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Trazar la historia evolutiva de la deleción CCR5delta32 a través de genomas antiguos y modernos
Kirstine Ravn1, Leonardo Cobuccio1, Rasa Audange Muktupavela2
1Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Cell
|May 6, 2025
Resumen
La variante CCR5-delta32, vinculada a la resistencia al VIH, se originó en Eurasia occidental hace más de 6.700 años. Esta eliminación genética experimentó una selección positiva, influyendo en su propagación y orientación terapéutica.
Área de la Ciencia:
- Genética de las poblaciones
- La evolución del hombre
- La genómica
Sus antecedentes:
- El alelo CCR5-delta32 está asociado con la resistencia al VIH-1 y tiene una historia evolutiva debatida, particularmente su frecuencia en las poblaciones europeas.
- Comprender el origen y la propagación de variantes genéticas como CCR5-delta32 es crucial para los estudios evolutivos y el desarrollo terapéutico.
Objetivo del estudio:
- Para aclarar la historia evolutiva y el origen espacio-temporal de la deleción CCR5-delta32.
- Investigar las presiones selectivas que actúan sobre el haplotipo CCR5-delta32.
- Explicar la presencia de CCR5-delta32 en América Latina y sus implicaciones para las terapias basadas en el receptor CCR5.
Principales métodos:
- Desarrolló un modelo probabilístico consciente del haplotipo utilizando 84 variantes preexistentes.
- Examinamos 934 genomas antiguos de baja cobertura para rastrear el origen de la deleción CCR5-delta32.
- Analizaron datos de ADN antiguos para identificar la selección positiva que actúa en el haplotipo CCR5-delta32.
Principales resultados:
- La deleción CCR5-delta32 se originó al menos hace 6.700 años en la estepa euroasiática occidental en un haplotipo específico.
- Fuerte evidencia de selección positiva en el haplotipo CCR5-delta32 en Eurasia occidental entre 8.000 y 2.000 años BP.
- La presencia de CCR5-delta32 en América Latina se atribuye a la mezcla genética poscolombina.
Conclusiones:
- El estudio proporciona una línea de tiempo evolutiva detallada para la deleción CCR5-delta32, que remonta sus raíces a la antigua Eurasia Occidental.
- La selección positiva moldeó significativamente la distribución del haplotipo CCR5-delta32.
- Las complejas relaciones genotipo- haplotipo- fenotipo requieren una cuidadosa consideración para las estrategias terapéuticas dirigidas al CCR5.
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