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The evolution of simple sequence repeats as functional elements in adjustable genes

In:  S.P. Wasser, ed., Evolutionary Theory and Processes: Modern Perspectives, pp. 65-82.  Kluwer Academic Publishers, Dordrecht, The Netherlands.

by David G. King
Department of Anatomy and Department of Zoology, Southern Illinois University Carbondale, Illinois

and Morris Soller
Department of Genetics, The Hebrew University, Jerusalem


The functional properties of simple sequence repeats (SSRs) support an expanded understanding of evolution's effect on mutability.  These DNA tracts are characterized by high rates of gain or loss in the number of tandem repetitions of a short DNA motif. Such mutations are remarkable for being frequent, site-specific and readily reversible.  Furthermore, many SSRs are functionally integrated into the genome, so that such changes in tract length can exert a quantitative regulatory effect on gene transcription activity.  Although the characteristic mutability of SSRs increases the site-specific rate of mutation, the quantitative effect minimizes the probability of significantly deleterious outcome.  Such mutable sites can thus create a favorable balance between the costs and the benefits of mutability.

SSR alleles which undergo changes in length can nevertheless retain their characteristic mutability.  Consequently, selection for favorable alleles will indirectly select the mutability function by which those alleles arose.  Conversely, SSR alleles can undergo site specific modification of their mutability, for example by mutation which alters the purity of motif repetition, while retaining their characteristic effect on phenotype and fitness.  Indirect selection can thereby shape the degree of mutability for any gene that includes a functional SSR.

Genes associated with SSRs may be favored by indirect selection whenever quantitative variation in the affected traits can provide a population with genetic resiliency for adaptation, especially in fluctuating or heterogeneous environments.  Such "adjustable genes" may provide a prolific and evolutionarily significant source of quantitative genetic variation.

Also see:

D.G. King and Y. Kashi (2007)  Mutation rate variation in eukaryotes: evolutionary implications of site-specific mechanisms.  Nature Reviews Genetics 8, (November 2007) | doi:10.1038/nrg2158-c1

D.G. King and Y. Kashi (2007)  Mutability and Evolvability:  Indirect selection for mutability.  Heredity 99:123-124. doi:10.1038/sj.hdy.6800998

Y. Kashi and D.G. King (2006)  Has simple sequence repeat mutability been selected to facilitate evolution?  Israel Journal of Ecology and Evolution 52:331-342.  doi:10.1560/IJEE_52_3-4_331

Y. Kashi and D.G. King (2006)  Simple Sequence Repeats as Advantageous Mutators in Evolution.  Trends in Genetics 22: 253-259.  [Abstract]

King, D.G., E.N. Trifonov, and Y. Kashi  (2006)  Tuning Knobs in the Genome:  Evolution of Simple Sequence Repeats by Indirect Selection.  In: Lynn H. Caporale, ed., The Implicit Genome, Oxford University Press.  [Abstract]   [Table of contents for The Implicit Genome]

King, D.G., M. Soller and Y. Kashi (1997)  Evolutionary tuning knobs.  Endeavour 21:36-40.  [related page]  [PDF text]

Y. Kashi, D.G. King, and M. Soller (1997)  Simple sequence repeats as a source of quantitative genetic variation.  Trends in Genetics 13:74-78.  [Abstract]  [PDF text]

King, D.G. (1994)  Triplet repeat DNA as a highly mutable regulatory mechanism.  Science 263:595-596.  [PDF text]

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Last updated:  7 January 2008 / dgk