Selection Intensity Against Deleterious Mutations in RNA Secondary Structures and Rate of Compensatory Nucleotide Substitutions

Corresponding author: Wolfgang Stephan, Department of Evolutionary Biology, University of Munich, Luisenstrasse 14, 80333 Munich, Germany., stephan{at}zi.biologie.uni-muenchen.de (E-mail)

Communicating editor: G. B. GOLDING

A two-locus model of reversible mutations with compensatory fitness interactions is presented; single mutations are assumed to be deleterious but neutral in appropriate combinations. The expectation of the time of compensatory nucleotide substitutions is calculated analytically for the case of tight linkage between sites. It is shown that selection increases the substitution time dramatically when selection intensity Ns > 1, where N is the diploid population size and s the selection coefficient. Computer simulations demonstrate that recombination increases the substitution time, but the effect of recombination is small when selection is weak. The amount of linkage disequilibrium generated in the process of compensatory substitution is also investigated. It is shown that significant linkage disequilibrium is expected to be rare in natural populations. The model is applied to the mRNA secondary structure of the bicoid 3' untranslated region of Drosophila. It is concluded that average selection intensity Ns against single deleterious mutations is not likely to be much larger than 1.

This article has been cited by other articles:

				J. L. Knies, K. K. Dang, T. J. Vision, N. G. Hoffman, R. Swanstrom, and C. L. Burch Compensatory Evolution in RNA Secondary Structures Increases Substitution Rate Variation among Sites Mol. Biol. Evol., August 1, 2008; 25(8): 1778 - 1787. [Abstract] [Full Text] [PDF]

				K. R. Takahasi and H. Innan The Direction of Linkage Disequilibrium: A New Measure Based on the Ancestral-Derived Status of Segregating Alleles Genetics, July 1, 2008; 179(3): 1705 - 1712. [Abstract] [Full Text] [PDF]

				K. M. Teshima and H. Innan Neofunctionalization of Duplicated Genes Under the Pressure of Gene Conversion Genetics, March 1, 2008; 178(3): 1385 - 1398. [Abstract] [Full Text] [PDF]

				S. A. Shabalina, A. Y. Ogurtsov, and N. A. Spiridonov A periodic pattern of mRNA secondary structure created by the genetic code. Nucleic Acids Res., January 1, 2006; 34(8): 2428 - 2437. [Abstract] [Full Text] [PDF]

				Y. Iwasa, F. Michor, and M. A. Nowak Stochastic Tunnels in Evolutionary Dynamics Genetics, March 1, 2004; 166(3): 1571 - 1579. [Abstract] [Full Text] [PDF]

				J. F. Baines, J. Parsch, and W. Stephan Pleiotropic Effect of Disrupting a Conserved Sequence Involved in a Long-Range Compensatory Interaction in the Drosophila Adh Gene Genetics, January 1, 2004; 166(1): 237 - 242. [Abstract] [Full Text] [PDF]

				T. F. McCutchan, D. Rathore, and J. Li Compensatory Evolution in the Human Malaria Parasite Plasmodium ovale Genetics, January 1, 2004; 166(1): 637 - 640. [Abstract] [Full Text] [PDF]

				Y. Chen and W. Stephan Compensatory evolution of a precursor messenger RNA secondary structure in the Drosophila melanogaster Adh gene PNAS, September 30, 2003; 100(20): 11499 - 11504. [Abstract] [Full Text] [PDF]

				H. Innan A two-locus gene conversion model with selection and its application to the human RHCE and RHD genes PNAS, July 22, 2003; 100(15): 8793 - 8798. [Abstract] [Full Text] [PDF]

				J. Duan, M. S. Wainwright, J. M. Comeron, N. Saitou, A. R. Sanders, J. Gelernter, and P. V. Gejman Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor Hum. Mol. Genet., February 1, 2003; 12(3): 205 - 216. [Abstract] [Full Text] [PDF]

				T. Itoh, W. Martin, and M. Nei Acceleration of genomic evolution caused by enhanced mutation rate in endocellular symbionts PNAS, October 1, 2002; 99(20): 12944 - 12948. [Abstract] [Full Text] [PDF]

				J. F. Baines, Y. Chen, A. Das, and W. Stephan DNA Sequence Variation at a Duplicated Gene: Excess of Replacement Polymorphism and Extensive Haplotype Structure in the Drosophila melanogasterbicoid Region Mol. Biol. Evol., July 1, 2002; 19(7): 989 - 998. [Abstract] [Full Text] [PDF]