Chicken IgL variable region gene conversions display pseudogene donor preference and 5' to 3' polarity.

Abstract

Chicken immunoglobulin variable region diversity is generated during B-cell development in the bursa of Fabricius by intrachromosomal gene conversion, resulting in the replacement of sequence blocks within the unique rearranged Vu and Vm genes with homologous sequences derived from V region pseudogene segments (lgV1. In this report, the nucleotide sequences of 217 gene conversion events in 52 random IgL clones were analyzed to characterize the molecular mechanism of gene conversion. The frequency of ~V, usage as gene conversion donors is shown to depend on the proximity of the ~gVr segment to Vr~, extent of homology with V~I, and relative orientation of the ~gVL segments. Gene conversion events are not observed in the 5' region of homology between yVL segments and Vu, but are distributed throughout the remainder of the V~ exon. The 5' ends of individual gene conversion events always begin in regions of homology between the donor ~gVL and recipient VL~ gene, whereas the 3' ends can occur in regions of nonhomology and often have nucleotide insertions or deletions. These results suggest a 5' to 3' polarity in the gene conversion mechanism. The implications of our data are discussed in relation to current molecular models of gene conversion.

Effect of Environmental Antigens on the Ig Diversification and the Selection of Productive V-J Joints in the Bursa

“…BDL chicken (Fig. 5, A and C), the preferential usage of pseudogenes located in the inverted orientation and more proximal to the rearranged V-J locus was generally confirmed as described previously for the random IgL clones (7,20). The local follicle preference of the pseudogene donor as V23 may be an accidental event in a total of ϳ10 4 follicles per bursa.…”

Gene conversion in human rearranged immunoglobulin genes

“…The mechanism of gene conversion in rearranged immunoglobulin genes is unknown but it can be deduced that there must be some means of overcoming the repression of recombination between diverged sequences in the presence of a normal MMR system, and that invasion may occur by a single 3' end only since the process appears to be uni-directional (McCormack and Thompson 1990). It is thus highly likely to involve heteroduplex formation and in this case the MMR system might not be able to distinguish between the original and copied strand, resulting in some corrections on one strand and some on the other (Martin and Scharff 2002), i.e., some towards the original sequence and some to the template sequence (Fig.…”

Evolution of Antigen Binding Receptors

“…The frequency of V L use depends on the proximity of the pseudogene and target genes as well as the extent of identity and their relative orientation. Homology in the 5 pseudogene and target is most essential and evidence for polarity in the gene conversion mechanism(s) has been presented (101). In addition to gene conversion, a number of mechanisms, including imprecise joining, somatic point mutation, single nonrandom nucleotide additions (102), and V gene replacement (99), further diversify light-chain genes.…”