Кандидатные SNP-маркеры социального доминирования, способные влиять на сродство ТАТА-связывающего белка к промоторам генов человека

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.

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