Molecular evolution and origin of two peptide superfamilies
Date
2018-07-18
Authors
McRory, John E.
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Abstract
In mammals the glucagon and insulin superfamilies each
include a number of structurally-related hormones. The
origin of each superfamily has been the subject of debate for
many years resulting in an hypothesis that each superfamily
arose from a single ancestral gene encoding a bioactive
molecule. During evolution of the vertebrates, this gene is
thought to have duplicated and changed to encode the existing
family members.
The glucagon superfamily is composed of nine members
that have similar intron/exon structure, amino acid sequences
and gene length. Two neuropeptides in this family, growth
hormone-releasing hormone (GRF) and pituitary adenylate
cyclase-activating polypeptide (PACAP) are of special
interest in this thesis. In addition to GRF and PACAP, the
superfamily is composed of vasoactive intestinal peptide
(VIP), peptide histidine methionine (PHM), secretin, glucose-dependent
insulin-inducing peptide (GIP), glucagon, and
glucagon-like peptide (GLP)-I and -II, This thesis presents
nucleotide sequence data from a protochordate (tunicate;
Chelysoma productum), bony fish (catfish; Clarias
macrocephalus) and bird (chicken; Gallus domesticus) to help
in the interpretation of the evolutionary steps in the glucagon
superfamily.
Molecular biological techniques were used in isolating the
grf/pacap cDNA clones from tunicate, catfish and chicken and
the genes from tunicate and chicken. It was observed that
two family members, GRF and PACAP, are encoded by the same
gene in tunicate, catfish and chicken, unlike in mammals
where the two peptides are encoded by two separate genes.
Therefore, the duplication that gave rise to the two genes
must have occurred after the divergence of the
reptilian/avian lineage from the mammalian lineage about
250 million years ago. The tunicate, a sister group to
amphioxus and the vertebrates, but a taxon that evolved
before amphioxus, contains one distinct gene that encodes
[special characters omitted] and a second gene encoding [special characters omitted]. These four peptides are short compared to their
counterparts in mammals, but the biologically active core is
present. The two tunicate cDNA clones have high nucleotide
sequence identity (80%) suggesting a recent gene duplication.
In addition, a partial gene was isolated for each cDNA. The
gene organization shows that [special characters omitted] are each
on separate, but adjacent, exons in one gene; likewise
[special characters omitted] are on separate exons in the second
gene. The degree of identity among the four exons suggests
that two tunicate genes resulted from an exon duplication
followed by a complete gene duplication. These data suggest
that two ancestral tunicate genes are the progenitors from
which the existing vertebrate superfamily arose.
The evolution of another group of peptides in the insulin
superfamily was investigated also. The presence of a distinct
insulin and insulin-like growth factor (IGF) within the
protochordates (tunicates) was demonstrated using molecular
techniques. This is the first report of a true insulin and IGF
from an invertebrate. The amino acid sequence of insulin in
tunicates is 64% identical to the amino acid sequence in
human insulin, whereas tunicate IGF is 59% identical to both
human IGF-I and IGF-II. The tunicate clones encode amino
acids that have been shown in mammals to be essential for
receptor binding, for determination of tertiary structure and
for formation of disulfide linkages. Both mRNAs were found
to be expressed in the protochordate brain, neural gland, heart
and intestine by use of a reverse transcriptase/polymerase
chain reaction (RT/PCR). In situ analysis confirmed that the
insulin and igf mRNA synthesis occurs in neurons of the
tunicate brain. The widespread expression pattern and high
sequence identity between tunicate insulin and IGF (87%) may
reflect their common origin.
It is clear that protochordates are a nodal point in the
evaluation of two important peptide superfamilies. At least
six hormones (GRF, PACAP, VIP, glucagon, insulin and IGF)
identified in mammals come from a 600 million year lineage
in which the peptides have become more distinct from each
other in primary structure, length and tissue location.
Description
Keywords
Molecular evolution, Peptide hormones, Glucagon