1、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,Welcome to evolutionary developmental biology(Evo Devo),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
2、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）。,Haeckels theory:Ontogeny recapitulates phylogeny （1874）,the fetal development of an individual (ontogeny) is a speeded-up replay of mil
3、lions 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-Fern
4、andez, 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 isnt even consensus as to how to spell it. We spell it “evo devo” because thats how Sean Carroll spells it.Others spell it “evo-devo” and “evodevo.”,Evo-devo is one of the newest areas of biolo
5、gy. 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 evol
6、ve? 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 incred
7、ibly 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 g
8、enetics 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 overSubject to relentless selective sweep and background selectionin populat
9、ions,DrosophilaChromosome,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.,Variations in 18 gene regions were investigated,Wang, W., Thornton, K., Berry, A. and Long, M. 2002,
10、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 organismsare made by a very conserved set of regulatory
11、genes (tool kit genes) playingcomparable developmental roles. This most unexpected findingrepresented a powerful molecular proof of evolution as descentwith modification (Darwin, 1859). Nonetheless, it brings a bigparadox: if developmental genes are the same, how are differencesin development and in
12、 the final morphology in differentorganisms to be accounted for?The likely answer:differences between close organisms are due to differences inexpression of regulator genes driven by upstream regulators or bychanges 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 ge
13、nes doesnt 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 radialsymmetry, Cnidarians bear the main elements of the genetic toolkit(Finnerty and Martindale, 1999; Hobmayer et al., 2000; Spring etal., 2002; Scholz a
14、nd Technau, 2003; Yanze et al., 2001; Haywardet al., 2002; Kozmik et al., 2003; Seipp et al., 2001, Wikramanayakeet al., 2003). In other words, Hox/ParaHox gene clusters, severalanteroposterior (or AP) genes (Otx, emx,.), the main set ofendodermal and mesodermal genes (Brachyury, Fork Head, snail/sl
15、ug, twist, MyoD, Mef2, dpp/BMPs, Wnt/-catenin,), Pax genes,germ cell genes (vasa, nanos ), as well as several genes involvedin apoptotic processes, were already in place 600 million of yearsago.Evidence of such an extensive toolkit in Cnidarians debunks the notion that gene diversification was at th
16、e base of the so-called Cambrian explosion, whatever this may mean today (see Conway-Morris, 2003).,Body plan,Garcia-Fernandez, Nature Review Genetics, 2005,普通单细胞酵母，如Saccharomyces cerevisiae,行单细胞和多细胞生活酵母，Ashbya gossypii,(江会峰等, unpublished),(2) Phylogeny (系统发育),Evolutionary-based questions have to be
17、 framed into a meaningfulphylogenetic framework; otherwise, whether a particularmorphology is ancestral or derived, whether a new morphology isdue to gain or loss of a feature, or whether a morphology hasevolved once or many times can not be properly answered unlessphyletic relationships among the c
18、omparing clades is known.,(3) Homology vs. convergent, parallel and homoplasmySorting 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 c
19、onstraints 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 uti
20、lized 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- and Wnt family members areused over and over again during development. Evolution may wellhave work
21、ed by “genetic tinkering” (Jacob, 1977) or “bricolage” ofgene networks (Duboule and Wilkins, 1998).paralogues, orthologuesParalogues: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
22、: 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 themacro vs. microevolution debate is whether mutations r
23、esulting inreal evolutionary novelties are of the same kind as those occurringdaily or whether we should expect special, rare mutations onlyoccurring on geological time scales.,The future task for macro-Evo-Devo will be to unravel: i) preexistingdevelopmental potential; in other words, what was befo
24、rethe 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
25、) trying to link the known, andthose which remain to be discovered, fossil groups,Ongoing debates or unsolved questions in evolutionary developmental biologyOrigin of Bilateria Origin of Vertebrata Origin of Birds Origin of LimbsOrigin of BrainMulticellularity?,In the late 60s, population and quanti
26、tative genetics showed a high deal of genetic variation within populations. Evolutionary developmental biologists thought of thisintraspecific variation in regulatory developmental genes as mere “noise”. However, new applications of population genetics and artificial selection techniques to test the
27、 potential of variation in developmental features is switftly changing this appreciation. Six generations of artificial selection on wing eyespot size in thebutterfly Bicyclus, led to dramatic shifts in the range of eyespot sizes (reviewed in Beldade and Brakefield, 2002). Further, Gompel and Carrol
28、l (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 suchas the basis
29、of the “Cambrian explosion” (despite their tremendousinterest) and concentrate on intra-phyletic, and even better intraclass,intra-order and inter-generic, comparisons. Among the bestexamples of this approach one could mention the role of Ultrabithoraxin morphological differences between Drosophila
30、species (Stern,1998), the divergence of cis-regulatory sequences in the achaetescutegene complex between Drosophila melanogaster and D.simulans (Skaer and Simpson, 2000), the variability among the evenskippedstripe 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
31、、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
32、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,
