Welcome to evolutionary developmental biology
(Evo Devo)
发育与进化
王 文
中德马普进化基因组学青年科学家小组
遗传资源与进化国家重点实验室
中国科学院昆明动物研究所
内容：
1、进化发育生物学简介
2、我们的思考和研究
做科学要有好的科学问题：
科学体系发展中不可回避、必须回答的问题
可以操作的问题
The Art of feasible!
背景：
• 遗传、发育和进化是生命科学中的本质问题，我们看到的各种各样的
生物组织、器官和性状无不是千百万年来遗传变异经自然选择固定并
最后通过发育展现而来。长期以来科学家们一直在试图把这三方面联
系起来。随着分子生物学、进化基因组学和发育生物学等现代生命科
学和技术的迅速发展和结合，这种努力首次变得富有希望。20多年前
兴起的进化发育生物学（Evolutionary developmental biology，常
简称Evo-Devo）是这种希望的一个开端，该学科试图从基因表达在发
育过程中的变化理解不同物种形态发生和功能的进化(Hall，1992）。
Haeckel‘s theory:
Ontogeny recapitulates phylogeny （1874）
• the fetal development of an individual (ontogeny) is a speeded-up replay
of millions of years of species evolution (phylogeny)
Thomas Hunt Morgan, “Embryology and Genetics” (1934)
第一次提出了胚胎发育的可能细胞分化机制：基因表达的时空分
化
在过去的30年中，我们已经发现了各种动物均使用的发育调控基
因基本的细胞过程，形成了“进化发育生物学”这一分支学科。
进化发育生物学（evolutionary developmental biology）：
旨在阐明生物进化中发育过程和机制怎样改变以及这些改变如何造就过去
和现在的生物多样性的一门学科。（Baguna and Garcia-Fernandez, 2003).
物种之间发育基因的比较（Sean Carrol， 2005）
常简称“Evo Devo”
Evo Devo
• Evolutionary development is so new
there isn’t even consensus as to
how to spell it.
• We spell it “evo devo”
because that’s how Sean
Carroll spells it.
• Others spell it “evo-devo”
and “evodevo.”
"Evo-devo" is one of the newest areas of biology. It seeks to explain evolutionary
events through the mechanisms of developmental biology. Its major questions are
often the questions of the late 1800s which had been left waiting for other
generations of biologists to unravel. We are those generations. These questions
include: How did wings evolve? How did limbs evolve? How did vertebrates arise
from invertebrates? How did vertebrates form their head?
The Modern Synthesis of the 1930s and 1940s was the synthesis of evolutionary
biology and population genetics. It is one of the greatest explanatory systems in
science, and it explains incredibly well the origin, maintenance, and evolution of
variations within populations of species. However, it did not identify the genes
involved in these changes, nor did it explain the origin of higher taxa. Evolutionary
developmental biology seeks to “complete” the synthesis by adding developmental
genetics to population genetics. Traditional Evo-devo looks at the regulatory regions
of genes rather than their coding sequences. It emphasizes the arrival of the fittest
rather than the survival of the fittest.
No crossing over
Subject to relentless selective sweep and background selection
in populations
Drosophila
Chromosome
Polymorphism of gene toy and sphinx in a worldwide and a local Drosophila
melanogaster population
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Stocks
Locations
toy intron1(847bp)
locus sphinx (4257bp)
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1 1 1111111111111 1 1 1 1 1 1 2 2 2 2 2 2 2 3 33 3 3 3 4
Position
1 1 1 1 1 2 3 4 4 5 5 7
1 1 11111111122 2 2 5 5 5 555555555555556666 6 8 9 1 2 7777777777777 7 7 7 8 9 9 0 1 2 2 2 5 7 0 11 1 8 9 0
1 4 8 8 9 0 4 4 6 1 3 5
9 1 3 99999999900 1 7 1 1 2 888899999999990000 5 1 2 3 9 2223333333334 5 8 9 8 1 3 3 4 2 4 4 4 0 0 33 7 0 1 0
3 1 0 1 3 4 2 2 2 0 7 8
0 6 0 12345678901 0 6 5 8 2 678901234567890123 4 5 0 8 9 7890124567890 5 1 9 7 9 7 4 7 6 1 5 0 6 8 67 1 7 5 4
closs19
closs20
253.4
253.27
Y2
Y10
Yep25
south1.10
southA.9
northN34
prunay
Rio
ok17
Hg84
LA79
ZH56
ZW30
ZW56
closs16
north7.13
253.38
253.35
253.30
USA
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Taiwan
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Israel
Israel
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Zimbabwe
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Zimbabwe
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World
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
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ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
ATTTTACAAAA
----------ATTTTACAAAA
population
A T T A A -----------------A T T A A -----------------A C T A A -----------------A C T A A -----------------A T T A A -----------------A T T A A -----------------A T T A A -----------------A C T A A -----------------A C T A A -----------------A C T A A -----------------A C T A A -----------------A T T A A -----------------A C T A A -----------------A C T A A -----------------A T C G T GGTGTATCATTTGCTTTC
A T C G T GGTGTATCATTTGCTTTC
A T C G T GGTGTATCATTTGCTTTC
A T C G T GGTGTATCATTTGCTTTC
A T C G T GGTGTATCATTTGCTTTC
A T C G T GGTGTATCATTTGCTTTC
A T C G T GGTGTATCATTTGCTTTC
T T C G T GGTGTATCATTTGCTTTC
A T C G T GGTGTATCATTTGCTTTC
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CCCACAATCCGCC
