Evolution of GnIH structures and functions in chordates (#73)
In 2000, we discovered
a novel hypothalamic neuropeptide that actively inhibits gonadotropin release in quail
and termed it gonadotropin-inhibitory hormone (GnIH).1 GnIH peptides have
since been identified in most representative species of gnathostomes.2
They all share a C-terminal LPXRFamide (X = L or Q) motif.2 GnIH
can inhibit gonadotropin synthesis and release by decreasing the activity of
GnRH neurons as well as by directly inhibiting pituitary gonadotrope activity
in birds and mammals.2 To investigate the evolutionary origin of GnIH and
its ancestral function, we identified GnIH precursor gene encoding GnIHs from
the brain of sea lamprey, the most ancient lineage of vertebrates.3 Lamprey GnIHs possessed
a
C-terminal PQRFa motif.3 One of
lamprey GnIHs stimulated the expression of lamprey GnRH in the hypothalamus and
GTHβ mRNA expression in the pituitary.3 Thus, GnIH may have emerged
in agnathans as a stimulatory neuropeptide that later diverged to an inhibitory
neuropeptide during the course of evolution from basal vertebrate to
later-evolved vertebrates, such as birds and mammals. From a structural
point of view, pain modulatory neuropeptides, such as neuropeptide FF (NPFF)
and NPAF, share a C-terminal PQRFa motif. Because we identified GnIH and NPFF
genes from the brain of agnathans, the origin of GnIH and NPFF genes may date
back before the emergence of early vertebrates.3,4 Recently, we
identified a novel gene encoding RFamide peptides in the amphioxus. Molecular phylogenetic analysis and synteny
analysis indicated that this gene is closely related to the genes of GnIH and NPFF of vertebrates. The identified protochordate gene is considered to
be a common ancestral form of GnIH and NPFF genes, suggesting that the origin
of GnIH and NPFF may date back to the time of the emergence of early chordates.
GnIH gene and NPFF gene may have diverged by whole-genome duplication in the
course of vertebrate evolution.