Evolution of mutation rates: Phylogenomic analysis of the photolyase/cryptochrome family

José Ignacio Lucas-Lledó, Michael Lynch

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Photoreactivation, one of the first DNA repair pathways to evolve, is the direct reversal of premutagenic lesions caused by ultraviolet (UV) irradiation, catalyzed by photolyases in a light-dependent, single-enzyme reaction. It has been experimentally shown that photoreactivation prevents UV mutagenesis in a broad range of species. In the absence of photoreactivation, UV-induced photolesions are repaired by the more complex and much less efficient nucleotide excision repair pathway. Despite their obvious beneficial effects, several lineages, including placental mammals, lost photolyase genes during evolution. In this study, we ask why photolyase genes have been lost in those lineages and discuss the significance of these losses in the context of the evolution of the genomic mutation rates. We first perform an extensive phylogenomic analysis of the photolyase/cryptochrome family, to assess what species lack each kind of photolyase gene. Then, we estimate the ratio of nonsynonymous to synonymous substitution rates in several groups of photolyase genes, as a proxy of the strength of purifying natural selection, and we ask whether less evolutionarily constrained photolyase genes are more likely lost. We also review functional data and compare the efficiency of different kinds of photolyases. We find that eukaryotic photolyases are, on average, less evolutionarily constrained than eubacterial ones and that the strength of natural selection is correlated with the affinity of photolyases for their substrates. We propose that the loss of photolyase genes in eukaryotic species may be due to weak natural selection and may result in a deleterious increase of their genomic mutation rates. In contrast, the loss of photolyase genes in prokaryotes may not cause an increase in the mutation rate and be neutral in most cases.

Original languageEnglish (US)
Pages (from-to)1143-1153
Number of pages11
JournalMolecular biology and evolution
Issue number5
StatePublished - May 2009
Externally publishedYes


  • DNA repair
  • Mutation rate evolution
  • Mutator gene
  • Photolyase
  • Photoreactivation

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


Dive into the research topics of 'Evolution of mutation rates: Phylogenomic analysis of the photolyase/cryptochrome family'. Together they form a unique fingerprint.

Cite this