Microsatellite Function

There are small sections of the DNA scattered throughout the genome that repeat. Termed microsatellites, these repeats vary in length but are rarely more than a few nucleotides long. Many evolutionists believe they have no function. However, given a created genome, that seems unlikely. Therefore we will take a brief look at microsatellites today to see whether there is evidence they have function.

Microsatellites are small repeated of DNA nucleotides that Graur(2016) believes are mostly nonfunctional, though he does admit the possibility that some might have a function.  However, recent evidence seems to point towards more microsatellites being functional than Graur recognized. Bagshaw (2017) presents a list of proposed functions for microsatellites in humans. He argues that microsatellites assist in gene expression,  influence the start and stop points of transcription, influence alternative splicing, and help maintain the proper structure of chromatin, among other, more speculative effects.

Humans are not the only organisms that have functional microsatellites.  Brown algae microsatellites were found to be involved in pathway responses, as well as stress response (Liu et al, 2016).  Hammack and Young (2004) associated a microsatellite with social behavior in voles.  At least some microsatellites seem to have a function of some kind.

There is another line of evidence that points to microsatellites having a function, though admittedly a weaker line of evidence.  Microsatellite instability (MSI) has been implicated in many diseases, such as cancer (Sawhney et al, 2006 and Kopitz et al, 2009). It does seem based on this paper (Geisler et al, 2003), and the one you cited (Cortes-Ciriano et al, 2017)that mismatch repair failing to work tends to generate MSI. Since we know MSI is associated with many diseases, mismatch repair failure is a significant issue. It seems reasonable that if mutations in microsatellites cause disease, the microsatellites must be doing something.  Further investigations of microsatellites for a potential function would probably be a good idea.   

There is a counterexample, however. I found a paper arguing that MSI actually helps regulate gene expression in some cases (Martin et al, 2005). However, the argument is flawed. The argument is that the mutations that cause MSI actually increase the virulence in the bacteria by changing gene expression. While this may be true, it does not prove instability in the microsatellites regulating gene expression is a good thing. It is situationally beneficial, in that it helps the bacterium evade the host defenses, but does not seem beneficial in the longterm. In fact, the microsatellite region that serves as a binding site for transcription factors is not expressed, except in iron-deficient conditions.

Something not mentioned above but a possibility worth considering is that microsatellites serve as scaffolding for the genome. In other words, the genome is structured in three dimensions. In three dimensions, something needs to hold the structure together. Microsatellites might serve as the glue and support structure to keep the genome together. Regardless of each microsatellites exact function, it is clear most of them have some kind of function, in some cases multiple functions.

References: 

Bagshaw A.T.M. 2017. Functional mechanisms of microsatellite DNA in eukaryotic genomes. Genome Biol Evol. 9(9):2428-2443.

Cortes-Ciriano I. Lee S. Park W. Y. Kim T. M. Park P. J. 2017. A molecular portrait of microsatellite instability across multiple cancers. Nat Commun. 8:15180. 

Graur, D. 2016. Molecular and genome evolution1st. Sunderland, (MA). Sinauer Associates, Inc. 564-565.

Geisler J.P. Goodheart M.J. Sood A.K. Holmes R.J. Hatterman-Zogg M.A. Buller R.E. 2003. Mismatch repair gene expression defects contribute to microsatellite instability in ovarian carcinoma.  Cancer. 98(10):2199-2206.

Hammock E.A.D. Young L.J. 2004. Functional microsatellite polymorphism associated with divergent social structure in vole species. Mol Biol Evol. 21(6):1057-1063.

Kopitz J. Patsos G. Andre S. Roeckel N. Gromes R. Gebert J. Gabius H.J. 2009. Compensation of loss of protein function in microsatellite-unstable colon cancer cells (HCT116): A gene-dependent effect on the cell surface glycan profile. Glycobiology. 19(7):726-734.

Liu F. Hu Z. Liu W. Li J. Wang W. Liang Z. Wang F. Sun X. 2016. Distribution, function and evolution characterization of microsatellite in Sargassum thunbergii (Fucales, Phaeophyta) transcriptome and their application in marker development. Sci Rep. 6:18947

Martin P. Makepeace K. Hill S.A. Hood D.W. Moxon E.R. 2005. Microsatellite instability regulates transcription factor binding and gene expression.  Proc Natl Acad Sci USA. 102(10):3800-3804. 

Sawhney M.S. Farrar W.D. Gudiseva S. Nelson D.B. Lederle F.A. Rector T.S. Bond J.H. 2006. Microsatellite instability in interval colon cancers. Gastroenterology. 131(6):P1700-P1705.

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