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postgraduate thesis: The relationship between the evolutionary origin of PACAP/GCG subfamily and two rounds of whole genome duplication in the beginning of vertebrate evolution
Title | The relationship between the evolutionary origin of PACAP/GCG subfamily and two rounds of whole genome duplication in the beginning of vertebrate evolution |
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Authors | |
Advisors | |
Issue Date | 2017 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | On, S. [安世桓]. (2017). The relationship between the evolutionary origin of PACAP/GCG subfamily and two rounds of whole genome duplication in the beginning of vertebrate evolution. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. |
Abstract | Peptides from pituitary adenylate cyclase‐activating polypeptide (PACAP) and glucagon
subfamilies were called “brain‐gut‐peptides” because of their pleiotropic actions both in
the CNS and the digestive system. It has long been proposed that these peptides with
similar amino acid sequence and physiological function share the same evolutionary origin
prior to the emergence of vertebrates and two rounds of whole genome duplication
(2WGD). However, identification of their orthologs in invertebrates had been hindered due
to the lack of significant sequence identity between putative members in invertebrates and
known peptides in vertebrates. Recently, successful identification of putative amphioxus
(Branchiostoma floridae, bf) parathyroid hormone‐like peptides and PACAP/glucagon‐like
peptides (PACAP/GLUCs) by Mirabeau and Joly allowed us to re‐investigate the
evolutionary origins of the two subfamilies in ancestral chordates using cephalochordates
as animal model. In this project, five amphioxus receptors phylogenetically belonging to
independent clade between PTH and PACAP/glucagon receptor subfamilies were
characterized. These cloned receptors showed synteny with most receptors from PTH and
PACAP/glucagon receptor subfamilies in three vertebrate species, spotted gar, Xenopus
and human, indicating that the genomic environment of these receptor subfamilies in
ancestral chordates were preserved by amphioxus. Functional analyses revealed that one
of the cloned receptors (bf98C) can be activated by endogenous parathyroid hormone‐like
peptides, whereas another receptor (bf95) only interacted with PACAP/GLUCs,
demonstrating the existence of PTHs‐receptor as well as PACAP/GLUCs‐receptor pairings
prior to the origin of vertebrates. Therefore, PACAP and glucagon receptor subfamilies as
well as their ligands likely evolved from a pairing system homologous to bf95‐PACAP/GLUCs
in ancestral chordates through 2WGD. Further studies on the physiology of the most
potent agonist, PACAP/GLUCa, among PACAP/GLUCs showed that the PACAP/GLUCsreceptor
system possessed many characteristics of its vertebrate orthologs/paralogs. By
qRT‐PCR and immunofluorescence staining it was found that PACAP/GLUCa also followed
the “brain‐gut” pattern with abundant expression of the peptides and its transcript in the
nucleus of Rohde in the nerve cord, homolog of neurosecretory cells of the hypothalamus,
Hatschek’s pit (Hp), homolog of vertebrate adenohypophysis, and the digestive tract.
Moreover, we have shown that after 72hrs’ exposure to high salinity (35‰) expression of
gh‐l and pacap/gluca transcripts in the head of amphioxi increased. This indicates that as
growth hormone‐like protein (GH‐L), which is mainly expressed in Hp of amphioxus, like
vertebrates, is involved in high salt tolerance. Furthermore, treatment of PACAP/GLUCa
after 72hrs acclimation to high salinity external environment promoted gh‐l transcript level
in amphioxi’s head. The involvement of PACAP/GLUCa in upregulation of GH‐L in the pit
mimics the regulation of GH by growth hormone releasing hormones in vertebrates,
suggesting the homolog between the operation of Hp and that of the vertebrate
adenohypophysis. Since feeding and growth control were proposed to be the promising
function of this external organ, Hp, the presence of PACAP/GLUCa in this primitive
adenohypophysis likely served as a foundation for developing the complicated control of
feeding behavior and growth by peptides from PACAP and GCG subfamilies in the
hypothalamus during the evolution of vertebrates. |
Degree | Doctor of Philosophy |
Subject | Polypeptides Chordata - Evolution |
Dept/Program | Biological Sciences |
Persistent Identifier | http://hdl.handle.net/10722/255404 |
DC Field | Value | Language |
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dc.contributor.advisor | Chow, BKC | - |
dc.contributor.advisor | Lee, TO | - |
dc.contributor.author | On, Sai-wun | - |
