Transposition of human immunoglobulin V kappa genes within the same chromosome and the mechanism of their amplification.

The variable, joining and constant gene segments of the human immunoglobulin kappa locus (V kappa, J kappa and C kappa) are located on the short arm of chromosome 2 at 2p11-2p12. Here we describe a cluster of 11 V kappa genes on the long arm of chromosome 2 at 2cen-q11. By pulsed-field gel electrophoresis, cosmid cloning and DNA sequencing the cluster was shown to consist of four amplified units (amplicons). The amplicons, each 110-160 kb in size, are organized within 650 kb as an array of inverted repeats with short stretches of non-amplified DNA in between. Cloning and sequencing of three different joints between amplified and non-amplified DNA revealed the existence of parts of Alu repeats at each of the analysed joints. It is suggested that during evolution a group of five V kappa genes was transposed from the short to the long arm of chromosome 2 by a pericentric inversion. Three of the five V kappa genes were then amplified in two subsequent steps to yield the structure found in the majority of the present day population. The possible relation of this structure to a pericentric inversion of chromosome 2 that is seen cytogenetically in a small fraction of today's population is discussed.

Evolution of a group of transposed human V kappa genes.

Eleven V kappa genes within a genomic region which has been transposed from the short to the long arm of chromosome 2 have been characterized by sequence analyses. Nine of the analysed genes exist within the genome in three highly homologous copies each. Sequence comparisons of the triplicated genes make it very likely that the three copies of a given gene were produced at different times during evolution. A chain of events which led to a stepwise amplification of precursor genes is discussed.