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук» Федеральное государственное автономное образовательное учреждение высшего образования «Новосибирский национальный исследовательский государственный университет»РоссияInstitute of Cytology and Genetics SB RAS Novosibirsk State UniversityRussian Federation201602022017206787796Copyright © Чадаева И.В., Рассказов Д.А., Шарыпова Е.Б., Савинкова Л.К., Пономаренко П.М., Пономаренко М.П., 20172017Чадаева И.В., Рассказов Д.А., Шарыпова Е.Б., Савинкова Л.К., Пономаренко П.М., Пономаренко М.П.Chadaeva I.V., Rasskazov D.A., Sharypova E.B., Savinkova L.K., Ponomarenko P.M., Ponomarenko M.P.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/852

Предложена эвристическая гипотеза, согласно которой, если избыток какого-либо белка в ряде органов животных был экспериментально установлен как физиологический маркер повышенной агрессивности и если некоторый полиморфизм (SNP) человека вызывает суперэкспрессию гена, гомологичного гену этого белка у животных, то этот полиморфизм может быть кандидатным SNP-маркером предрасположенности к социальному доминированию, тогда как случаю дефицитной экспрессии может соответствовать социальное подчинение и наоборот. В рамках этой гипотезы проанализировали 21 ген человека: ADORA2A, BDNF, CC2D1A, CC2D1B, ESR2, FEV, FOS, GH1, GLTSCR2, GRIN1, HTR1B, HTR1A, HTR2A, HTR2C, LGI4, LEP, MAOA, SLC17A7, SLC6A3, SNCA, TH, – которые представляют функции белков, известных как физиологические маркеры агрессивного поведения животных: гормоны и их рецепторы, ферменты биосинтеза и рецепторы нейромедиаторов, транскрипционные и нейротропные факторы. Эти белки могут играть важную роль при установлении иерархических отношений у социальных видов животных. С использованием созданного нами ранее Web-сервиса SNP_TATA_Comparator (http://beehive.bionet.nsc.ru/cgi-bin/mgs/tatascan/start.pl) мы проанализировали 381 SNP в районе [–70;–20] перед стартами белок-кодирующих транскриптов (район связывания ТАТА-связывающего белка, ТВР) из базы данных dbSNP (выпуск № 147). Было найдено 45 и 47 кандидатных SNP-маркеров доминирования и подчинения соответственно (например, rs373600960 и rs747572588). В рамках предложенной эвристической гипотезы и выпуска № 147 базы данных dbSNP мы получили статистически достоверные (α < 10–5) свидетельства о действии естественного отбора как против дефицитной экспрессии генов, способных влиять на предрасположенность к доминированию, так и в пользу того, что подчинение и доминирование могут характеризовать норму реакции агрессивности (отличие незначимо: α > 0.35). Предложенная гипотеза, выявленные на ее основе кандидатные SNP-маркеры и закономерности их влияния естественного отбора на геном человека обсуждаются в контексте литературных данных: могут ли они иметь какое-либо отношение к социальному доминированию у людей. Сделано заключение – эти результаты нуждаются в экспериментальной проверке.

The following heuristic hypothesis has been proposed: if an excess of a protein in several animal organs was experimentally identified as physiological marker of increased aggressiveness and if a polymorphism (SNP) can cause superexpression of the human gene homologous of the animal gene encoding this protein, then this polymorphism can be a candidate SNP marker of social dominance, whereas a deficient expression corresponds to subordinate and vice versa. Within this hypothesis, we analyzed 21 human genes –ADORA2A, BDNF, CC2D1A, CC2D1B, ESR2, FEV, FOS, GH1, GLTSCR2, GRIN1, HTR1B, HTR1A, HTR2A, HTR2C, LGI4, LEP, MAOA, SLC17A7, SLC6A3, SNCA, TH – which represent the functions of proteins known as physiological markers of aggressive behavior in animals: hormones and their receptors, biosynthetic enzymes and receptors of neurotransmitters, transcription and neurotrophic factors. These proteins may play an important role in determining hierarchical relationships in social animals. Using our previously developed Web-service SNP_TATA_Comparator (http://beehive.bionet.nsc.ru/cgi-bin/mgs/tatascan/start.pl), we analyzed 381 SNPs within the region of [–70; –20] relative to the start protein-coding transcripts, which is the region of the all known TATA-binding protein (TBP) binding sites. We took them from the database dbSNP, v.147 As a result, we found 45 and 47 candidate SNP markers of dominance and submission, respectively (e. g., rs373600960 and rs747572588). Within the framework of the proposed heuristic hypotheses and database dbSNP v.147, we found statistically significant (α < 10-5) evidence of the effects of natural selection against the deficient expression of genes, which can affect the predisposition to dominate, as well as in favor of both subordination and domination behavior as a norm of reaction of aggressiveness (difference not significant: α > 0.35). The proposed hypothesis, the candidate SNP markers predicted and the observed regularities of effects of natural selection for the human genome are discussed in comparison with published data: whether they can have any relation to social dominance in human. It was concluded that these results require experimental verification.

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