发育与进化（ Evolutionary developmental biology ，常简称 Evo-DevoEvo-Devo））

王 文

中德 Max Planck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个体发育展现而来。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-DevoEvo-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" 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.

_____________________________________________________________________________________________________________________________________________________________Stocks Locations toy intron1(847bp) locus sphinx (4257bp)______________________________________________ ______________________________________________________________________________________________________________ 1 1 1111111111111 1 1 1 1 1 1 2 2 2 2 2 2 2 3 33 3 3 3 4Position 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

World populationcloss19 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 Acloss20 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 A253.4 Taiwan A A A C C T G C T A C T 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 A253.27 Taiwan A A A C C T G C T A G T T C T ATTTTACAAAA A C T A A ------------------ G G T T G CCCACAATCCGCC C A - A T G C T A A G C A G AT C C T AY2 Australia 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 AY10 Australia A A A C C T G C T A C T 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 AYep25 Australia A A A C T T G C T A C T 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 Asouth1.10 Israel A A A C C T G C T A G T 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 AsouthA.9 Israel A A A C C T G C T A G T 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 AnorthN34 Israel A A A C C T G A T A G T 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 Aprunay France A A A C C T G C T A C T 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 ARio Brazil A A A C C T G C T A C T 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 Aok17 Zimbabwe A A A C C T G C T A G T 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 AHg84 Zimbabwe A A A C C T G C T A G T T C T ATTTTACAAAA A C T A A ------------------ G G T T C CCCACAATCCGCC C G - A T G C T A A G C A G AT C C T ALA79 Zimbabwe A T G T C C A C T G C T T C T ATTTTACAAAA A T C G T GGTGTATCATTTGCTTTC G G C T C CCCACAATCCGCC C A - T - G C A C A A A A G AT T A T TZH56 Zimbabwe A T G T C C A C T G C T T C T ATTTTACAAAA A T C G T GGTGTATCATTTGCTTTC G G C T C CCCACAATCCGCC C A - T - G C T C A A A A G AT T A T TZW30 Zimbabwe A T G T C C A C T G C T T C T ATTTTACAAAA A T C G T GGTGTATCATTTGCTTTC G G C T C CCCACAATCCGCC C A - T - G C T C A A A A G AT T A T TZW56 Zimbabwe A T G T C C A C T G C T T C T ATTTTACAAAA A T C G T GGTGTATCATTTGCTTTC G G C T C CCCACAATCCGCC C A - T - G C T C A A A A G AT T A T Tcloss16 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 Tnorth7.13 Israel 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 C T C A G A T C -- C A A T253.38 Taiwan A T G T C C A C T G C T T C T ATTTTACAAAA A T C G T GGTGTATCATTTGCTTTC T C T C C ------ACACACA T A - T - T C T C T G A T C -- C A A T253.35 Taiwan A T G T C C A C G G C T A T T ----------- T T C G T GGTGTATCATTTGCTTTC T G T T C ------ACACACA C A T T - T C T C A G A T C -- C A A T253.30 Taiwan T T G T C C A C T G C T T C T ATTTTACAAAA A T C G T GGTGTATCATTTGCTTTC T C T T C ------ACACACA T A - T - T C T C A G A T C -- C A A T

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 Acloss4 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 Acloss7 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 Acloss19 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 Acloss20 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 Acloss27 USA A A A C C T G C T A G T 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 Acloss28 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 Acloss29 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 Acloss10 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 Tcloss16 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 Tcloss26 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______________________________________________ ______________________________________________________________________________________________________________

Polymorphism of gene toy and sphinx in a worldwide and a local Drosophilamelanogaster population

Wang, W., Thornton, K., Berry, A. and Long, M. 2002, Science, 295: 134-137.

群体遗传学案例（基因在群体中的变异情况）

No crossing overSubject to relentless selective sweep and background selectionin populations

DrosophilaChromosome

Variations in 18 gene regions were investigated

Wang, W., Thornton, K., Berry, A. and Long, M. 2002, Science, 295: 134-137.

(1) Phylogeny (系统发育 )

Evo-Devo 中的重要概念 :

Evo-Devo 中的重要概念 :

(2) Body plan

胚胎前后轴（ A － P ）、背腹轴（ D － V） 、左右轴（ L － R ）等决定

De Robertis, 2008)

Body plan

Evo-Devo 中的重要概念 :

(3) Toolkit genes: master genes that govern the formation and patterning of their Bodies and body parts of all kinds of animals.

Despite being morphologically very diverse, multicellular organismsare made by a very conserved set of regulatory genes (tool kit genes) playingcomparable developmental roles. This most unexpected findingrepresented a powerful molecular proof of evolution as ‘descentwith modification’ (Darwin, 1859).

最近：A set of genes that is required for development and is shared widely among species (Canestro et al, NRG, 2007)

传统的发育进化生物学研究范式：经典的进化发育生物学 (Evo Devo) 认为所有动物的发育由同一套工具箱基因 （ toolkit genes） 控制

果蝇

蜈蚣

在果蝇， ubx抑制腹部 dsl基因的表达的足产生，但在蜈蚣中其的 C端磷酸化位点不存在，导致不抑制腹部的足产生

不同动物眼睛的发育控制由一套同源的基因（ Pax6）控制

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?

(Canesttro et al., NRG, 2007)

(Canesttro et al., NRG, 2007)

最近， Sean Carroll等认为发育进化主要由调控序列的改变导致

Loss of an Enhancer in Stickleback Fish Evolution leads to dramatic morphological difference

Butterfly Wing Pattern Evolution Is Associated with Changes in a Notch/Distal-less Temporal Pattern

Current biology 2004, 13:1159-1166

(4) 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) warrantsfurther studies of additional phyla, and a deep understanding ofplasticity and constraints in gene and developmental evolution.When a structure which is homologous betweenclosely related organisms is built using different genes, it should beconsidered convergent rather than homologous.

Homologous genes may be responsible for non-homologousmorphologies. Genes and pathways are utilized on many separate occasions during development.As examples, the Notch-signalling pathway is broadly usedduring Drosophila and vertebrate development (Simpson, 1997;Robey, 1997), and hedgehog, TGF-β and Wnt family members areused over and over again during development. Evolution may wellhave worked by “genetic tinkering” (Jacob, 1977) or “bricolage” ofgene 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。

Macroevolution vs. microevolution

As Dobzhansky (1937) firstly pointed out, the main issue in themacro vs. microevolution debate is whether mutations resulting inreal evolutionary novelties are of the same kind as those occurringdaily or whether we should expect special, rare mutations onlyoccurring on geological time scales.

Evo Devo 使用的主要方法

1 、比较基因组学

2 、各种生物胚胎发育中基因的表达图式

3 、同源基因的替换或转基因

The future task for macro-Evo-Devo will be to unravel: i) preexistingdevelopmental potential; in other words, what was beforethe Cambrian, which means analyzing the developmental toolkitcomponent of the closest sister groups, relatives of eubilaterians,the acoelomorph flatworms (Ruiz-Trillo et al., 1999; 2002); ii) theextent and quality of bricolage of this basal bilaterian toolkitcompared to higher bilaterians; and iii) trying to link the known, andthose 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 LimbsOrigin of Brain

·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，上述两两个个 Evo-DevoEvo-Devo 的研究范式可能处在了两个极端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 )而忽略基因组中大的、重要的遗传改变的作用。

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.”

植物的发育与进化

2006 年

2006

2007 年

2007 年