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Вавиловский журнал генетики и селекции

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Технологии поиска и исследования потенциально осциллирующих ферментативных систем

https://doi.org/10.18699/VJ21.035

Полный текст:

Аннотация

Многие процессы в живых организмах подвержены периодическим колебаниям на различных иерархических уровнях их организации: от молекулярного-генетического до популяционного и экологического. Осциллирующие процессы отвечают за клеточные циклы как у прокариот, так и у эукариот, за циркадные ритмы, синхронную связь дыхания с сердечными сокращениями и др. Колебания численностей организмов в природных популяциях могут быть обусловлены собственными свойствами популяций, их возрастной структурой, а также экологическими взаимоотношениями с другими видами. Наряду с экспериментальными подходами, для исследования осциллирующих биологических систем широко применяется математическое и компьютерное моделирование. В данной статье представлены классические математические модели, которые описывают осциллирующее поведение в биологических системах. Приведены методы поиска осциллирующих молекулярно-генетических систем на примере их частного случая – осциллирующих ферментативных систем. Рассмотрены факторы, влияющие на циклическую динамику в живых системах, характерные не только для молекулярно-генетического уровня, но и для более высоких уровней организации. Обсуждается применение различных способов описания генных сетей для моделирования осциллирующих молекулярно-генетических систем, где важнейшим фактором возникновения циклического поведения является наличие обратных связей. Представлены технологии поиска потенциально осциллирующих ферментативных систем. С помощью метода, описанного в статье, проводится поэтапный процесс построения и анализа сначала структурных моделей (графов) генных сетей, а затем реконструкции математических моделей и вычислительных экспериментов с ними. Структурные модели идеально подходят для задач автоматического поиска потенциальных осциллирующих контуров (связных подграфов), структура которых может соответствовать математической модели молекулярно-генетической системы, демонстрирующей осциллирующее поведение в динамике. При этом именно численное исследование математических моделей для отобранных контуров позволяет подтвердить наличие в них устойчивых предельных циклов. В качестве примера применения технологии проанализирована сеть из 300 метаболических реакций бактерии Escherichia coli с использованием инструментов математического и компьютерного моделирования. В частности, показано осциллирующее поведение для контура, реакции которого входят в путь биосинтеза триптофана.

Об авторах

Т. Н. Лахова
Курчатовский геномный центр ИЦиГ СО РАН
Россия

Новосибирск



Ф. В. Казанцев
Курчатовский геномный центр ИЦиГ СО РАН
Россия

Новосибирск



С. А. Лашин
Курчатовский геномный центр ИЦиГ СО РАН; Новосибирский национальный исследовательский государственный университет
Россия

Новосибирск



Ю. Г. Матушкин
Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университет
Россия

Новосибирск



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