Un equipo investigador de la Universidad de Oregón ha descubierto que la evolución no puede nunca ir hacia atrás, ya que los pasos hacia los genes presentes en nuestros antecesores quedan bloqueados para siempre. Los hallazgos, el resultado del primer estudio riguroso sobre evolución inversa a nivel molecular, aparecen en el número de 24 de septiembre de Nature.El equipo investigador, liderado por Joe Thornton, profesor in the Center for Ecology and Evolutionary Biology de la Universidad de oregón y el Howard Hughes Medical Institute, ha resucitado y manipulado el gen de un receptor hormonal clave tal como existió hace más de 400 millones de años en nuestros ancestros vertebrados más antiguos. Para ello ha empleado la reconstrucción por ordenador de secuencias de genes ancestrales, síntesis de ADN, ingeniería proteínica y cristalografía de rayos X. Encontraron que en un intervalo de tiempo muy corto, se produjeron 5 mutaciones aleatorias que causaron sutiles modificaciones en la estructura roteínica, y que eran totalmente incompatibles con la forma primordial del receptor. El descubrimiento de esta quema de naves por la evolución, significa que las formas de vida actuales de la Tierra, podrían no ser ni ideales ni inevitables.
El trabajo se centra en la evolución de una proteína denominada receptor glucocorticoid (GR), que se une a la hormona cortisol y regular la respuesta al estrés, la inmunidad, el metabolismo y el comportamiento en humanos y otros vertebrados.
La irreversibilidad evolutiva del GR sugiere que las moléculas que regulan hoy nuestra biología podrían no ser productos inevitables del proceso evolutivo. Según Thornton "Las mutaciones restrictivas en el GR eliminaron algunas de las condiciones que se abrían inicialmente a la forma ancestral como posibilidades evolutivas. Es probable que a lo largo de la historia, se hayan producido otras mutaciones restrictivas, que han cerrado innumerables caminos que podría haber seguido la evolución"
A University of Oregon research team has found that evolution can never go backwards, because the paths to the genes once present in our ancestors are forever blocked. The findings -- the result of the first rigorous study of reverse evolution at the molecular level -- appear in the Sept. 24 issue of Nature.The team, led by Joe Thornton, a professor in the UO's Center for Ecology and Evolutionary Biology and the Howard Hughes Medical Institute, used computational reconstruction of ancestral gene sequences, DNA synthesis, protein engineering and X-ray crystallography to resurrect and manipulate the gene for a key hormone receptor as it existed in our earliest vertebrate ancestors more than 400 million years ago. They found that over a rapid period of time, five random mutations made subtle modifications in the protein's structure that were utterly incompatible with the receptor's primordial form. The discovery of evolutionary bridge burning implies that today's versions of life on Earth may be neither ideal nor inevitable.
The work is focused on the evolution of a protein called the glucocorticoid receptor (GR), which binds the hormone cortisol and regulates the stress response, immunity, metabolism and behavior in humans and other vertebrates.
GR's evolutionary irreversibility suggests that the molecules that drive our biology today may not be inevitable products of the evolutionary process. "In the GR's case, restrictive mutations erased the conditions that previously opened up the ancestral form as an evolutionary possibility. It's likely that throughout history other kinds of restrictive mutations have taken place, closing off innumerable trajectories that evolution might otherwise have taken," Thornton speculated.
Tomado de/Taken from Experientia docet/Science Daily
Resumen de la publicación/Abstract of the paper
An epistatic ratchet constrains the direction of glucocorticoid receptor evolution
Jamie T. Bridgham, Eric A. Ortlund & Joseph W. Thornton
Nature 461, 515-519 (24 September 2009)
doi:10.1038/nature08249
Abstract
The extent to which evolution is reversible has long fascinated biologists. Most previous work on the reversibility of morphological and life-history evolution has been indecisive, because of uncertainty and bias in the methods used to infer ancestral states for such characters. Further, despite theoretical work on the factors that could contribute to irreversibility, there is little empirical evidence on its causes, because sufficient understanding of the mechanistic basis for the evolution of new or ancestral phenotypes is seldom available. By studying the reversibility of evolutionary changes in protein structure and function, these limitations can be overcome. Here we show, using the evolution of hormone specificity in the vertebrate glucocorticoid receptor as a case-study, that the evolutionary path by which this protein acquired its new function soon became inaccessible to reverse exploration. Using ancestral gene reconstruction, protein engineering and X-ray crystallography, we demonstrate that five subsequent 'restrictive' mutations, which optimized the new specificity of the glucocorticoid receptor, also destabilized elements of the protein structure that were required to support the ancestral conformation. Unless these ratchet-like epistatic substitutions are restored to their ancestral states, reversing the key function-switching mutations yields a non-functional protein. Reversing the restrictive substitutions first, however, does nothing to enhance the ancestral function. Our findings indicate that even if selection for the ancestral function were imposed, direct reversal would be extremely unlikely, suggesting an important role for historical contingency in protein evolution.
