Evolution of neuropeptide signaling.
Learning objectives
1. Knowledge of the vasopressin/oxytocin-type neuropeptide signaling system as an example of an evolutionarily ancient and
conserved neuropeptide signaling system.
2. Knowledge of the physiological roles of the vasopressin/oxytocin-type neuropeptide signaling system in the animal kingdom
and how this can be used to infer possible roles of this system in the common ancestor of the Bilateria.
3 Knowledge of how characterization of neuropeptide signaling systems in invertebrates can enable understanding of the
evolutionary history and relationships of neuropeptides
e.g. – with reference
i) GnRH and AKH as examples
ii) The NPS/NG peptide/CCAP family as an example.
Evolution of neuropeptide signaling: making sense of neuropeptide diversity
1. There are lots of different neuropeptides, which range in size from 3 residues to over 40 residues
2. Some mammalian neuropeptides can be easily grouped into families of related neuropeptides because they share high
levels of sequence similarity (e.g. vasopressin and oxytocin)
3. However, some mammalian neuropeptides (e.g. TRH) do not share any apparent sequence similarity with other
neuropeptides.
4. Many neuropeptides that have been identified in invertebrates do not share any apparent sequence similarity with
neuropeptides that have been identified in mammals and other vertebrates.
5. So how can we make any sense of all this neuropeptide diversity? The key to an understanding of the evolution of
neuropeptide signaling has come from discovery of the receptors that mediate the effects of neuropeptides in mammals,
other vertebrates and invertebrates.
6. A paper published in 2013 by Mirabeau & Joly provides a comprehensive analysis of neuropeptide evolution in bilaterians
– see following slides and
Evolution of neuropeptide signaling: making sense of neuropeptide diversity
• There are lots of different neuropeptides, which range in size from 3 residues to over 40 residues
• Some mammalian neuropeptides can be easily grouped into families of related neuropeptides because they
share high levels of sequence similarity (e.g. vasopressin and oxytocin)
• However, some mammalian neuropeptides (e.g. TRH) do not share any apparent sequence similarity with other
neuropeptides.
• Many neuropeptides that have been identified in invertebrates do not share any apparent sequence similarity
with neuropeptides that have been identified in mammals and other vertebrates.
• So how can we make any sense of all this neuropeptide diversity? The key to an understanding of the evolution
of neuropeptide signaling has come from discovery of the receptors that mediate the effects of neuropeptides
in mammals, other vertebrates and invertebrates.
• A paper published in 2013 by Mirabeau & Joly provides a comprehensive analysis of neuropeptide evolution in
bilaterians – see following slides and http://www.pnas.org/content/110/22/E2028.full
,• Phylogenetic analysis of bilaterian rhodopsin and secretin receptors. Maximum likelihood tree of bilaterian rhodopsin
β (A), γ-type (B), and secretin (C) receptors, according to the GRAFS classification established in ref. 3. The tree is
structured in well-supported subtrees containing both clusters of protostome (blue) and deuterostome (pink) groups
of sequences. At the root of blue-pink subtrees (shown as black or green solid circles), a prototypic receptor of each
subtype was already present in the urbilaterian. Black solid circles indicate well-supported bilaterian GPCR families,
and green solid circles show hypothetical evolutionary relationships among bilaterian families. The bilaterian (b-),
protostomian (p-), deuterostomian (d-), chordate (c-), lophotrochozoan (-l), or arthropod (a-) origin is indicated by an
initial letter before each peptide GPCR acronym. Ancestral bilaterian clusters containing receptors characterized only
in either protostomes or deuterostomes (e.g., b-TRHR and b-ETHR) were colored with alternating blue and pink bands,
and bilaterian clusters containing no characterized receptors were shaded in gray. Photoreceptors and aminergic
receptors were used as an outgroup for rhodopsin β receptors (A), and human adhesion GPCRs were used as an
outgroup for the secretin receptors (C).
