Simple Sequence Repeats as Evolutionary Tuning Knobs
Repetitive DNA sequences enable genetic adjustment of hereditary traits and thereby facilitate adaptation in a changing environment. In this way, such sequences resemble the tuning knobs on a stringed instrument, which allow simple and reversible adjustment of string tension to find the best tone.
Conventional evolutionary theory holds that high mutation rates must be disadvantageous. Nevertheless, high mutation rates do characterize certain DNA sequences, notably the tandem-repeating sequences known as microsatellites and minisatellites. Such sequences look a lot like junk, since their information content appears to be low and their mutational instability would seem to make them poor candidates for any critical function. But these "simple sequence repeats" are functionally integrated into the genome, where their length (i.e., the number of repeats) can exert a mutationally-adjustable quantitative influence on practically any aspect of gene function.
Could the high mutation rates of these sequences result from natural selection favoring mutability? Computer simulations by David King (SIU Department of Anatomy and SIU Department of Zoology) have demonstrated that the mutational properties of microsatellite DNA could be exploited by an evolving population. In these simulations, gradually changing environmental conditions imposed selection pressure on populations in which genetically-determined mutation rates and mutation impact factors were free to vary. Results showed that mutation rate can indeed increase as an indirect consequence of selection. [Mutational Landscape, figure and abstract] When suitably constrained, frequent mutations enable a population to adapt efficiently (that is, with minimal genetic load).
Simple sequence repeats can function like adjustable tuning knobs, facilitating the process of evolutionary change. They may be common precisely because indirect selection has favored their intrinsic instability.
- Facilitating evolution ( 2006 poster, ppt format)
- Kashi, Y., 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]
- John W. Fondon III and Harold R. Garner (2004) Molecular origins of rapid and continuous morphological evolution. PNAS 101(52): 18058-18063.
[news release from Univ. Texas]
- Rodent Social Behavior Encoded in Junk DNA (2005 NIH press release, Larry Young lab)
- Hammock, EAD, and Young, LJ (2005) Microsatellite instability generates diversity in brain and sociobehavioral traits. Science 308: 1630–1634.
- Lynn Helena Caporale (2004) Genes don't play dice, New Scientist 181(2437): 42-45 (6 March 2004).
- Lynn Helena Caporale (2003) Foresight in Genome Evolution, American Scientist 91(3): 234-241.
- Lynn Helena Caporale (2002) Darwin in the Genome, McGraw-Hill.
- King, D.G. (2000) Indirect selection on the mutational landscape: An evolved role for the mutability of repetitive DNA? In: Evolution 2000, (ed. M.J. Wade), Indiana University Conferences, Bloomington, Indiana [PDF file].
- King, D.G., and M. Soller (1999) Variation and fidelity: 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. [Abstract]
- King, D.G. (1999) Modelling selection for adjustable genes based on simple sequence repeats. In: Molecular Strategies in Biological Evolution, Annals of the New York Academy of Science 870:396-399. [Abstract]
- E.R. Moxon and C. Wills (1999) DNA Microsatellites: Agents of Evolution, Scientific American 280(1): 94-99.
- Pennisi, E. (1998) How the Genome Readies Itself for Evolution, Science 281:1131-1134.
- King, D.G., M. Soller, and Y. Kashi (1997) Evolutionary Tuning Knobs, Endeavour 21(1):36-40. [PDF file]
- Kashi, Y., 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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