Bulletin of the American Physical Society
APS March Meeting 2011
Volume 56, Number 1
Monday–Friday, March 21–25, 2011; Dallas, Texas
Abstract: S1.00141 : The Heterogeneity of Mutational Tolerance in a Protein is Dependent on the Strength of Selective Pressure Correlating with Sectors of Co-evolving Residues
Author:
Proteins are capable of tolerating mutations at many positions
while still maintaining fold and function. Previous studies have failed to
consider how tolerance to random mutagenesis might depend on the strength of
selective pressure. To examine this, we measured the fitness of every single
point mutation of TEM-1 beta-lactamase across a range of ampicillin
concentrations utilizing a novel application of deep-sequencing. We found
that the relative mutational robustness between positions varied
considerably with respect to ampicillin concentration: at a low ampicillin
concentration only a few positions are intolerant of mutations, while at a
higher ampicillin concentration many additional positions are as equally
intolerant of mutations. Using an analytic method termed statistical
coupling analysis (SCA) to measure the co-variation between all positions in
a sequence alignment of beta-lactamases revealed sectors of co-evolving
positions associated with groups of residues having increased sensitivity to
mutagenesis at either low or high ampicillin concentrations. Our findings
suggest that nature has ``designed'' proteins to be robust to random
mutagenesis by loading the constraints for fitness on discrete networks of
co-evolving positions depending on the strength of selective
pressure.
To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2011.MAR.S1.141
Follow Us |
Engage
Become an APS Member |
My APS
Renew Membership |
Information for |
About APSThe American Physical Society (APS) is a non-profit membership organization working to advance the knowledge of physics. |
© 2021 American Physical Society
| All rights reserved | Terms of Use
| Contact Us
Headquarters
1 Physics Ellipse, College Park, MD 20740-3844
(301) 209-3200
Editorial Office
1 Research Road, Ridge, NY 11961-2701
(631) 591-4000
Office of Public Affairs
529 14th St NW, Suite 1050, Washington, D.C. 20045-2001
(202) 662-8700