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La evolución, la evolución de las cosas. La humanización sistemática de los genes de la levadura revela funciones
Aashiq H Kachroo1, Jon M Laurent1, Christopher M Yellman1
1Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
Science (New York, N.Y.)
|May 23, 2015
Resumen
Las funciones esenciales de los genes se conservan a través de mil millones de años de evolución. Los genes humanos pueden reemplazar a los genes de la levadura, mostrando que las funciones conservadas se mantienen en vías biológicas específicas.
Área de la Ciencia:
- Biología evolutiva Biología evolutiva.
- Genética molecular genética molecular.
- La genómica es la genómica.
Sus antecedentes:
- Comprender la conservación de la función génica a través de vastas escalas de tiempo evolutivas es crucial para descifrar los principios evolutivos.
- Investigar la divergencia evolutiva profunda requiere examinar la compatibilidad funcional de los genes entre especies separadas por distancias evolutivas significativas.
Objetivo del estudio:
- Determinar si los genes conservan funciones ancestrales durante mil millones de años de evolución.
- Identificar los principios que rigen la divergencia evolutiva profunda mediante la evaluación de la conservación funcional.
- Explorar hasta qué punto los genes humanos pueden reemplazar funcionalmente los genes esenciales de la levadura.
Principales métodos:
- Reemplazó 414 genes esenciales de levadura con sus ortólogos humanos.
- Se analizó para la complementación de defectos letales de crecimiento tras la pérdida de genes de levadura.
- Utilizó simulaciones computacionales para confirmar el mantenimiento funcional a pesar de la divergencia de secuencias.
Principales resultados:
- Casi la mitad (47%) de los genes esenciales de la levadura podrían ser reemplazados funcionalmente por sus ortólogos humanos.
- La reemplazabilidad de genes no se predijo únicamente por la similitud de secuencias o los niveles de expresión.
- La reemplazabilidad dependía en gran medida de la participación del gen en módulos o vías biológicas específicas, como la biosíntesis de esteroles frente a la iniciación de la replicación del ADN.
Conclusiones:
- Las funciones ancestrales críticas de muchos genes esenciales se conservan durante mil millones de años de evolución.
- La conservación funcional se mantiene de una manera específica de la vía, lo que demuestra la resistencia a la secuencia, el empalme y la divergencia de la interfaz de proteínas.
- La selección para funciones biológicas específicas juega un papel clave en el mantenimiento de la reemplazabilidad de los genes a través del tiempo evolutivo profundo.
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