Gene Regulatory Networks and the Evolution of Animal Body Plans

Eric H. Davidson, Douglas H. Erwin
Science 2002, 295:1669 (2002)
National Academy of Sciences, April 5, 2005; 102
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• Development of the animal body plan
• Different rate in the evolution
• Developmental GRNs features and four
components
• How GRNs explain changes of the
evolution
• Summery
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• blueprint
• symmetry, # of body segments and #
of limbs
• tube-within-a-tube vs. sac-like
• triploblasty
http://users.tamuk.edu/kfjab02/Biology/Introzoology/b1313_ch16.htm
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triploblasty
Baer's laws for embryology:
Two rules from four
1. The general characters of
the group to which an
embryo belongs appear in
development earlier than
the special characters.
2. The less general structural
relations are formed after
the more general, and so on,
until the most specific
appear.
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Schematic representation of
sea urchin embryo development
P. Oliveri, E. H. Davidson, Curr. Opin. Genet. Dev. 14, 351(2004).
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4700 ma
Major diversification of life in the Cambrian
Explosion. Many fossils
Marinoan glaciations
Possible "snowball Earth" period.
Followed by Good fossils of multi-celled animals.
oxygen levels in the atmosphere increased
630~8
50 ma
http://en.wikipedia.org/wiki/Geologic_time_scale
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Body plans dev
Different combination of
TF, cis-regulatory module
Temporal , spacial
GRN
GRN structure is inherently hierarchical, because each
phase of development has beginnings, middle stages, and
progressively more fine-scale terminal processes.
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Regulatory genes cis-regulatory modules
linkages
cis-regulatory modules:
eg. enhancer, silencer , insulator
> 300bp
> 10 binding sites
> 4 transcription factors
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intercellular
component
transcription
repess
Known
sequence
P. Oliveri, E. H. Davidson, Curr. Opin. Genet. Dev. 14, 351(2004).
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Sea urchin VS. Starfish
Kingdom: Animalia
Phylum: Echinodermata
Class: Echinoidea
Kingdom: Animalia
Phylum: Echinodermata
Class: Asteroidea
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Kingdom
biological classification
From Wikipedia
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Q1: why So little change in phylumand
superphylum-level body plans
since the Early Cambrian? Like
Tetrapod, segmented.
Q2: why Great changes have
subsequently occurred within phyla
and classes?
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• Kernels - inflexible, upstream
• plug-ins – repeatedly coopted
• Switch - I/O devices
• gene batteries
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• consist of regulatory genes
• to specify the spatial domain
• given developmental functions
• particular form - recursive wiring
• Interference with expression->
destroy kernel function altogether
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switch
plug-in
plug-in
kernel
2
3
4
switch
Gene batteries
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• a gene regulatory feedback loop
• all except delta are regulatory
genes
• highly recursive
• phase
endoderm(yellow)
mesoderm(gray)
• surrounded by
other network
linkages that are
not conserved
EH Davidson and DH Erwin. Science 2002, 295:1669 (2002)
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• the linkages are also
highly recursive.
• eg. the nkx2.5, tbx,
mef2c, and gata4
genes all receive
inputs from multiple
other genes of the
kernel, as do the tin,
doc, mid, pnr, and
mef2c genes of the
Drosophila network.
EH Davidson and DH Erwin. Science 2002, 295:1669 (2002)
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• Anterior to posterior and midline to
lateral specification of the nervous
system
• Eye field specification
• Gut regionalization
• Development of immune systems
• Regionalization of the hindbrain and
specification of neural crest
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• Structurally conserved
• used within and among species
• not dedicated to formation of given body
parts, providing inputs into regulatory
apparatus
• eg. affecting a confined repertoire of
transcription factors, are used
repeatedly, often acting as dominant
spatial repressors in the absence of
ligand and as facilitators of spatially
confined expression in its presence.
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• Flexible
• Homologous processes in related animals
• Evolutionarily very labile
• Wnt
• Transforming
growth factor-
B
• Fibroblast
growth factor
• Hedgehog
• Notch
• Epidermal
growth factor
K. M. Cadigan, R. Nusse, Genes Dev. 11, 3286 (1997).
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• Only deployed at the end of this
process
• structural genes :protein-coding
genes
• the products of which execute cell
type–specific functions
• Differentiation gene batteries display
inherent evolutionary lability and
undergo continuous renovation
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Outputs terminate the network
at the periphery of developmental
GRNs
• Control the progressive formation of
spatial patterns of gene expression
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• may be regulating other network
subcircuits
• appear to be responsible for many
kinds of evolutionary change in
developmental process
Eg. Cell cycle control
hox gene ->direct repressive on
expression of wing-patterning genes
-> morphology
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Change in them is
prohibited
Once GRNs kernels
assembled since
Cambrian ,they
could not be
disassembled!
The most frequent
and least
constrained
EH Davidson and DH Erwin. Science 2002, 295:1669 (2002)
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• Micro evolutionary thinking->
Temporally homogeneous way
intersects with mechanisms of GRN
change
• Comparative molecular->
the evolutionary point of origin
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• GRNs of subsequent adaptational
change is forced to lower since
Cambrian.
• Early assembly of kernels, plug-in
and switch, AND piecemeal alteration
of gene batteries provide evolution.
• The conserved kernels of extant
developmental GRNs is the answers
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cis-regulatory DNAs
regulate
execute
The program for development
transcription factors
components of cell signaling
pathways
classes of GRN componen
• kernels
• plug-ins
• Switch
• gene batteries
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• M. Levine, E. H. Davidson, Proc. Natl. Acad. Sci.
U.S.A.102, 4936 (2005).
• P. Oliveri, E. H. Davidson, Curr. Opin. Genet. Dev. 14,
351(2004).
• http://strc.herts.ac.uk/bio/maria/Projects.htm
• W. J. R. Longabaugh, E. H. Davidson, H. Bolouri,
Dev.Biol. 283, 1 (2005).
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• Thank you!!
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