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CCCACAATCCGCC
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CCCACAATCCGCC
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CCCACAATCCGCC
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------ACACACA
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New York popalation (Upstate of New York, USA)
closs3
USA
A A A C C T G C T A C C
T C T ATTTTACAAAA A T T A A ------------------ G G T T C CCCACAATCCGCC C A - A T G C T A A G C A G AT C C T A
closs4
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closs7
USA
A A A C C T G C T A C C
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closs19
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A A A C C T G C T A C C
T C T ATTTTACAAAA A T T A A ------------------ G G T T C CCCACAATCCGCC C A - A T G C T A A G C A G AT C C T A
closs20
USA
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T C T ATTTTACAAAA A T T A A ------------------ G G T T C CCCACAATCCGCC C A - A T G C T A A G C A G AT C C T A
closs27
USA
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T C T ATTTTACAAAA A C T A A ------------------ G G T T C CCCACAATCCGCC C A - A T G C T A A G C A G AT C C T A
closs28
USA
A A A C C T G C T A C C
T C T ATTTTACAAAA A T T A A ------------------ G G T T C CCCACAATCCGCC C A - A T G C T A A G C A G AT C C T A
closs29
USA
A A A C C T G C T A C C
T C T ATTTTACAAAA A T T A A ------------------ G G T T C CCCACAATCCGCC C A - A T G C T A A G C A G AT C C T A
closs10
USA
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closs16
USA
A T G T C C A C G G C T
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USA
A T G T C C A C G G C T
T C C ATTTTACAAAA A T C G T GGTGTATCATTTGCTTTC T G T T C ------ACACACA C A - T - T T T C A G A T C -- C A A T
______________________________________________ ______________________________________________________________________________________________________________
Wang, W., Thornton, K., Berry, A. and Long, M. 2002, Science, 295: 134-137.
Variations in 18 gene regions were investigated
Wang, W., Thornton, K., Berry, A. and Long, M. 2002, Science, 295: 134-137.
Evo-Devo 中的重要概念:
(1) Toolkit genes: master genes that govern the formation and patterning of their
Bodies and body parts of all kinds of animals during development.
Despite being morphologically very diverse, multicellular organisms
are made by a very conserved set of regulatory genes (tool kit genes) playing
comparable developmental roles. This most unexpected finding
represented a powerful molecular proof of evolution as ‘descent
with modification’ (Darwin, 1859). Nonetheless, it brings a big
paradox: if developmental genes are the same, how are differences
in development and in the final morphology in different
organisms to be accounted for?
The likely answer:
differences between close organisms are due to differences in
expression of regulator genes driven by upstream regulators or by
changes in the range of downstream target genes.
传统的发育进化生物学研究范式
Evo-devo
If one of the Hox genes doesn’t
work…
Reduced expression of Ubx
Antp mutant
Ubx 突变对昆虫和节肢动物足肢的影响
果蝇
蜈蚣
Despite featuring a simple structure with a single body axis and radial
symmetry, Cnidarians bear the main elements of the genetic toolkit
(Finnerty and Martindale, 1999; Hobmayer et al., 2000; Spring et
al., 2002; Scholz and Technau, 2003; Yanze et al., 2001; Hayward
et al., 2002; Kozmik et al., 2003; Seipp et al., 2001, Wikramanayake
et al., 2003). In other words, Hox/ParaHox gene clusters, several
anteroposterior (or AP) genes (Otx, emx,..), the main set of
endodermal and mesodermal genes (Brachyury, Fork Head, snail/
slug, twist, MyoD, Mef2, dpp/BMPs, Wnt/ß-catenin,…), Pax genes,
germ cell genes (vasa, nanos ), as well as several genes involved
in apoptotic processes, were already in place 600 million of years
ago.
Evidence of such an extensive toolkit in Cnidarians debunks the notion
that gene diversification was at the base of the so-called Cambrian
explosion, whatever this may mean today (see Conway-Morris, 2003).
Body
plan
Garcia-Fernandez, Nature Review Genetics, 2005
Figure 2
行单细胞和多细胞生活酵母，Ashbya gossypii
(江会峰等, unpublished)
普通单细胞酵母，如Saccharomyces cerevisiae
(2) Phylogeny (系统发育)
Evolutionary-based questions have to be framed into a meaningful
phylogenetic framework; otherwise, whether a particular
morphology is ancestral or derived, whether a new morphology is
due to gain or loss of a feature, or whether a morphology has
evolved once or many times can not be properly answered unless
phyletic relationships among the comparing clades is known.
