Common Ancestor Of Metazoans Research Articles

Evolution of the phospho-tyrosine signaling machinery in premetazoan lineages

Multicellular animals use a three-part molecular toolkit to mediate phospho-tyrosine signaling: Tyrosine kinases (TyrK), protein tyrosine phosphatases (PTP), and Src Homology 2 (SH2) domains function, respectively, as "writers," "erasers," and "readers" of phospho-tyrosine modifications. How did this system of three components evolve, given their interdependent function? Here, we examine the usage of these components in 41 eukaryotic genomes, including the newly sequenced genome of the choanoflagellate, Monosiga brevicollis, the closest known unicellular relative to metazoans. This analysis indicates that SH2 and PTP domains likely evolved earliest-a handful of these domains are found in premetazoan eukaryotes lacking tyrosine kinases, most likely to deal with limited tyrosine phosphorylation cross-catalyzed by promiscuous Ser/Thr kinases. Modern TyrK proteins, however, are only observed in two lineages, metazoans and choanoflagellates. These two lineages show a dramatic coexpansion of all three domain families. Concurrent expansion of the three domain families is consistent with a stepwise evolutionary model in which preexisting SH2 and PTP domains were of limited utility until the appearance of the TyrK domain in the last common ancestor of metazoans and choanoflagellates. The emergence of the full three-component signaling system, with its dramatically increased encoding potential, may have contributed to the advent of metazoan multicellularity.

Fungal CSL transcription factors.

BackgroundThe CSL (CBF1/RBP-Jκ/Suppressor of Hairless/LAG-1) transcription factor family members are well-known components of the transmembrane receptor Notch signaling pathway, which plays a critical role in metazoan development. They function as context-dependent activators or repressors of transcription of their responsive genes, the promoters of which harbor the GTG(G/A)GAA consensus elements. Recently, several studies described Notch-independent activities of the CSL proteins.ResultsWe have identified putative CSL genes in several fungal species, showing that this family is not confined to metazoans. We have analyzed their sequence conservation and identified the presence of well-defined domains typical of genuine CSL proteins. Furthermore, we have shown that the candidate fungal protein sequences contain highly conserved regions known to be required for sequence-specific DNA binding in their metazoan counterparts. The phylogenetic analysis of the newly identified fungal CSL proteins revealed the existence of two distinct classes, both of which are present in all the species studied.ConclusionOur findings support the evolutionary origin of the CSL transcription factor family in the last common ancestor of fungi and metazoans. We hypothesize that the ancestral CSL function involved DNA binding and Notch-independent regulation of transcription and that this function may still be shared, to a certain degree, by the present CSL family members from both fungi and metazoans.

Surprisingly complex T‐box gene complement in diploblastic metazoans

Ctenophores and cnidarians are two metazoan groups that evolved at least 600 Ma, predating the Cambrian explosion. Although both groups are commonly categorized as diploblastic animals without derivatives of the mesodermal germ layer, ctenophores possess definitive contractile "muscle" cells. T-box family transcription factors are an evolutionarily ancient gene family, arising in the common ancestor of metazoans, and have been divided into eight groups in five distinct subfamilies, many of which are involved in the specification of mesodermal as well as ectodermally and endodermally derived structures. Here, we report the cloning and expression of five T-box genes from a ctenophore, Mnemiopsis leidyi. Phylogenetic analyses demonstrated that ctenophores possess members of at least three of the five T-box subfamilies, and expression studies suggested distinct roles of each T-box genes during gastrulation and early organogenesis. Moreover, genome searches of the sea anemone, Nematostella vectensis (anthozoan cnidarian), showed at least 13 T-box genes in Nematostella, which are divided into at least six distinct groups in the same three subfamilies found in ctenophores. Our results from two diploblastic animals indicate that the common ancestor of eumetazoans had a complex set of T-box genes and that two distinct subfamilies might have appeared during triploblastic evolution.

