Evolution of the gonadotropin-releasing hormone (GnRH) gene family in relation to vertebrate tetraploidizations.

The neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role in the control of reproductive functions. Vertebrates possess multiple GnRH isoforms that are classified into three main groups, namely GnRH1, GnRH2 and GnRH3. In the present study, we show that the chromosomal organization of the three GnRH loci is very well conserved among gnathostome species. We analyzed genes belonging to several other multigenic families that are present in the vicinity of GnRH genes. Five of them were seen to occur in four chromosomal regions that clearly form a paralogon. Moreover, we show that the homologous regions in the amphioxus genome are present on a single locus. Taken together, these observations indicate that GnRH1, GnRH2 and GnRH3 genes represent three paralogous genes that resulted from the two rounds of tetraploidization that took place early in vertebrate evolution. They confirm that the GnRH3 gene which is currently known only in teleost has most likely been lost in the tetrapod lineage. Finally, they suggest the existence of a fourth GnRH gene, named GnRH4. Whether the GnRH4 gene still exists in extant vertebrates is currently unknown. A search for this putative gene would be particularly useful in basal groups such as agnathans and cartilaginous fish.