Substitutions of short heterologous DNA segments of intragenomic or extragenomic origins produce clustered genomic polymorphisms

Proc Natl Acad Sci U S A. 2016 Dec 27;113(52):15066-15071. doi: 10.1073/pnas.1615819114. Epub 2016 Dec 12.


In a screen for unexplained mutation events we identified a previously unrecognized mechanism generating clustered DNA polymorphisms such as microindels and cumulative SNPs. The mechanism, short-patch double illegitimate recombination (SPDIR), facilitates short single-stranded DNA molecules to invade and replace genomic DNA through two joint illegitimate recombination events. SPDIR is controlled by key components of the cellular genome maintenance machinery in the gram-negative bacterium Acinetobacter baylyi. The source DNA is primarily intragenomic but can also be acquired through horizontal gene transfer. The DNA replacements are nonreciprocal and locus independent. Bioinformatic approaches reveal occurrence of SPDIR events in the gram-positive human pathogen Streptococcus pneumoniae and in the human genome.

Keywords: illegitimate recombination; microindels; mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter / genetics
  • Alleles
  • Computational Biology / methods
  • Cytoplasm / metabolism
  • DNA / genetics*
  • DNA Replication
  • DNA, Single-Stranded / genetics
  • Gene Deletion
  • Gene Transfer, Horizontal
  • Genome, Human
  • Genomics
  • Genotype
  • Humans
  • Mutagens
  • Mutation*
  • Plasmids / metabolism
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Recombination, Genetic
  • Sequence Analysis, DNA
  • Streptococcus pneumoniae / genetics*


  • DNA, Single-Stranded
  • Mutagens
  • DNA