• Receptor phylogenetic tree and not just human receptors
• Grouped by colour
• The pink = deuterostome
• Purple= protostome
• All different interesting relationship are revealed
• Grouped the receptor based on whether they are protostome or deutestrome
• Showing that bringing together receptors systems (neuropeptide receptor system) in protostomes and deutestrome
so as go around the wheel see different pairing of protestomian and deutestromian neuropeptide systems based on
their receptors being similar to each other. Moreover, in that way all different, ingesting relationships are revealed.
• One example of what emerges from this sort of analysis in clade 3, which is showing the relationship between
receptor in humans, GnRH (pivotal reproductive hormone) and a hormone in insect called AKH
- Both hormones were discovered in the 1970s independently
- GnRH was identified in 1971 based on its gonadotropic actions
- AKH was identified in 1976 based on its identity to trigger or mobilise the production or release of lipids when the
insect flies. When insects fly, they need an energy source, which comes from mobilisation of lipid stores that give
rise to source of energy to enable the muscles to work during flying. AKH is the hormone that triggers lipids
- If align the sequence, can see that are only 2 features that are identical, which are the 2 post-translation
modification, pyroglutamate N-terminal and C-terminal amide. Across the sequence there is no similarity in
residues
- With the identification of the receptors of these 2 hormones it became apparent that in fact the receptors are
related. The GnRH and AKH receptors are homologous proteins. They are ortholog of each other, which is the
correct terminology.
-
, Gonadotropin-releasing hormone and adipokinetic hormone signaling systems share a common evolutionary origin
• This is an example of how identifying receptors of neuropeptides is revealing relationships between peptides or
neurohormones that are not recognised in being related to each other.
Molecular evolution of peptidergic signaling systems in bilaterians
• The table shows some of the pairing that has been established
• Some pairing are predictable and some are less predictable and not expected. This work is still ongoing in research as
some of the boxes are unfilled, which means scientist still do not know some information.
• There is enough evidence to suggest that there are clear relationships between neuropeptide systems in deuterostomes
(humans) and protostomes (insects) that is creating some pattern in our understanding of the evolution of neuropeptides
systems
•
• Will be focussing on vasopressin/oxytocin – type signalling, which is an example where it was not difficult to see the
relationship in the hormone of protostome and deutestrome.
•
•
Learning objectives
1. Knowledge of the vasopressin/oxytocin-type neuropeptide signaling system as an example of an evolutionarily ancient and
conserved neuropeptide signaling system.
2. Knowledge of the physiological roles of the vasopressin/oxytocin-type neuropeptide signaling system in the animal kingdom
and how this can be used to infer possible roles of this system in the common ancestor of the Bilateria.
3 Knowledge of how characterization of neuropeptide signaling systems in invertebrates can enable understanding of the
evolutionary history and relationships of neuropeptides
e.g. – with reference
i) GnRH and AKH as examples
ii) The NPS/NG peptide/CCAP family as an example.
Evolution of neuropeptide signaling: making sense of neuropeptide diversity
1. There are lots of different neuropeptides, which range in size from 3 residues to over 40 residues
2. Some mammalian neuropeptides can be easily grouped into families of related neuropeptides because they share high
levels of sequence similarity (e.g. vasopressin and oxytocin)
3. However, some mammalian neuropeptides (e.g. TRH) do not share any apparent sequence similarity with other
neuropeptides.
4. Many neuropeptides that have been identified in invertebrates do not share any apparent sequence similarity with
neuropeptides that have been identified in mammals and other vertebrates.
5. So how can we make any sense of all this neuropeptide diversity? The key to an understanding of the evolution of
neuropeptide signaling has come from discovery of the receptors that mediate the effects of neuropeptides in mammals,
other vertebrates and invertebrates.
6. A paper published in 2013 by Mirabeau & Joly provides a comprehensive analysis of neuropeptide evolution in bilaterians
– see following slides and
Evolution of neuropeptide signaling: making sense of neuropeptide diversity
• There are lots of different neuropeptides, which range in size from 3 residues to over 40 residues
• Some mammalian neuropeptides can be easily grouped into families of related neuropeptides because they
share high levels of sequence similarity (e.g. vasopressin and oxytocin)
• However, some mammalian neuropeptides (e.g. TRH) do not share any apparent sequence similarity with other
neuropeptides.