dc.contributor.author | 安世桓 | - |
dc.date.accessioned | 2018-07-05T07:43:25Z | - |
dc.date.available | 2018-07-05T07:43:25Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | On, S. [安世桓]. (2017). The relationship between the evolutionary origin of PACAP/GCG subfamily and two rounds of whole genome duplication in the beginning of vertebrate evolution. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. | - |
dc.identifier.uri | http://hdl.handle.net/10722/255404 | - |
dc.description.abstract | Peptides from pituitary adenylate cyclase‐activating polypeptide (PACAP) and glucagon subfamilies were called “brain‐gut‐peptides” because of their pleiotropic actions both in the CNS and the digestive system. It has long been proposed that these peptides with similar amino acid sequence and physiological function share the same evolutionary origin prior to the emergence of vertebrates and two rounds of whole genome duplication (2WGD). However, identification of their orthologs in invertebrates had been hindered due to the lack of significant sequence identity between putative members in invertebrates and known peptides in vertebrates. Recently, successful identification of putative amphioxus (Branchiostoma floridae, bf) parathyroid hormone‐like peptides and PACAP/glucagon‐like peptides (PACAP/GLUCs) by Mirabeau and Joly allowed us to re‐investigate the evolutionary origins of the two subfamilies in ancestral chordates using cephalochordates as animal model. In this project, five amphioxus receptors phylogenetically belonging to independent clade between PTH and PACAP/glucagon receptor subfamilies were characterized. These cloned receptors showed synteny with most receptors from PTH and PACAP/glucagon receptor subfamilies in three vertebrate species, spotted gar, Xenopus and human, indicating that the genomic environment of these receptor subfamilies in ancestral chordates were preserved by amphioxus. Functional analyses revealed that one of the cloned receptors (bf98C) can be activated by endogenous parathyroid hormone‐like peptides, whereas another receptor (bf95) only interacted with PACAP/GLUCs, demonstrating the existence of PTHs‐receptor as well as PACAP/GLUCs‐receptor pairings prior to the origin of vertebrates. Therefore, PACAP and glucagon receptor subfamilies as well as their ligands likely evolved from a pairing system homologous to bf95‐PACAP/GLUCs in ancestral chordates through 2WGD. Further studies on the physiology of the most potent agonist, PACAP/GLUCa, among PACAP/GLUCs showed that the PACAP/GLUCsreceptor system possessed many characteristics of its vertebrate orthologs/paralogs. By qRT‐PCR and immunofluorescence staining it was found that PACAP/GLUCa also followed the “brain‐gut” pattern with abundant expression of the peptides and its transcript in the nucleus of Rohde in the nerve cord, homolog of neurosecretory cells of the hypothalamus, Hatschek’s pit (Hp), homolog of vertebrate adenohypophysis, and the digestive tract. Moreover, we have shown that after 72hrs’ exposure to high salinity (35‰) expression of gh‐l and pacap/gluca transcripts in the head of amphioxi increased. This indicates that as growth hormone‐like protein (GH‐L), which is mainly expressed in Hp of amphioxus, like vertebrates, is involved in high salt tolerance. Furthermore, treatment of PACAP/GLUCa after 72hrs acclimation to high salinity external environment promoted gh‐l transcript level in amphioxi’s head. The involvement of PACAP/GLUCa in upregulation of GH‐L in the pit mimics the regulation of GH by growth hormone releasing hormones in vertebrates, suggesting the homolog between the operation of Hp and that of the vertebrate adenohypophysis. Since feeding and growth control were proposed to be the promising function of this external organ, Hp, the presence of PACAP/GLUCa in this primitive adenohypophysis likely served as a foundation for developing the complicated control of feeding behavior and growth by peptides from PACAP and GCG subfamilies in the hypothalamus during the evolution of vertebrates. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject.lcsh | Polypeptides | - |
dc.subject.lcsh | Chordata - Evolution | - |
dc.title | The relationship between the evolutionary origin of PACAP/GCG subfamily and two rounds of whole genome duplication in the beginning of vertebrate evolution | - |
dc.type | PG_Thesis | - |
dc.description.thesisname | Doctor of Philosophy | - |
dc.description.thesislevel | Doctoral | - |
dc.description.thesisdiscipline | Biological Sciences | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.5353/th_991044019384703414 | - |
dc.date.hkucongregation | 2018 | - |
dc.identifier.mmsid | 991044019384703414 | - |