Increased rate of human mutations where DNA and RNA polymerases collide

Trends Genet. 2009 Dec;25(12):523-7. doi: 10.1016/j.tig.2009.10.002. Epub 2009 Oct 23.

Abstract

Gene density and orientation of genes in eukaryotes seem to be correlated with the replication origin and the mutation rate is greater in late replicating regions; however, the reason for these patterns is unknown. Here, we investigate predicted replication origins in the human genome and find that levels of polymorphism as well as divergence from the chimpanzee genome are greater in genes transcribed on the lagging strand than those on the leading strand. This might be caused by interference between RNA and DNA polymerases, and avoidance of collisions between these enzymes might be an evolutionary force shaping gene orientation and density surrounding replication start sites. Physical constraints might have a larger influence on genome evolution than previously thought.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Evolution
  • DNA-Directed DNA Polymerase / metabolism*
  • DNA-Directed RNA Polymerases / metabolism*
  • Humans
  • Mutation*
  • Replication Origin*

Substances

  • DNA-Directed RNA Polymerases
  • DNA-Directed DNA Polymerase