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La evolución de la especificidad del ADN en una familia de factores de transcripción produjo un nuevo módulo

Alesia N McKeown¹, Jamie T Bridgham¹, Dave W Anderson¹

¹Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403, USA.

|September 27, 2014

Resumen

Se estudió la evolución de la especificidad de unión del factor de transcripción al ADN en los receptores de hormonas esteroideas. Las mutaciones clave debilitaron la unión al ADN ancestral al tiempo que permitieron el reconocimiento de nuevas secuencias, revelando determinantes negativos en la evolución de la especificidad.

Área de la Ciencia:

Biología Molecular Biología Molecular
Biología evolutiva Biología evolutiva.
La bioquímica es la bioquímica.

Sus antecedentes:

Los factores de transcripción (TF) regulan las redes de genes mediante la unión de secuencias específicas de ADN.
Comprender la evolución de la especificidad de unión del ADN TF es crucial para descifrar la regulación génica.
La familia de los receptores de la hormona esteroide (SR) proporciona un modelo para el estudio de la evolución de la TF.

Objetivo del estudio:

Para investigar cómo el reconocimiento del ADN se diversificó dentro de la familia de los receptores de la hormona esteroide (SR).
Aclarar los mecanismos moleculares subyacentes a la evolución de la nueva especificidad de unión al ADN TF.

Principales métodos:

Análisis filogenético para rastrear la historia evolutiva.
Pruebas bioquímicas para medir la afinidad y la especificidad de unión al ADN.
Técnicas biofísicas para sondear las interacciones moleculares entre los TF y el ADN.

Principales resultados:

Tres mutaciones específicas en una copia del gen SR debilitaron la unión al elemento de respuesta al estrógeno ancestral (ERE).
Estas mutaciones aumentaron simultáneamente la unión a los nuevos elementos de respuesta esteroide (ESR).
Los determinantes negativos (interacciones desfavorables) y las sustituciones permisivas fueron fundamentales para alterar la selectividad del ADN y la afinidad de unión.

Conclusiones:

Los determinantes negativos de la unión al ADN juegan un papel importante en la selectividad de la secuencia TF.
La evolución de la nueva especificidad de unión al ADN TF puede ocurrir sin interrumpir los módulos reguladores ancestrales.
Este estudio aclara un mecanismo para la coevolución de la unión al ADN TF y la especificidad del ligando.

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