• Many neuropeptides that have been identified in invertebrates do not share any apparent sequence similarity
with neuropeptides that have been identified in mammals and other vertebrates.
• So how can we make any sense of all this neuropeptide diversity? The key to an understanding of the evolution
of neuropeptide signaling has come from discovery of the receptors that mediate the effects of neuropeptides
in mammals, other vertebrates and invertebrates.
• A paper published in 2013 by Mirabeau & Joly provides a comprehensive analysis of neuropeptide evolution in
bilaterians – see following slides and http://www.pnas.org/content/110/22/E2028.full
,• Phylogenetic analysis of bilaterian rhodopsin and secretin receptors. Maximum likelihood tree of bilaterian rhodopsin
β (A), γ-type (B), and secretin (C) receptors, according to the GRAFS classification established in ref. 3. The tree is
structured in well-supported subtrees containing both clusters of protostome (blue) and deuterostome (pink) groups
of sequences. At the root of blue-pink subtrees (shown as black or green solid circles), a prototypic receptor of each
subtype was already present in the urbilaterian. Black solid circles indicate well-supported bilaterian GPCR families,
and green solid circles show hypothetical evolutionary relationships among bilaterian families. The bilaterian (b-),
protostomian (p-), deuterostomian (d-), chordate (c-), lophotrochozoan (-l), or arthropod (a-) origin is indicated by an
initial letter before each peptide GPCR acronym. Ancestral bilaterian clusters containing receptors characterized only
in either protostomes or deuterostomes (e.g., b-TRHR and b-ETHR) were colored with alternating blue and pink bands,
and bilaterian clusters containing no characterized receptors were shaded in gray. Photoreceptors and aminergic
receptors were used as an outgroup for rhodopsin β receptors (A), and human adhesion GPCRs were used as an
outgroup for the secretin receptors (C).
• Receptor phylogenetic tree and not just human receptors
• Grouped by colour
• The pink = deuterostome
• Purple= protostome
• All different interesting relationship are revealed
• Grouped the receptor based on whether they are protostome or deutestrome
• Showing that bringing together receptors systems (neuropeptide receptor system) in protostomes and deutestrome
so as go around the wheel see different pairing of protestomian and deutestromian neuropeptide systems based on
their receptors being similar to each other. Moreover, in that way all different, ingesting relationships are revealed.
• One example of what emerges from this sort of analysis in clade 3, which is showing the relationship between
receptor in humans, GnRH (pivotal reproductive hormone) and a hormone in insect called AKH
- Both hormones were discovered in the 1970s independently
- GnRH was identified in 1971 based on its gonadotropic actions
- AKH was identified in 1976 based on its identity to trigger or mobilise the production or release of lipids when the
insect flies. When insects fly, they need an energy source, which comes from mobilisation of lipid stores that give
rise to source of energy to enable the muscles to work during flying. AKH is the hormone that triggers lipids
- If align the sequence, can see that are only 2 features that are identical, which are the 2 post-translation
modification, pyroglutamate N-terminal and C-terminal amide. Across the sequence there is no similarity in
residues
- With the identification of the receptors of these 2 hormones it became apparent that in fact the receptors are
related. The GnRH and AKH receptors are homologous proteins. They are ortholog of each other, which is the
correct terminology.
-
, Gonadotropin-releasing hormone and adipokinetic hormone signaling systems share a common evolutionary origin
• This is an example of how identifying receptors of neuropeptides is revealing relationships between peptides or
neurohormones that are not recognised in being related to each other.
Molecular evolution of peptidergic signaling systems in bilaterians
• The table shows some of the pairing that has been established
• Some pairing are predictable and some are less predictable and not expected. This work is still ongoing in research as
some of the boxes are unfilled, which means scientist still do not know some information.
• There is enough evidence to suggest that there are clear relationships between neuropeptide systems in deuterostomes
(humans) and protostomes (insects) that is creating some pattern in our understanding of the evolution of neuropeptides
systems
•
• Will be focussing on vasopressin/oxytocin – type signalling, which is an example where it was not difficult to see the
relationship in the hormone of protostome and deutestrome.
•
•
