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Evolución reguladora de la inmunidad innata a través de la cooptación de retrovirus endógenos
Edward B Chuong1, Nels C Elde2, Cédric Feschotte2
1Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Science (New York, N.Y.)
|March 5, 2016
Resumen
Los retrovirus endógenos (ERV) han dado forma a las defensas inmunitarias de los mamíferos al proporcionar nuevos potenciadores de la transcripción para la respuesta al interferón. Estas secuencias virales son cruciales para la inmunidad innata y la innovación genética.
Área de la Ciencia:
- La genómica
- Inmunología
- Biología evolutiva
Sus antecedentes:
- Los retrovirus endógenos (ERV) son frecuentes en los genomas de los mamíferos y poseen elementos reguladores de la transcripción.
- El papel de la propagación de ERV en la evolución de la regulación génica no se entiende bien.
Objetivo del estudio:
- Investigar el impacto de los ERV en la evolución de la regulación génica, específicamente dentro de la red de respuesta al interferón (IFN).
- Determinar la importancia funcional de los potenciadores derivados del ERV en la inmunidad innata de los mamíferos.
Principales métodos:
- Genómica comparativa para identificar los ERV específicos del linaje y su distribución.
- Edición del gen CRISPR-Cas9 en células humanas para eliminar elementos de ERV.
- Análisis de los cambios en la expresión génica en respuesta a la estimulación de IFN y la activación del inflamatorio.
Principales resultados:
- Los ERV han influido significativamente en la evolución de la red transcripcional de respuesta IFN en diversos linajes de mamíferos.
- Los ERV específicos de linaje han dispersado independientemente numerosos potenciadores inducibles por IFN.
- La eliminación de los elementos ERV en humanos alteró la expresión de los genes inducidos por IFN y afectó la activación del inflamatorio AIM2.
Conclusiones:
- Los ERV sirven como un reservorio de secuencias reguladoras que mejoran la respuesta del sistema inmune innato a los interferones.
- Estos antiguos elementos virales contribuyen a la innovación genética y a la evolución de las defensas inmunes de los mamíferos.
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