Homologous Recombination - Evolutionary Origins

Evolutionary Origins

Based on the similarity of their amino acid sequences, sets of proteins involved in homologous recombination are thought to share common evolutionary origins. One such set of proteins is the RecA/Rad51 protein family, which includes the RecA protein from bacteria, the Rad51 and Dmc1 proteins from eukaryotes and the RadA and RadB proteins from archaea. These proteins play key roles in the beginning stages of homologous recombination in the organisms that express them. The proteins in the RecA/Rad51 protein family share a long conserved region known as the RecA/Rad51 domain. Within this protein domain are two sequence motifs, Walker A motif and Walker B motif. The Walker A and B motifs allow members of the RecA/Rad51 protein family to engage in ATP hydrolysis, which provides energy for the proteins to drive reactions in homologous recombination.

Studies modeling the evolutionary relationships between the Rad51, Dmc1 and RadA proteins indicate that they are monophyletic, or that they share a common molecular ancestor. Within this protein family, Rad51 and Dmc1 are grouped together in a separate clade from RadA. One of the reasons for grouping these three proteins together is that they all possess a modified helix-turn-helix motif, which helps the proteins bind to DNA, toward their N-terminal ends. An ancient gene duplication event of a eukaryotic RecA gene and subsequent mutation has been proposed as a likely origin of the modern RAD51 and DMC1 genes.

The discovery of Dmc1 in several species of Giardia, one of the earliest protists to diverge as a eukaryote, suggests that meiotic homologous recombination—and thus meiosis itself—emerged very early in eukaryotic evolution. In addition to research on Dmc1, studies on the Spo11 protein have provided information on the origins of meiotic recombination. Spo11 is a type II topoisomerase that initiates homologous recombination in meiosis by making targeted double-strand breaks in DNA. Phylogenetic trees based on the sequence of genes similar to SPO11 in animals, fungi, plants, protists and archaea have led scientists to believe that the version Spo11 currently in eukaryotes emerged in the last common ancestor of eukaryotes and archaea.