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Paper in “Evolution and Development”
The Evolution of Signaling
Pathways In Animal Development
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André Pires-daSilva & Ralf J. Sommer
Nature Reviews Genetics, January 2003
Department of Evolutionary Biology, Max-Planck-Institute
für Entwicklungsbiologie, Germany
Background Knowledge
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The same set of seven pathways is
used many times in animal development
↓
Generate so much cellular and
morphological diversity
Essential Developmental Pathways
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Hh,
Hedgehog,
Wnt,
Wingless related,
TGF-, Transforming growth factor-
RTK,
Receptor tyrosine kinase
Notch,
JAK/STAT, Janus kinase/signal transducer
and activator of transcription
Nuclear hormone pathways
Questions
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How a few signalling pathways can generate
so much cellular and morphological diversity
during the evolution and the individual
development?
Properties of signaling pathways
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Signaling pathways are nonlinear, highly integrative
biological modules.
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Property 1: Flexibility → generation of evolutionary
novelty
Property 2: Robustness → ensure reproducible
outcomes of developmental processes
Signaling Flexibility: Mechanisms
1.
The same receptor can activate different intracellular
transducers in different tissues.
2.
Differences in the kinetics of the ligand or receptor might
generate distinct cellular outcomes.
3.
Combinatorial activation by signaling pathways might
result in the regulation of specific genes.
4.
cells that express distinct transcription factors might
respond differently when exposed to the same signals.
5.
Compartmentalization of the signal in the cell can
contribute to specificity.
Mechanisms of
signaling specificity
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a lethal-23 (LET-23) RTK signaling in
C. elegans
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b The strength of receptor affinity for
the Wnt ligand, results in the
activation of alternative pathways .
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c Drosophila even-skipped (eve)
gene contains functional binding sites
for response to Wnt, TGF- and RTK.
Mutation at any of these sites
abolishes eve expression.
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d In C. elegans, RTK stimulation
results in vulva induction only in the
hypodermis, owing to the tissuespecific expression of lineage-31.
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e GSK-3,its functional specificity
relies on compartmentalization in the
cell by cytosolic protein complexes
during Wnt signaling
Property 2 of signaling pathways :
Robustness
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Gene network models:
gene interactions for segmentation and neurogenetic
networks in Drosophila embryos
The interesting observation:
changes in many variables can result in the same
pattern of gene expression
↓
robustness
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Regulation mechanisms of robustness :
positive- and negative-feedback loops
Aspects of the evolution of
signaling pathways
1.
2.
3.
The genetic repertoire seen in
present-day species
The importance of the co-option of
signaling pathways for the generation
of morphological novelty.
The evolution of signaling pathways
Analysis of the evolution of
signaling pathways
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The pre-genome era.
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Important findings:
1. The signaling pathways evolved before the occurrence of
the bilaterians
2. The importance of gene duplication and subsequent
protein sequence divergence
Question
1. Evolution of signaling pathways →a prerequisite for the
occurrence of animal multicellularity?
“maybe”
2. Burst of gene duplications of signaling components→
Phylogenetic diversification of principal animal groups ? “no”
The phylogenetic placement of organisms has important
consequences on how the evolutionary pattern of
signalling pathways is interpreted.
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Gene duplication events do not correlate
with the origin of the principal animal groups
The post-genome era.
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The availability of whole-genome sequences of
different species
Questions
1. Are there any general trends between the
complexity of signaling pathways and body plans?
gene expansion ; whole-genome duplication
2. Do all pathways evolve in similar ways, such as by
an increase of paralogous proteins through gene
duplications?
The post-genome era.
The post-genome era.
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Two types of limitation restrict the findings solely
on the basis of in silico analysis:
1. The most important limitation in comparing
genomes and their proteins on a one-to-one level
stems from the modular nature of proteins, most of
which contain two or more domains.
2. A second limitation stems from the ability of
gene-prediction programs to detect divergent gene
sequences.
The in silico comparison of the evolution of
signalling pathways allows several important
conclusions
1.
The evolution of these signaling systems might
have been a prerequisite for the evolution of animal
multicellularity.
2.
Metazoan phyla differ in their number of signaling
genes.
3.
the availability of whole-genome sequences
provides a framework for the analysis of pathway
evolution.
Co-option of signaling pathways
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The process of re-using the existing
genetic units has been termed 'co-option‘
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Co-option was originally recognized as a
general principle for the evolution of
transcription factors
Co-option of the Hedgehog signaling pathway for
the induction of butterfly eyespots in the wing
Co-option of signaling pathways
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Conclusions:
1.
All developmental processes that are involved in
the generation of new structures require co-option
events.
the co-option of signaling pathways and
transcription factors is a common principle in
animal evolution.
2.
Case studies
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How do the pathways themselves evolve?
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Limitations of current case study:
It remains unclear how many more
components (often species and/or cell
specific) exist.
Searching for case studies
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Somatic sex determination in C. elegans.
The evolution of nematode sex determination
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Wilkins' hypothesis, the bottom-up evolution of C.
elegans sex determination, is testable by studying
other nematodes.
A study of more distantly related species, for which
genetic tools are available that are comparable with
those of C. elegans, can answer the question of how
complex signaling pathways might have evolved.
Questions to be answer
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Correlation: the number of signaling genes → the
diversification of body plans?
Types of signaling pathway hamper? morphological
evolution?
Is the flexibility of signaling systems sufficient to explain the
novelties of body plans?
How are new components integrated into existing networks,
and how does this change the behavior of a signaling network?
How do signaling systems really evolve at the micro
evolutionary level --- what type of mutations occur and how
are such changes fixed in natural populations?
Why do some pathways evolve faster than others?
Conclusions
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In all of these aspects, our understanding is
far from complete.
 general principles in evolutionary
developmental biology will emerge after a
sophisticated analysis of several case studies
has been carried out in selected animals.
 The light for answering the questions
completely:
whole-genome analysis
Critique
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Strength: directions of evolutionary
developmental biology→ post genomic study
The general tendency for the evolution of
signaling pathways is still unclear.
 How did the seven types of the pathways
related to each other during the evolution? Is
there a co-evolution?
 Slight errors in Figure 2.