Nervous and muscle system development in Phascolion strombus (Sipuncula)

Recent interpretations of developmental gene expression patterns propose that the last common metazoan ancestor was segmented, although most animal phyla show no obvious signs of segmentation. Developmental studies of non-model system trochozoan taxa may shed light on this hypothesis by assessing possible cryptic segmentation patterns. In this paper, we present the first immunocytochemical data on the ontogeny of the nervous system and the musculature in the sipunculan Phascolion strombus. Myogenesis of the first anlagen of the body wall ring muscles occurs synchronously and not subsequently from anterior to posterior as in segmented spiralian taxa (i.e. annelids). The number of ring muscles remains constant during the initial stages of body axis elongation. In the anterior-posteriorly elongated larva, newly formed ring muscles originate along the entire body axis between existing myocytes, indicating that repeated muscle bands do not form from a posterior growth zone. During neurogenesis, the Phascolion larva expresses a non-metameric, paired, ventral nerve cord that fuses in the mid-body region in the late-stage elongated larva. Contrary to other trochozoans, Phascolion lacks any larval serotonergic structures. However, two to three FMRFamide-positive cells are found in the apical organ. In addition, late larvae show commissure-like neurones interconnecting the two ventral nerve cords, while early juveniles exhibit a third, medially placed FMRFamidergic ventral nerve. Although we did not find any indications for cryptic segmentation, certain neuro-developmental traits in Phascolion resemble the conditions found in polychaetes (including echiurans) and myzostomids and support a close relationship of Sipuncula and Annelida.

A simple plan--cnidarians and the origins of developmental mechanisms.

Comparisons with cnidarians, long considered to be ‘simple’ animals, are providing crucial insights into the origins of conserved developmental mechanisms and the nature of the common metazoan ancestor. Traditionally, an extra germ layer and a second axis of body symmetry are the features that distinguish ‘higher’ Metazoa from lower animals such as cnidarians. Moreover, it was expected that ‘lower’ animals would have a simple gene set that corresponds to their simple morphology. Now, molecular genetic approaches are blurring the developmental divide between cnidarians and bilateral animals, and cnidarian sequencing projects are showing that the common metazoan ancestor was more genetically complex than was previously assumed.

EST Analysis of the Cnidarian Acropora millepora Reveals Extensive Gene Loss and Rapid Sequence Divergence in the Model Invertebrates

A significant proportion of mammalian genes are not represented in the genomes of Drosophila, Caenorhabditis or Saccharomyces, and many of these are assumed to have been vertebrate innovations. To test this assumption, we conducted a preliminary EST project on the anthozoan cnidarian, Acropora millepora, a basal metazoan. More than 10% of the Acropora ESTs with strong metazoan matches to the databases had clear human homologs but were not represented in the Drosophila or Caenorhabditis genomes; this category includes a surprising diversity of transcription factors and metabolic proteins that were previously assumed to be restricted to vertebrates. Consistent with higher rates of divergence in the model invertebrates, three-way comparisons show that most Acropora ESTs match human sequences much more strongly than they do any Drosophila or Caenorhabditis sequence. Gene loss has thus been much more extensive in the model invertebrate lineages than previously assumed and, as a consequence, some genes formerly thought to be vertebrate inventions must have been present in the common metazoan ancestor. The complexity of the Acropora genome is paradoxical, given that this organism contains apparently few tissue types and the simplest extant nervous system consisting of a morphologically homogeneous nerve net.

Origin of the Metazoan Immune System: Identification of the Molecules and Their Functions in Sponges

During the evolutionary transition to Metazoa, cell-cell- as well as cell-matrix recognition molecules have been formed, which made a further step in evolution possible, the establishment of an immune system. Sponges [Porifera] represent the oldest still extant metazoan phylum and consequently testify to major features of the common metazoan ancestor, the Urmetazoa. Most studies with respect to evolution and phylogeny in sponges have been performed with the marine demosponges Suberites domuncula and Geodia cydonium. These animals possess effective defense systems against microbes and parasites which involve engulfment of bacteria into specific cells, but also signal transduction pathways which actively kill bacteria. Among those is the LPS-mediated pathway, with the stress-responsive kinases. In addition, sponges are provided with an interferon-related system, with the (2-5)A synthetase as controlling enzyme. Transplantation studies have been performed on tissue, as well as at the cellular level ("mixed sponge cell reaction assay") which demonstrate the complex molecular strategy by which sponges respond to allogeneic- and/or autogeneic signals. Among the molecules involved in histo(in)compatibility response of sponges, cytokines e.g., the allograft inflammatory factor 1, have been identified which control rejection of allografts. Furthermore, transcription factors, with Tcf-like factor as an example, have been identified which very likely control gene expression during histocompatibility reactions. The immune reactions in sponges can be modulated by FK506, a drug which has been successfully used as immunosuppressant in humans. One further surprising finding is the fact that G. cydonium has several molecules containing polymorphic Ig-like domains of the variable type. It is concluded that the successful evolutionary transition to the Metazoa, with the sponges as the oldest still extant phylum, and the subsequent rapid radiation into the other metazoan phyla, became possible because of the acquisition of modular molecules, involved in cell adhesion and the immune system.

