The cDNA encoding lamprey prepro-gonadotropin releasing hormone-I (lamprey GnRH-I) has been isolated and sequenced in an agnathan, the sea lamprey, Petromyzon marinus. The lamprey GnRH-I precursor is the first identified in an ancient lineage of vertebrates and has the same overall tripartite structure as other vertebrate GnRH precursors. The amino acid sequence of lamprey GnRH-I and the processing site (Gly-Lys-Arg) are highly conserved during 500 million years of evolution with 60-70% identity compared with those of tetrapod and teleost GnRH precursors. In contrast, the GnRH associated peptide regions are markedly divergent, with less than 20% identity compared with all identified vertebrate precursors. Unlike all other known vertebrate GnRH precursors, which typically have one and in a single case two transcripts, three distinct transcripts were isolated and sequenced in lampreys. These lamprey GnRH-I transcripts, termed GAP49, GAP50 and GAP58, differed in the length of the GAP coding sequence and were demonstrated to be the products of a single gene. Analysis of the lamprey GnRH-I gene intron-2 splice junction demonstrated that alternate splicing produces the different lamprey GnRH-I transcripts. Lamprey GnRH-I is the first GnRH gene demonstrated to utilize splice sequence variants to produce multiple transcripts, which may reflect an ancestral gene regulatory mechanism.

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