Growth hormone-releasing hormone (GRF) and pituitary adenylate cyclase-activating
polypeptide (PACAP) are members of the PACAP/Glucagon superfamily. The
family is proposed to have developed from an ancestral PACAP-like molecule in
invertebrates. Through successive exon, gene and genome duplications the family has
grown to include seven other members. In mammals GRF and PACAP are located on
different genes, but in fish, amphibians and birds they are located on the same gene. The
main function of GRF is the release of growth hormone (GH) from the pituitary. Also,
during development GRF influences the fetal pituitary and stimulates GH release during
late gestation. In contrast, the functions of PACAP are extremely varied. PACAP is the
newest member of the superfamily and there is still much work to be done before its
actions are well understood. Like GRF, PACAP is a releasing hormone acting on the
pituitary and in addition, the adrenal gland, pancreas and heart, as well as other organs.
Also, PACAP regulates smooth muscle in the vascular system, gut, respiratory tract and
reproductive tract During development PACAP affects proliferation, differentiation and
apoptosis.
GRF and PACAP are expressed throughout development in fish, beginning during
the blastula period in rainbow trout and at the end of gastrulation in zebrafish (earliest stage
examined). In rainbow trout the grf/pacap gene is expressed as two transcripts, a short and
a long transcript. The short transcript is produced by alternative splicing of the gene and
does not include the fourth exon which codes for GRF. The long transcript includes the coding regions for both GRF and PACAP. By this means PACAP can be regulated
separately from GRF. With the extensive role PACAP appears to play in development,
separate regulation of the hormone may be necessary. Expression of the grf/pacap gene in
zebrafish is widespread early in development and gradually becomes localized. Of particular interest is the expression of the grf/pacap transcript in regions associated with the
prechordal plate, an important organizing center in development. Although it is not yet
confirmed, there is evidence to suggest GRF and PACAP are expressed in the prechordal
plate and its derivatives in the gut and hatching gland. In addition, expression of the
grf/pacap transcript is observed in the neuroectoderm (eye, brain and spinal cord) and the
developing heart. Considering the expression pattern of GRF and PACAP, I propose that
one of both of these hormones may be involved in patterning during vertebrate
embryogenesis.
The evolution of gene families is thought to occur through successive exon, gene and genome duplications. Duplicate exons or genes become differentiated and eventually
gain new functions or become functionless. During evolution of the grf/pacap lineage,
several duplication events have occurred. Analysis of rainbow trout leads me to think that
this fish and other salmonids possess two copies of the grf/pacap gene. This is not
unexpected considering the tetraploid nature of salmonids. Present day mammals encode
GRF and PACAP on separate genes. At some point during the evolution of this lineage a
duplication event has occurred, possibly in early mammals or prior to the divergence of
birds. The study of multigene families is a useful way to understand evolutionary
processes. To this end I examined three members of multigene families from sockeye
salmon. Therefore, in addition to the evolutionary mechanisms and pathways that directed
grf/pacap gene evolution, I examined the ferritin-H subunit, the alpha-tubulin subunit and
the beta-globin subunit. These cDNA sequences are similar to their counterparts in other
teleost. The evolution of the ferritin gene family is particularly interesting because it
involves the addition or deletion of DNA sequences that affect regulation and cytosolic
location. / Graduate
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/9628 |
| Date | 06 July 2018 |
| Creators | Krueckl, Sandra Lea |
| Contributors | Sherwood, Nancy |
| Source Sets | University of Victoria |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
| Rights | Available to the World Wide Web |
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