发育与进化 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 （Evolutionary developmental biology，常简称Evo-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： The Art of feasible! 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-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)

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 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 "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.

melanogaster population 群体遗传学案例（基因在群体中的变异情况） Polymorphism of gene toy and sphinx in a worldwide and a local Drosophila melanogaster population Wang, W., Thornton, K., Berry, A. and Long, M. 2002, Science, 295: 134-137.

No crossing over Subject to relentless selective sweep and background selection in populations Drosophila Chromosome

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) Phylogeny (系统发育)

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 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). 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

不同动物眼睛的发育控制由一套同源的基因（Pax6）控制 蜈蚣

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

Eight principles derived from molecular and evolutionary developmental biology Mosaic pleiotropy Ancestral genetic complexity Functional equivalence of distant orthologs and paralogs Deep homology Infrequent toolkit gene duplication Heterotopy Modularity of cis-regulatory elements Vast regulatory networks Sean B. Carroll, Cell. (2008)

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.”

The genetics of evolutionary adaptation Cis-regulatory mutations Structural mutations Gene duplications Gene deletions E.M. De Robertis, Cell. (2008)

Structural mutations yellow Labrador redhead girl Structural mutations affect the sequence of proteins and play an important role in adaptations,as in the examples of hemoglobin and melanic adaptive mutations.A single amino acid change in globin increases the affinity of hemoglobin for oxygen in high-altitude migrating geese compared to their common low-flying relatives.Melanismhas occurred many times independently and, interestingly, is frequently caused by independent gain-of-function mutations in the 7-transmembrane receptor for melanocortin.loss-of-function mutations in the melanocortin receptor are found in yellow Labradors and human redheads yellow Labrador redhead girl Loss-of-function mutations in the melanocortin receptor are found in yellow Labradors and human redheads

Structural mutations 在果蝇，C端磷酸化的ubx抑制腹部dsl基因的表达及足的产生，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 果蝇 Ultrabithorax (Ubx) protein of the crustacean contains regulatory phosphorylation sites that, when phosphorylated, allow the formation of appendages in the crustacean abdomen. In Drosophila, these phosphorylation sites were lost, so it can not develop limbs in the abdomen. Ronshaugen et al.,Nature. (2002)

Gene duplications In the Xenopus D-V patterning system, the ventral gene BMP4 has a dorsal counterpart in ADMP, and each gene has been placed under opposing transcriptional control, permitting the self-regulation of D-V pattern. De Robertis,Nat. Rev. Mol. Cell Biol. (2006)

Gene duplications Thymopoiesis (胸腺发生) requires the Cooperation of Evolutionary Ancient (cxcl12/cxcr4) and new (ccr9/ccr25) chemokine/receptor pairs. The agnatha (无颌类，如七鳃鳗) do not have thymus. The thymus emerged in the gnathostomata (有颌类) with the duplication of (cxcl12/cxcr4). Bajoghli et al. Cell. (2009)

Gene deletions The albinism phenotype mapped to independent deletions in the Oca2 (ocular and cutaneous albinism-2) gene in different cave populations. Protas et al. Nat. Genet. (2006)

(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) 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。

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.

(5) Developmental constraints "a developmental constraint is a bias on the production of variant phenotypes or a limitation on phenotypic variablilty caused by the structure, character, composition, or dynamics of the developmental system". (Maynard Smith et al, 1985)

(6)Modularity The idea that in animals groups of traits are developmentally integrated within modules has been receiving much attention in evolutionary developmental biology. (Wagner, G. P. & Altenberg, L. (1996) Evolution (Lawrence, Kans.) 50, 967–976)

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) 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

·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 )而忽略基因组中大的、重要的遗传改变的作用。

植物的发育与进化