Tandem Repeat Instability and Genome Evolution

Abstract

Evolvability is the potential for a biological system to produce variation that can be acted upon by natural selection. Processes that promote selectable variation can facilitate adaptation to dynamic environments. Microsatellite repeats – sequences composed of repeated sets of up to nine nucleotides – provide one source of adaptive variation. Repeats mutate by the addition or loss of their unit nucleotide sequence, up to 100 000 times more frequently than point mutations. In a number of species, including humans, repeat mutations can cause disease (including neurological and skeletal disorders) as well as exert subtle and quantitative consequences on gene function, morphology, behaviour and life history traits. Understanding the underlying properties of repeat mutation – including causes and mechanisms – is critical for understanding trait variation, adaptation and a growing list of human disorders.

Key Concepts:

  • Recent discoveries in molecular genetics are challenging current dogma that claims independence between selection and mutation.

  • Tandem repeats in the genome are highly mutable, sometimes at frequencies of up to 100 000 times more than point mutations.

  • Nearly all aspects of DNA processing, and even transcription and stress, contribute to repeat mutation, making repeats important markers for genomic instability.

  • Microsatellite repeats encode their own mutability, thereby enabling local manipulation of mutation rates.

  • Changes in the lengths of tandem repeats can subtly and quantitatively modulate gene function, traits and disease.

  • Many genomic regions, including tandem repeats, mutate during cellular stress, suggesting that the genome is far more dynamic and susceptible to environmental processes than previously recognised.

Keywords: evolvability; stress‐induced mutagenesis; genome instability; tandem repeats; microsatellites; triplet repeat disorders; Hsp90 chaperone; genome evolution; natural selection

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Further Reading

Caporale LH (2012) Overview of the creative genome: effects of genome structure and sequence on the generation of variation and evolution. Annals of the New York Academy of Sciences 1267(1): 1–10.

Fonville NC, Ward RM and Mittelman D (2011) Stress‐induced modulators of repeat instability and genome evolution. Journal of Molecular Microbiology and Biotechnology 21(1–2): 36–44.

Hannan AJ (2010) TRPing up the genome: tandem repeat polymorphisms as dynamic sources of genetic variability in health and disease. Discovery Medicine 10(53): 314–321.

Mittelman D (ed.) (2013) Stress‐induced Mutagenesis. New York: Springer.

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Matthew Ward, R, and Mittelman, David(Feb 2013) Tandem Repeat Instability and Genome Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024945]