GERM LINE MAINTENANCE OF THE PSEUDOGENE DONOR POOL FOR SOMATIC IMMUNOGLOBULIN GENE CONVERSION IN CHICKENS

Somatic immunoglobulin diversity is generated in avian species by sequential gene conversion of variable (V) gene segments of the immunoglobulin heavy- and light-chain loci during B-cell development. The germ line pools of donor sequence information for somatic V-region gene conversion are found in families of V pseudogenes, located 5' of the single functional V gene of each locus. The sequence relationships among the pseudogenes (PSIV(L)) and functional V(L)1 gene of the chicken light-chain alleles in three inbred strains were compared to determine the extent of diversity within the germ line pseudogene cluster. Numerous differences were observed. For ''ample, compared with the previously reported CB allele and the G4 allele, the S3 allele contains two intact pseudogenes between PSIV(L)16 and PSIV(L)18. These two adjacent PSIV(L) gene segments (PSIV(L)17a and PSIV(L)17b) could have given rise to the PSIV(L)17 segment of the G4 and CB alleles by homologous recombination. The majority of other sequence polymorphisms among the PSIV(L) alleles appear to be the result of meiotic gene conversion. The incidence of untemplated mutations within PSIV(L) segments is significantly lower than the incidence of mutation within the pseudogene flanking regions. Together with the observations that most PSIV(L) segments have open reading frames and lack stop codons, these data support the hypothesis that the PSIV(L) cluster resembles a functional multigene family maintained by evolutionary selection for its functional role in generating somatic antibody diversity. Meiotic gene conversion events within the PSIV(L) cluster serve both to introduce diversity by the exchange of short segments between family members and to prevent the accumulation of random mutations.