Multiple transcripts encoding lamprey gonadotropin-releasing hormone-I precursors

The cDNA encoding lamprey prepro-gonadotropin releasing hormone-I (lamprey GnRH-I) has been isolated and sequenced in an agnathan, the sea lamprey, Pe tromyzon marinus. The lamprey GnRH-I precursor is the first identified in a n ancient lineage of vertebrates and has the same overall tripartite struct ure as other vertebrate GnRH precursors. The amino acid sequence of lamprey GnRH-I and the processing site (GIy-Lys-Arg) are highly conserved during 5 00 million years of evolution with 60-70% identity compared with those of t etrapod and teleost GnRH precursors. In contrast, the GnRH associated pepti de regions are markedly divergent, with less than 20% identity compared wit h all identified vertebrate precursors. Unlike all other known vertebrate G nRH precursors, which typically have one and in a single case two transcrip ts, three distinct transcripts were isolated and sequenced in lampreys. The se lamprey GnRH-I transcripts, termed GAP49, GAP50 and GAP58, differed in t he length of the GAP coding sequence and were demonstrated to be the produc ts of a single gene. Analysis of the lamprey GnRH-I gene intron-2 splice ju nction demonstrated that alternate splicing produces the different lamprey GnRH-I transcripts. Lamprey GnRH-I is the first GnRH gene demonstrated to u tilize splice sequence variants to produce multiple transcripts, which may reflect an ancestral gene regulatory mechanism.