vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ21.006vavilov-2915Research ArticleБИОИНФОРМАТИКА И СИСТЕМНАЯ КОМПЬЮТЕРНАЯ БИОЛОГИЯBIOINFORMATICS AND COMPUTATIONAL SYSTEMS BIOLOGYФилостратиграфический анализ генных сетей заболеваний человекаPhylostratigraphic analysis of gene networks of human diseaseshttps://orcid.org/0000-0003-2724-4497МустафинЗ. С.MustafinZ. S.

Новосибирск

Novosibirsk

mustafinzs@bionet.nsc.ruhttps://orcid.org/0000-0003-3138-381XЛашинС. А.LashinS. A.

Новосибирск

Novosibirsk

https://orcid.org/0000-0001-7754-8611МатушкинЮ. Г.MatushkinYu. G.

Новосибирск

Novosibirsk

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityRussian Federation2021150320212514656Copyright © Мустафин З.С., Лашин С.А., Матушкин Ю.Г., 20212021Мустафин З.С., Лашин С.А., Матушкин Ю.Г.Mustafin Z.S., Lashin S.A., Matushkin Y.G.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/2915

Филостратиграфический анализ – это подход к исследованию эволюции генов, позволяющий определить время возникновения генов за счет анализа филогенетических деревьев организмов, обладающих ортологичными к исследуемому генами. Такой анализ может открыть важные этапы в эволюции как организма в целом, так и групп функционально связанных генов, в частности генных сетей. В дополнение к исследованию времени возникновения гена изучается уровень его генетической изменчивости и то, какому типу отбора подвержен ген по отношению к наиболее близкородственным организмам. С помощью приложения Orthoscape были проанализированы генные сети из базы данных KEGG Pathway, Human Diseases, ассоциированные с заболеваниями человека. Выявлено, что большинство генов, описанных в генных сетях, подвержены стабилизирующему отбору, обнаружена высокая достоверная корреляция между временем возникновения гена и уровнем генетической изменчивости, которой он подвержен, – чем моложе ген, тем выше уровень генетической изменчивости. Было также показано, что среди проанализированных генных сетей наибольшая доля эволюционно молодых генов обнаружена в сетях, связанных с заболеваниями иммунной системы (65 %), а эволюционно древних генов – в сетях, ответственных за формирование зависимостей человека от веществ, вызывающих привыкание к химическим соединениям (88 %); генные сети, связанные с развитием инфекционных заболеваний, вызванных паразитами, достоверно обогащены эволюционно молодыми генами, а генные сети, ответственные за развитие специфических типов рака, – эволюционно древними генами.

Phylostratigraphic analysis is an approach to the study of gene evolution that makes it possible to determine the time of the origin of genes by analyzing their orthologous groups. The age of a gene belonging to an orthologous group is def ined as the age of the most recent ancestor of all species represented in that group. Such an analysis can reveal important stages in the evolution of both the organism as a whole and groups of functionally related genes, in particular gene networks. In addition to investigating the time of origin of a gene, the level of its genetic variability and what type of selection the gene is subject to in relation to the most closely related organisms is studied. Using the Orthoscape application, gene networks from the KEGG Pathway, Human Diseases database describing various human diseases were analyzed. It was shown that the majority of genes described in gene networks are under stabilizing selection and a high reliable correlation was found between the time of gene origin and the level of genetic variability: the younger the gene, the higher the level of its variability is. It was also shown that among the gene networks analyzed, the highest proportion of evolutionarily young genes was found in the networks associated with diseases of the immune system (65 %), and the highest proportion of evolutionarily ancient genes was found in the networks responsible for the formation of human dependence on substances that cause addiction to chemical compounds (88 %); gene networks responsible for the development of infectious diseases caused by parasites are signif icantly enriched for evolutionarily young genes, and gene networks responsible for the development of specif ic types of cancer are signif icantly enriched for evolutionarily ancient genes.

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