Evolution of variable lymphocyte receptor B antibody loci in jawless vertebrates.

Abstract

Three types of variable lymphocyte receptor (VLR) genes, <i>VLRA</i>, <i>VLRB</i>, and <i>VLRC,</i> encode antigen recognition receptors in the extant jawless vertebrates, lampreys and hagfish. The somatically diversified repertoires of these VLRs are generated by serial stepwise copying of leucine-rich repeat (LRR) sequences into an incomplete germline <i>VLR</i> gene. Lymphocytes that express VLRA or VLRC are T cell-like, while VLRB-expressing cells are B cell-like. Here, we analyze the composition of the <i>VLRB</i> locus in different jawless vertebrates to elucidate its configuration and evolutionary modification. The incomplete germline <i>VLRB</i> genes of two hagfish species contain short noncoding intervening sequences, whereas germline <i>VLRB</i> genes in six representative lamprey species have much longer intervening sequences that exhibit notable genomic variation. Genomic clusters of potential <i>LRR</i> cassette donors, fragments of which are copied to complete <i>VLRB</i> gene assembly, are identified in Japanese lamprey and sea lamprey. In the sea lamprey, 428 <i>LRR</i> cassettes are located in five clusters spread over a total of 1.7 Mbp of chromosomal DNA. Preferential usage of the different donor cassettes for <i>VLRB</i> assemblage is characterized in our analysis, which reveals evolutionary modifications of the lamprey <i>VLRB</i> genes, elucidates the organization of the complex <i>VLRB</i> locus, and provides a comprehensive catalog of donor <i>VLRB</i> cassettes in sea lamprey and Japanese lamprey.