The Origin of Metazoan Complexity: Porifera as Integrated Animals

Sponges [Porifera] are the phylogenetically oldest metazoan phylum still extant today; they share the closest relationship with the hypothetical common metazoan ancestor, the Urmetazoa. During the past 8 years cDNAs coding for proteins involved in cell-cell- and cell-tissue interaction have been cloned from sponges, primarily from Suberites domuncula and Geodia cydonium and their functions have been studied in vivo as well as in vitro. Also, characteristic elements of the extracellular matrix have been identified and cloned. Those data confirmed that all metazoan phyla originate from one ancestor, the Urmetazoa. The existence of cell adhesion molecules allowed the emergence of a colonial organism. However, for the next higher stage in evolution, individuation, two further innovations had to be formed: the immune- and the apoptotic system. Major defense pathways/molecules to prevent adverse effects against microbes/parasites have been identified in sponges. Furthermore, key molecules of the apoptotic pathway(s), e.g., the pro-apoptotic molecule comprising two death domains, the executing enzyme caspases, as well as the anti-apoptotic/cell survival proteins belonging to the Bcl-2 family have been identified and cloned from sponges. Based on these results-primarily obtained through a molecular biological approach-it is concluded that cell-cell- and cell-matrix adhesion systems were required for the transition to a colonial stage of organization, while the development of an immune system as well as of apoptotic processes were prerequisites for reaching the integrated stage. As the latter stage already exists in sponges, it is therefore likely that the hypothetical ancestor, the Urmetazoa, was also an "integrated colony."

Protein evolution: structure‐function relationships of the oncogene beta‐catenin in the evolution of multicellular animals

Beta-catenin functions as a cytoskeletal linker protein in cadherin-mediated adhesion and as a signal mediator in wnt-signal transduction pathways. We use a novel integrative approach, combining evolutionary, genomic, and three-dimensional structural data to analyze and trace the structural and functional evolution of beta-catenin genes. This approach also enabled us to examine the effects of gene duplication on the structure and function of beta-catenin genes in Drosophila, C. elegans, and vertebrates. By sampling a large number of different taxa, we identified both ancestral and derived motifs and residues within the different regions of the beta-catenin proteins. Projecting amino acid substitutions onto the three- dimensional structure established for mouse beta-catenin, we identified specific domains that exhibit loss and gain of selective constraints during beta catenin evolution. Structural changes, changes in the amino acid substitution rate, and the appearance of novel functional domains in beta-catenin can be mapped to specific branches on the metazoan tree. Together, our analyses suggest that a single, beta-catenin gene fulfilled both adhesion and signaling functions in the last common ancestor of metazoans some 700 million years ago. In addition, gene duplications facilitated the evolution of beta-catenins with novel functions and allowed the evolution of multiple, single-function proteins (cell adhesion or wnt-signaling) from the ancestral, dual-function protein. Integrative methods such as those we have applied here, utilizing the 'natural experiments' present in animal diversity, can be employed to identify novel and shared functional motifs and residues in virtually any protein among the proteomes of model systems and humans.

