Аннотация

Развитие методов генного и геномного редактирования повышает актуальность прогноза и уменьшения вероятности нецелевых, плейотропных последствий. Одним из таких направлений может быть оценка структурно-функциональных особенностей геномных мишеней редактирования по наиболее полиморфным геномным элементам, таким как транспозоны. Цель исследования – выявить распределения транспозонов в генах, наиболее часто выбираемых в качестве мишеней генного редактирования, и на их флангах у разных видов млекопитающих. Исследование выполнялось на геномных последовательностях человека (Homo sapiens), крупного рогатого скота (Bos taurus), домашнего кролика (Oryctolagus cuniculus) и домовой мыши (Mus musculus) белок-кодирующих генов миостатина (mstn), меланофилина (mlph), рецептора лептина (lepr), белка ремоделинга хроматина (хромосома Х, atrx), генов эволюционно консервативной петли хроматина (фактор регуляции транскрипции – auts2, N-ацетилгалактозаминилтрансфераза – galnt17, кальций связывающий белок 1 – caln1), а также их флангов. Распределение транспозонов оценивали с использованием программы RepeatMasker, статистическую обработку выполняли с применением программы Jamovi. Рассматривались следующие генные и геномные особенности: частота встречаемости разных типов диспергированных повторов, доминирующих у предковых видов млекопитающих и затем вытесненных молодыми вариантами; зависимость частоты встречаемости разных повторов от локализации в аутосомах и хромосоме Х, функциональной принадлежности групп генов, их локализации в общей и разных хромосомах, перекрывания генов. Выявлены отличия по частотам встречаемости «древних» и «молодых» транспозонов между человеком, крупным рогатым скотом и грызунами, по-видимому, связанные с разной скоростью смены поколений; обнаружены ассоциации между функциями белков и консервативностью генетического сцепления между кодирующими их генами; генетически сцепленные гены у разных видов отличались по обогащенности «древними» транспозонами, что, предположительно, ассоциировано с видоспецифичными различиями в защищенности от транспозиций соответствующих геномных районов. Полученные данные о видо- и ген-специфичных особенностях распределения транспозонов необходимо учитывать в целях предупреждения нежелательных эффектов редактирования соответствующих геномных районов.

Ключевые слова

Генное редактирование, генетическое сцепление, хроматиновая петля, эволюционная консервативность, «древние» и «молодые» транспозоны, человек, крупный рогатый скот, домашний кролик, домовая мышь

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