[extropy-chat] PAPER: Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins

[mike99]

Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter
Proteins
Daniel M. Weinreich,* Nigel F. Delaney, Mark A. DePristo, Daniel L. Hartl

Five point mutations in a particular ß-lactamase allelejointly increase
bacterial resistance to a clinically importantantibiotic by a factor of
100,000. In principle, evolution tothis high-resistance ß-lactamase might
follow anyof the 120 mutational trajectories linking these alleles.
However,we demonstrate that 102 trajectories are inaccessible to Darwinian
selection and that many of the remaining trajectories have negligible
probabilities of realization, because four of these five mutations fail to
increase drug resistance in some combinations. Pervasive biophysical
pleiotropy within the ß-lactamase seems to be responsible, and because such
pleiotropy appears to be a general property of missense mutations, we
conclude that much protein evolution will be similarly constrained. This
implies that the protein tape of life may be largely reproducible and even
predictab.

Abstract and Full text Links at Science
http://www.sciencemag.org/cgi/content/abstract/312/5770/111


Regards,

Michael LaTorra

mike99 at lascruces.com
mlatorra at nmsu.edu