Journal Article

DNA Slippage Occurs at Microsatellite Loci without Minimal Threshold Length in Humans: A Comparative Genomic Approach

Sébastien Leclercq, Eric Rivals and Philippe Jarne

in Genome Biology and Evolution

Published on behalf of Society for Molecular Biology and Evolution

Volume 2, issue , pages 325-335
Published in print January 2010 |
Published online May 2010 | e-ISSN: 1759-6653 | DOI: http://dx.doi.org/10.1093/gbe/evq023

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The dynamics of microsatellite, or short tandem repeats (STRs), is well documented for long, polymorphic loci, but much less is known for shorter ones. For example, the issue of a minimum threshold length for DNA slippage remains contentious. Model-fitting methods have generally concluded that slippage only occurs over a threshold length of about eight nucleotides, in contradiction with some direct observations of tandem duplications at shorter repeated sites. Using a comparative analysis of the human and chimpanzee genomes, we examined the mutation patterns at microsatellite loci with lengths as short as one period plus one nucleotide. We found that the rates of tandem insertions and deletions at microsatellite loci strongly deviated from background rates in other parts of the human genome and followed an exponential increase with STR size. More importantly, we detected no lower threshold length for slippage. The rate of tandem duplications at unrepeated sites was higher than expected from random insertions, providing evidence for genome-wide action of indel slippage (an alternative mechanism generating tandem repeats). The rate of point mutations adjacent to STRs did not differ from that estimated elsewhere in the genome, except around dinucleotide loci. Our results suggest that the emergence of STR depends on DNA slippage, indel slippage, and point mutations. We also found that the dynamics of tandem insertions and deletions differed in both rates and size at which these mutations take place. We discuss these results in both evolutionary and mechanistic terms.

Keywords: tandem repeats; comparative genomics; microsatellite emergence; DNA slippage; indel slippage; point mutations; human

Journal Article.  7494 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology ; Evolutionary Biology ; Genetics and Genomics

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