(3) Homology vs. convergent, parallel and homoplasmy
Sorting out parallelism from homology in landmark issues such as the origin(s)
of segmentation,the origin(s) of the eye (Hodin, 2000) warrants
further studies of additional phyla, and a deep understanding of
plasticity and constraints in gene and developmental evolution.
When a structure which is homologous between
closely related organisms is built using different genes, it should be
considered convergent rather than homologous.
Homologous genes may be responsible for non-homologous
morphologies. Genes and pathways are utilized on many separate
occasions during development.
As examples, the Notch-signalling pathway is broadly used
during Drosophila and vertebrate development (Simpson, 1997;
Robey, 1997), and hedgehog, TGF-β and Wnt family members are
used over and over again during development. Evolution may well
have worked by “genetic tinkering” (Jacob, 1977) or “bricolage” of
gene networks (Duboule and Wilkins, 1998).
paralogues, orthologues
Paralogues:源自基因重复；共同祖先是基因。
Orthologues：源自祖先物种，共同祖先是物种。
variety of eye types
• closely related animals have closely related eye genes,
which would result in similar eyes.
• Vertebrates: camera-like eyes with a single lens.
• Flies, lobsters and other arthropods: compound eyes made
up of many eye units.
都是同源的pax-6相关pathway控制，但最终形态不一样
Macroevolution vs. microevolution
As Dobzhansky (1937) firstly pointed out, the main issue in the
macro vs. microevolution debate is whether mutations resulting in
real evolutionary novelties are of the same kind as those occurring
daily or whether we should expect special, rare mutations only
occurring on geological time scales.
The future task for macro-Evo-Devo will be to unravel: i) preexisting
developmental potential; in other words, what was before
the Cambrian, which means analyzing the developmental toolkit
component of the closest sister groups, relatives of eubilaterians,
the acoelomorph flatworms (Ruiz-Trillo et al., 1999; 2002); ii) the
extent and quality of bricolage of this basal bilaterian toolkit
compared to higher bilaterians; and iii) trying to link the known, and
those which remain to be discovered, fossil groups
Ongoing debates or unsolved questions in evolutionary developmental biology
Origin of Bilateria
Origin of Vertebrata
Origin of Birds
Origin of Limbs
Origin of Brain
Multicellularity??
In the late 60s, population and quantitative genetics showed a high deal of genetic
variation within populations. Evolutionary developmental biologists thought of this
intraspecific variation in regulatory developmental genes as mere “noise”. However,
new applications of population genetics and artificial selection techniques to test the
potential of variation in developmental features is switftly changing this
appreciation. Six generations of artificial selection on wing eyespot size in the
butterfly Bicyclus, led to dramatic shifts in the range of eyespot sizes (reviewed in
Beldade and Brakefield, 2002). Further, Gompel and Carroll (2003) and Sucena et
al., (2003) have identified minor genetic changes correlating with
microevolutionary features in closely related Drosophila species: the distribution of
tricomes, or the pigmentation of the abdomen.
To start with, it seems wiser to leave aside big hot problems such
as the basis of the “Cambrian explosion” (despite their tremendous
interest) and concentrate on intra-phyletic, and even better intraclass,
intra-order and inter-generic, comparisons. Among the best
examples of this approach one could mention the role of Ultrabithorax
in morphological differences between Drosophila species (Stern,
1998), the divergence of cis-regulatory sequences in the achaetescute
gene complex between Drosophila melanogaster and D.
simulans (Skaer and Simpson, 2000), the variability among the evenskipped
stripe 2 in Drosophila (Ludwig et al., 2000).
但Hoskstra和Coyne认为1、
仅仅yellow的调控区改变不
足以导致翅斑点的产生，
2、没有阐明物种特异的cis
导致的物种特异的翅斑
Hoskstra and Coyne，2007,
Evolution 61-5:995-1016
Loss of an Enhancer in Stickleback Fish Evolution
leads to dramatic morphological difference
但Hoskstra和Coyne认为1、仅仅排除pitx1编码区的突变就认定是cis改变证据不足
2、不能排除其他基因编码区的突变
Hoskstra and Coyne，2007, Evolution 61-5:995-1016
Butterfly Wing Pattern Evolution Is Associated with Changes in a
Notch/Distal-less Temporal Pattern
Current biology 2004, 13:1159-1166
·但传统的进化发育生物学更多是探讨动物中古老的、共有的发育机制，很多
看法和假说难以在物种分化的水平得到验证和阐释。
·近年来Sean Carroll（2005）等开始研究近缘种间形态变异的基因调控机制
，并得出了形态变异主要是基因调控方式改变的结论。
·但根据我们过去一些年来研究新基因及其新功能起源进化的结果看，上述两
个Evo-Devo的研究范式可能处在了两个极端:
一个考察太过古老的事件因而容易流于争辨；
一个过于强调小的变异(regulatory sequence )而忽略基因组中重要的
遗传改变的作用。
植物的发育与进化