CHICKEN IGL VARIABLE REGION GENE CONVERSIONS DISPLAY PSEUDOGENE DONOR PREFERENCE AND 5' TO 3' POLARITY

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 VL1 and VH1 genes with homologous sequences derived from V region pseudogene segments (ψV). 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 ψVL usage as gene conversion donors is shown to depend on the proximity of the ψVL segment to VL1, extent of homology with VL1, and relative orientation of the ψVL segments. Gene conversion events are not observed in the 5′ region of homology between ψVL segments and VL1, but are distributed throughout the remainder of the VL1, exon. The 5′ ends of individual gene conversion events always begin in regions of homology between the donor ψVL and recipient VL1 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.