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. 2020 Sep 18;39(21):e105857. doi: 10.15252/embj.2020105857

Figure 1. RAG‐mediated transposition and model for the evolution of the RAG recombinase.

Figure 1

  1. Diagram of the 12RSS and 23RSS, which differ based on the length of a poorly conserved spacer between relatively well‐conserved heptamer and nonamer elements (consensus sequences shown in dark letters).
  2. V(D)J recombination and transposition involve steps of substrate DNA recognition, nicking, hairpin formation, and end processing and joining (recombination, yielding coding joint and signal joint) or target DNA capture and integration (transposition). Shown are schematic diagrams of RAG‐DNA complexes during the transposition reaction. RAG/HMGB1, blue oval; 12RSS with flanking coding DNA, red; 23RSS and flanking coding DNA, yellow; target DNA, green.
  3. Model for RAG evolution from a transposase to a recombinase (Carmona & Schatz, 2017). In this model, an ancestor Transib transposon which encoded a RAG1‐like (RAG1L) transposase acquired a RAG2‐like (RAG2L) gene to generate the ancestral RAG‐like transposon. In some invertebrates, it remained a transposon, while in jawed vertebrates, the transposon inserted into a gene exon to generate split antigen receptor genes and the RAG1L and RAG2L transposase genes evolved to become the RAG1/RAG2 recombinase genes.
  4. Sequence alignment of RAG1 and RAG1‐like proteins in the vicinity of RAG1 R848. R848 from jawed vertebrates is highlighted in yellow. Red letters in blue box, relatively well‐conserved residues; white letters on red background, highly conserved residues.