Genetic diversification by somatic gene conversion

Abstract

Gene conversion is a type of homologous recombination that leads to transfer of genetic information among homologous DNA sequences. It can be categorized into two classes: homogenizing and diversifying gene conversions. The former class results in neutralization and homogenization of any sequence variation among repetitive DNA sequences, and thus is important for concerted evolution. On the other hand, the latter functions to increase genetic diversity at the recombination-recipient loci. Thus, these two types of gene conversion play opposite roles in genome dynamics. Diversifying gene conversion is observed in the immunoglobulin (Ig) loci of chicken, rabbit, and other animals, and directs the diversification of Ig variable segments and acquisition of functional Ig repertoires. This type of gene conversion is initiated by the biased occurrence of recombination initiation events (e.g., DNA single- or double-strand breaks) on the recipient DNA site followed by unidirectional homologous recombination from multiple template sequences. Transcription and DNA accessibility is also important in the regulation of biased recombination initiation. In this review, we will discuss the biological significance and possible mechanisms of diversifying gene conversion in somatic cells of eukaryotes.

Figure 1

Gene conversion by the Synthesis-Dependent Strand Annealing (SDSA) mechanism.

Figure 2

Organization of the chicken immunoglobulin light chain (IgL) locus. The germ line chicken IgL locus consists of a tandem array of pseudo V segments (ψV1–25), Vλ, an intervening sequence with joining signals (open triangles) and a transcription silencer, J and C elements. After V(D)J recombination, a unique functional VλJ segment is generated. The V region in this segment functions as a recipient of successive templated gene conversions from the upstream pseudo V segments, thereby the DNA sequence in the V region is diversified.

Figure 3

Regulation of genome alteration and integrity by gene conversion. The donor/recipient choice for gene conversion among homologous DNA sequences is determined by the localization of recombination-initiating DNA lesions, which are introduced under the influence of epigenetic marks such as histone acetylation, local chromatin structure, and transcriptional activity (shown as broken wavy lines). Gene conversion with a single template sequence neutralizes the divergence of the homologous DNA sequences. Adversely, the convergent gene conversion from multiple different DNA sequences results in diversification of the recipient locus.