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El patrón de sustitución de nucleótidos en los principales loci del complejo de histocompatibilidad clase I revela

A L Hughes¹, M Nei

¹Center for Demographic and Population Genetics, University of Texas Health Science Center, Houston 77225.

|September 8, 1988

Resumen

La alta diversidad genética en el complejo mayor de histocompatibilidad (MHC) se explica por la selección sobredominante. Esta ventaja de los heterocigotos favorece diversos alelos del MHC, cruciales para la respuesta inmune.

Área de la Ciencia:

Inmunogenética La inmunogenética.
Biología evolutiva Biología evolutiva.
Genética molecular genética molecular.

Sus antecedentes:

El Complejo Mayor de Histocompatibilidad (MHC) exhibe un polimorfismo extremo en humanos y ratones.
La alta heterocigosidad (80-90%) en los loci de la CMH requiere una explicación.

Objetivo del estudio:

Para investigar los mecanismos evolutivos que impulsan el polimorfismo alto del MHC.
Para probar cuatro hipótesis: tasa de mutación, conversión génica, selección sobredominante y selección dependiente de la frecuencia.

Principales métodos:

Análisis de los patrones de sustitución de nucleótidos en los genes MHC de clase I en humanos y ratones.
Comparación de las tasas de sustitución en el sitio de reconocimiento de antígenos (ARS) frente a otras regiones de genes.

Principales resultados:

Las tasas de sustitución no sinónimas excedieron significativamente las tasas de sustitución sinónimas en la región ARS tanto en humanos como en ratones.
El patrón opuesto (sinónimos > no sinónimos) se observó en otras regiones de la CMH.

Conclusiones:

Los hallazgos apoyan fuertemente la hipótesis de la selección sobredominante (ventaja heterocigótica).
La ventaja de los heterocigotos es el principal impulsor del polimorfismo alto del MHC, mejorando la diversidad del sistema inmunológico.

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