Materials and Methods Som Text Figs. S1 to S4 Tables S1 and S2 References and Notes Hox10 and Hox11 Genes Are Required to Globally Pattern the Mammalian Skeleton
Materials and Methods Som Text Figs. S1 to S4 Tables S1 and S2 References and Notes Hox10 and Hox11 Genes Are Required to Globally Pattern the Mammalian Skeleton
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E A Snell;R. F. Furlong;P. W. H. Holland;B F Lang;C. O 'kelly;T. Nerad;M. W. Gray;G. Burger-G.-B
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E A Snell;R. F. Furlong;P. W. H. Holland;B F Lang;C. O 'kelly;T. Nerad;M. W. Gray;G. Burger-G.-B
真菌和植物），显然缺乏动物用于信号和粘附的许多蛋白质。因此，领鞭毛虫与动物的进化关系更近（4-7），它们表达信号和细胞粘附蛋白同源物，为动物起源的研究提供了更多的信息。在单细胞领鞭毛虫中存在用于细胞粘附和动物信号转导的蛋白质，提示了它们在动物和领鞭毛虫的祖先中的祖先功能的问题。尽管cho-anoflagellate的生活方式明显简单，但动物蛋白的cho-anoflagellate同系物在单细胞环境中可能执行类似的生化功能。例如，TK可以在choanoflagellates中起作用，以检测细胞外环境的变化，正如我们已经通过它们对营养可用性的反应所证明的那样。此外，动物细胞粘附蛋白（例如钙粘蛋白）可能源自祖先蛋白，这些蛋白在接合或集落形成期间稳定原生动物细胞之间的相互作用。在动物中介导细胞附着或防御病原体的蛋白质可能是从识别和捕获猎物所需的蛋白质进化而来的。C-型凝集素可能允许领鞭毛虫区分和捕获不同的细菌物种通过结合特定的糖基显示在细菌细胞壁上。有针对性的操纵choanoflagellates的基因功能将是必要的，以测试这些保守分子的祖先的角色的假设。我们只采集了一小部分后囊藻蛋白质组。预测在细胞相互作用中起作用的领鞭藻蛋白的多样性表明，通过对整个领鞭藻基因组进行测序，将发现与动物专有的其他蛋白。特别感兴趣的是转录因子的库和调节动物细胞分化和发育的蛋白质家族的潜在代表性。这样就有可能确定，将基于受体的信号输入与基因调控和细胞行为联系起来的整个调控途径是否早于动物的起源。和人类基因组已经揭示了一组蛋白质结构域，这些结构域在双体动物中是保守的，而在酵母中是不存在的（25，26）。然而，因为双体动物代表后生动物中的最近衍生物，而真菌在向多细胞过渡之前很久就从动物谱系中分化出来，所以仅限于真菌和双体动物基因组的比较并不能揭示祖先动物基因组的复杂性。奥尔兹的协助与图形; J.霍尔特的计算支持;和B。赫什和C.马龙对手稿的批判性阅读。N.K.由NIH博士后奖学金（GM-20734）和C.T.H.老鼠...
fungi, and plants), apparently lack many proteins used by animals for sig-naling and adhesion. Therefore, choanoflagel-lates, with their closer evolutionary relationship to animals (4–7) and their expression of signal-ing and cell adhesion protein homologs, are more informative for studies of animal origins. The existence in unicellular choanoflagel-lates of proteins used for cell adhesion and signal transduction in animals prompts the question of their ancestral function in the progenitor of animals and choanoflagellates. Despite the apparent simplicity of the cho-anoflagellate lifestyle, it is possible that cho-anoflagellate homologs of animal proteins perform similar biochemical functions within a unicellular context. For instance, TKs may act in choanoflagellates to detect changes in the extracellular environment, as we have demonstrated through their response to nutrient availability. In addition, animal cell adhesion proteins, such as the cadherins, may derive from ancestral proteins that stabilized the interactions between protozoan cells during conjugation or colony formation. Proteins that mediate cell attachment or defense against pathogens in animals may have evolved from proteins required for prey recognition and capture. C-type lectins might allow choanoflagellates to distinguish between and capture different bacterial species by binding specific sugar groups displayed on bacterial cell walls. Targeted manipulations of gene function in choanoflagellates will be necessary to test hypotheses about the ancestral roles of these conserved molecules. We have sampled just a fraction of the choanoflagellate proteome. The diversity of choanoflagellate proteins predicted to function in cell interactions suggests that additional proteins shared exclusively with animals will be discovered through sequencing the entire choanoflagellate genome. Of particular interest will be the repertoire of transcription factors and the potential representation of families of proteins that regulate cell differentiation and development in animals. It may then be possible to determine whether entire regulatory pathways linking receptor-based signaling inputs to gene regulation and cell behavior predate the origin of animals. and human genomes have revealed a set of protein domains conserved among Bilateria and absent from yeast (25, 26). However, because the Bilateria represent a recent derivation within the Metazoa and the Fungi diverged from the animal lineage long before the transition to multicellularity, comparisons limited to fungal and bilaterian animal genomes do not reveal the complexity of the ancestral animal genome. Olds for assistance with graphics; J. Holt for computing support; and B. Hersh and C. Malone for critical reading of the manuscript. N.K. is supported by an NIH postdoctoral fellowship (GM-20734) and C.T.H. Mice …