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RoAM: reconstrucción computacional de metilomas antiguos y identificación de regiones diferencialmente metiladas
Yoav Mathov1,2, Naomi Rosen1, Chen Leibson1
1Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, the Hebrew University of Jerusalem, Jerusalem, 9190401, Israel.
Genome biology
|September 4, 2025
Resumen
Mejoramos el software RoAM (reconstrucción de la metilación antigua) para el análisis de la metilación del ADN antiguo. Nuestro estudio revela cambios en la dieta que afectan los genes del metabolismo del azúcar y la regulación de la insulina después de la transición neolítica en los Balcanes.
Área de la Ciencia:
- La paleogenómica
- La epigenética
- Análisis de ADN antiguo
Sus antecedentes:
- La metilación del ADN antiguo (epigenética) proporciona información sobre los procesos biológicos pasados.
- La reconstrucción de los metilomas antiguos es crucial para comprender los cambios evolutivos e históricos.
- Las herramientas anteriores carecían de la flexibilidad y la confiabilidad para estudios paleoepigenómicos integrales.
Objetivo del estudio:
- Introducir una versión mejorada del software RoAM (reconstrucción de la metilación antigua).
- Permitir una reconstrucción robusta de los metilomas antiguos y la identificación de las regiones diferencialmente metiladas (DMR).
- Investigar los cambios epigenéticos asociados con la transición neolítica en las poblaciones balcánicas.
Principales métodos:
- Utilizando una refinada tubería de RoAM con filtrado avanzado y control de calidad.
- Aplicación de la herramienta RoAM mejorada a muestras de ADN antiguas de poblaciones balcánicas pre y post-neolíticas.
- Realizar análisis de metilación diferencial para identificar las DMR en los genes relevantes.
Principales resultados:
- La herramienta RoAM mejorada generó con éxito mapas de metilación de ADN antiguos de alta calidad.
- Se identificaron DMR significativas en los genes asociados con el metabolismo del azúcar entre las muestras pre y post-neolíticas.
- Se observó hipermetilación post-neolítica de PTPRN2, un gen que regula la secreción de insulina.
Conclusiones:
- El RoAM mejorado es una herramienta poderosa para la paleoepigenómica.
- Los cambios en la dieta durante la transición neolítica influyeron en la regulación epigenética del metabolismo.
- La evidencia sugiere un potencial hipoinsulinismo en las poblaciones de cazadores-recolectores pre-neolíticos.
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