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Finding and extending ancient simple sequence repeat-derived regions in the human genome.

Jonathan A Shortt1, Robert P Ruggiero2, Corey Cox1

  • 11Colorado Center for Personalized Medicine, University of Colorado School of Medicine, Aurora, CO 80045 USA.

Mobile DNA
|February 26, 2020
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Summary

This study reveals that over 6.7% of the human genome may be derived from ancient simple sequence repeats (SSRs), more than double previous estimates. The novel SSR-cloud method enhances detection of these crucial genomic regions.

Keywords:
Genome evolutionGenome structureMicrosatellitesRepeatsSSRTandem repeats

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Area of Science:

  • Genomics
  • Bioinformatics
  • Molecular Evolution

Background:

  • Simple sequence repeats (SSRs) constitute 3% of the human genome, but many ancient SSR-derived regions remain unannotated.
  • SSRs evolve through complex expansion, contraction, and mutation cycles, complicating their identification.
  • Current methods may miss ancient SSR-derived sequences due to these evolutionary dynamics.

Purpose of the Study:

  • To develop and apply an empirical, kmer-based approach to identify previously unannotated genome regions derived from SSRs.
  • To re-evaluate the proportion of the human genome originating from SSRs.
  • To investigate the evolutionary contribution of decaying repeats to genome structure.

Main Methods:

  • Applied a kmer-based approach, termed 'P-clouds', to identify SSR-clouds (groups of similar kmers) near known SSR loci.
  • Utilized identified SSR-clouds to detect likely SSR-derived regions across the entire human genome.
  • Validated the sensitivity of SSR-clouds by identifying poly-A sequences near ancient Alu elements.

Main Results:

  • Identified SSR-derived sequences in 6.77% of the human genome, more than double previous estimates.
  • Discovered millions of newly identified ancient SSR-derived loci.
  • SSR-clouds accurately detected poly-A sequences adjacent to AluJ termini, with lengths consistent with their origins.

Conclusions:

  • The SSR-cloud approach significantly enhances the detection of SSR-derived regions in the human genome.
  • This method reveals a substantially larger contribution of SSRs to genome structure than previously understood.
  • The findings enable deeper analysis of how decaying repeats shape genome architecture and evolution.