Seleção evolucionária entre modos alternativos de regulação de genes

Evolutionary selection between alternative modes of gene regulation

Ulrich Gerlanda,1 and Terence Hwab,1

+Author Affiliations

aInstitute for Theoretical Physics, Arnold Sommerfeld Center for Theoretical Physics, Theresienstrasse 37, 80333 Munich, Germany; and

bCenter for Theoretical Biological Physics and Department of Physics, University of California at San Diego, La Jolla, CA 92093-0374

Edited by Curtis G. Callan, Jr., Princeton University, Princeton, NJ, and approved April 2, 2009 (received for review August 27, 2008)

Abstract

Microorganisms employ a wealth of gene regulatory mechanisms to adjust their growth programs to variations in the environment. It was pointed out long ago [Savageau M (1977) Proc Natl Acad Sci USA 74: 5647–5651] that the particular mode of gene regulation employed may be correlated with the “demand” on the regulated gene, i.e., how frequently the gene product is needed in its natural habitat. An evolutionary “use-it-or-lose-it” principle was proposed to govern the choice of gene regulatory strategies. Here, we examine quantitatively the forces selecting for and against two opposing modes of gene regulation, in the context of an evolutionary model that takes genetic drift, mutation, and time-dependent selection into account. We consider the effect of time-dependent selection, with periods of strong selection alternating with periods of neutral evolution. Using a variety of analytical methods, we find the effective population size and the typical time scale of environmental variations to be key parameters determining the fitness advantage of the different modes of regulation. Our results support Savageau's use-it-or-lose-it principle for small populations with long time scales of environmental variations and support a complementary “wear-and-tear” principle for the opposite situation.

transcription control design principles molecular evolution time-dependent selection
Footnotes

1To whom correspondence may be addressed. E-mail: gerland@lmu.de or hwa@ucsd.edu.
Author contributions: U.G. and T.H. designed research, performed research, and wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0808500106/DCSupplemental.

↵† Activating and repressing TFs in bacteria do not differ in size, length of binding sequence, or other obvious properties that would significantly affect the mutation rates. The robustness of the model behavior against small differences in the mutation rates is addressed below.

↵‡ For a low-demand situation, this corresponds to the selection sact on the activator, whereas it corresponds to the selection srep on the repressor in a high-demand situation

↵§ Note that in a strict sense, the validity of the 2-state approximation breaks down when the distribution of x is no longer peaked at the boundaries, i.e., as we approach the deterministic limit. However, it nevertheless yields a useful estimate for the phase boundary.

+++++

PDF gratuito do artigo aqui.