Insight from the lamprey genome: glimpsing early vertebrate development via neuroendocrine-associated genes and shared synteny of gonadotropin-releasing hormone (GnRH)

Abstract

Study of the ancient lineage of jawless vertebrates is key to understanding the origins of vertebrate biology. The establishment of the neuroendocrine system with the hypothalamic-pituitary axis at its crux is of particular interest. Key neuroendocrine hormones in this system include the pivotal gonadotropin-releasing hormones (GnRHs) responsible for controlling reproduction via the pituitary. Previous data incorporating several lines of evidence showed all known vertebrate GnRHs were grouped into four paralogous lineages: GnRH1, 2, 3 and 4; with proposed evolutionary paths. Using the currently available lamprey genome assembly, we searched genes of the neuroendocrine system and summarize here the details representing the state of the current lamprey genome assembly. Additionally, we have analyzed in greater detail the evolutionary history of the GnRHs based on the information of the genomic neighborhood of the paralogs in lamprey as compared to other gnathostomes. Significantly, the current evidence suggests that two genome duplication events (both 1R and 2R) that generated the different fish and tetrapod paralogs took place before the divergence of the ancestral agnathans and gnathostome lineages. Syntenic analysis supports this evidence in that the previously-classified type IV GnRHs in lamprey (lGnRH-I and -III) share a common ancestry with GnRH2 and 3, and thus are no longer considered type IV GnRHs. Given the single amino acid difference between lGnRH-II and GnRH2 we propose that a GnRH2-like gene existed before the lamprey/gnathostome split giving rise to lGnRH-II and GnRH2. Furthermore, paralogous type 3 genes (lGnRH-I/III and GnRH3) evolved divergent structure/function in lamprey and gnathostome lineages.

Keywords: 1R; 1st round WGD; 2R; 2nd round of WGD; 3R; Agnathans; Evolution; GnRHs; Gnathostomes; NPY; Orthologs; Paralogs; Phylogenetics; WGD; base pair; bp; gonadotropin-releasing hormones; kb; kilobase; lGnRH; lamprey GnRH; neuropeptide Y; teleost-specific 3rd round of WGD; whole genome duplication.

Fig. 1.

Proposed scenario of the evolution of the GnRH gene family in vertebrates. The relative placement of the whole genome duplication events is indicated by 1R, 2R, and 3R. Open rectangles with X’s indicate lost loci. In the interest of space, the evolution of vertebrates is significantly condensed with several taxa remaining unrepresented and time (left-to-right axis) not drawn to scale; it is similar to the paradigm used by Kim and colleagues (2011), but abridged. The cloud represents the ambiguity about the timing of the lamprey/gnathostome split relative to the last shared whole genome duplication and the degree of paralog resolution prior to the split. The altered lamprey branches are also placed differently relative the other taxa to accommodate the established names of the lineages. The question mark above the lost lamprey branch is to signal we don’t know at this time when GnRH1 was lost in that lineage. The deduced amino acids corresponding to the lamprey GnRH II and GnRH2 (zebrafish and chicken) decapeptides are shown above the representative blocks with the single amino acid difference in lamprey highlighted. Importantly, although we have drawn the scenario where lamprey GnRH-II is orthologous to GnRH2; a scenario wherein lamprey GnRH-II and gnathostome GnRH3 share common ancestry (post duplication) is also plausible. Modified from Smith et al. (2013).