Increased rate of human mutations where DNA and RNA polymerases collide - PubMed

Increased rate of human mutations where DNA and RNA polymerases collide

Frank Grønlund Jørgensen et al. Trends Genet. 2009 Dec.

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.

Similar articles

• The relationship between DNA replication and human genome organization.

  Necsulea A, Guillet C, Cadoret JC, Prioleau MN, Duret L. Necsulea A, et al. Mol Biol Evol. 2009 Apr;26(4):729-41. doi: 10.1093/molbev/msn303. Epub 2009 Jan 6. Mol Biol Evol. 2009. PMID: 19126867

• The control mechanism for lagging strand polymerase recycling during bacteriophage T4 DNA replication.

  Yang J, Nelson SW, Benkovic SJ. Yang J, et al. Mol Cell. 2006 Jan 20;21(2):153-64. doi: 10.1016/j.molcel.2005.11.029. Mol Cell. 2006. PMID: 16427006

• Essentiality, not expressiveness, drives gene-strand bias in bacteria.

  Rocha EP, Danchin A. Rocha EP, et al. Nat Genet. 2003 Aug;34(4):377-8. doi: 10.1038/ng1209. Nat Genet. 2003. PMID: 12847524

• DNA Polymerases Divide the Labor of Genome Replication.

  Lujan SA, Williams JS, Kunkel TA. Lujan SA, et al. Trends Cell Biol. 2016 Sep;26(9):640-654. doi: 10.1016/j.tcb.2016.04.012. Epub 2016 Jun 1. Trends Cell Biol. 2016. PMID: 27262731 Free PMC article. Review.

• [Structural and functional dynamics of DNA and RNA polymerases].

  Vlasov VA, Dymshits GM, Lavrik OI. Vlasov VA, et al. Mol Biol (Mosk). 1998 Jan-Feb;32(1):5-18. Mol Biol (Mosk). 1998. PMID: 9566247 Review. Russian. No abstract available.

Cited by

• Variation in heterozygosity predicts variation in human substitution rates between populations, individuals and genomic regions.

  Amos W. Amos W. PLoS One. 2013 Apr 30;8(4):e63048. doi: 10.1371/journal.pone.0063048. Print 2013. PLoS One. 2013. PMID: 23646173 Free PMC article.

• Evaluating genome-scale approaches to eukaryotic DNA replication.

  Gilbert DM. Gilbert DM. Nat Rev Genet. 2010 Oct;11(10):673-84. doi: 10.1038/nrg2830. Epub 2010 Sep 1. Nat Rev Genet. 2010. PMID: 20811343 Free PMC article. Review.

• Large-Scale Comparative Analysis of Codon Models Accounting for Protein and Nucleotide Selection.

  Davydov II, Salamin N, Robinson-Rechavi M. Davydov II, et al. Mol Biol Evol. 2019 Jun 1;36(6):1316-1332. doi: 10.1093/molbev/msz048. Mol Biol Evol. 2019. PMID: 30847475 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • ClinicalKey
  • Elsevier Science