The Nemertodermatida are basal bilaterians and not members of the Platyhelminthes

Recent hypotheses on metazoan phylogeny have recognized three main clades of bilaterian animals: Deuterostomia, Ecdysozoa and Lophotrochozoa. The acoelomate and ‘pseudocoelomate’ metazoans, including the Platyhelminthes, long considered basal bilaterians, have been referred to positions within these clades by many authors. However, a recent study based on ribosomal DNA placed the flatworm group Acoela as the sister group of all other extant bilaterian lineages. Unexpectedly, the nemertodermatid flatworms, usually considered the sister group of the Acoela together forming the Acoelomorpha, were grouped separately from the Acoela with the rest of the Platyhelminthes (the Rhabditophora) within the Lophotrochozoa. To re‐evaluate and clarify the phylogenetic position of the Nemertodermatida, new sequence data from 18S ribosomal DNA and mitochondrial genes of nemertodermatid and other bilaterian species were analysed with parsimony and maximum likelihood methods. The analyses strongly support a basal position within the Bilateria for the Nemertodermatida as a sister group to all other bilaterian taxa except the Acoela. Despite the basal position of both Nemertodermatida and Acoela, the clade Acoelomorpha was not retrieved. These results imply that the last common ancestor of bilaterian metazoans was a small, benthic, direct developer without segments, coelomic cavities, nephrida or a true brain. The name Nephrozoa is proposed for the ancestor of all bilaterians excluding the Nemertodermatida and the Acoela, and its descendants.

The radial‐symmetric hydra and the evolution of the bilateral body plan: an old body became a young brain

The radial symmetric cnidarians are regarded as being close to the common metazoan ancestor before bilaterality evolved. It is proposed that a large fraction of the body of this gastrula-like organism gave rise to the head of more evolved organisms. The trunk was added later in evolution from an unfolding of a narrow zone between the tentacles and the blastoporus. This implies that, counter intuitively, the foot of the hydra corresponds to the most anterior part (forebrain and heart) while the opening of the gastric column gave rise to the anus. Two fundamentally different modes of midline formation evolved. In vertebrates, the organiser attracts cells from the both sides of the marginal zone. These leave the organiser as a unified band. The midline is formed sequentially from anterior to posterior. In insects, the midline forms opposite a dorsal repelling center, i.e., on the ventral side. This can occur more or less simultaneously over the whole anteroposterior extension.

Sponge paraphyly and the origin of Metazoa.

In order to allow critical evaluation of the interrelationships between the three sponge classes, and to resolve the question of mono- or paraphyly of sponges (Porifera), we used the polymerase chain reaction (PCR) to amplify almost the entire nucleic acid sequence of the 18S rDNA from several hexactinellid, demosponge and calcareous sponge species. The amplification products were cloned, sequenced and then aligned with previously reported sequences from other sponges and nonsponge metazoans and variously distant outgroups, and trees were constructed using both neighbour-joining and maximum parsimony methods. Our results suggest that sponges are paraphyletic, the Calcarea being more related to monophyletic Eumetazoa than to the siliceous sponges (Demospongiae, Hexactinellida). These results have important implications for our understanding of metazoan origins, because they suggest that the common ancestor of Metazoa was a sponge. They also have consequences for basal metazoan classification, implying that the phylum Porifera should be abandoned. Our results support the upgrading of the calcareous sponge class to the phylum level.

Receptor protein-tyrosine phosphatases: origin of domains (catalytic domain, Ig-related domain, fibronectin type III module) based on the sequence of the sponge Geodia cydonium

Reversible tyrosine phosphorylation of proteins is one of the major regulatory physiological events in response to cell-cell- and cell-matrix contact in Metazoa. Previously it was documented that the tyrosine phosphorylating enzymes, the tyrosine kinases (TKs), are autapomorphic characters of Metazoa, including sponges. In this paper the tyrosine dephosphorylating enzymes, the protein-tyrosine phosphatases (PTPs), are studied which can be grouped into two subfamilies, the soluble PTPs and the receptor PTPs (RPTPs). PTPs are characterized by one PTPase domain which interestingly comprises sequence similarity to yeast PTPs. In contrast to the PTPs, the RPTPs – which have been found only in Metazoa – are provided with two PTPase domains. To study the evolution of the RPTPs the full-length size RPTP was cloned from the marine demosponge Geodia cydonium, the phylogenetic oldest metazoan taxon. The 3253 bp long sequence has a putative open reading frame coding for a 999 aa long RPTP which is characterized by two fibronectin (type III; FN-III) domains in the extracellular portion, one intracellular immunoglobulin (Ig)-related domain, and two PTPase domains. Phylogenetic analysis revealed that the sponge FN-III domains form the basis of the metazoan FN-III domain with the common metazoan ancestor. The Ig-related, typical metazoan, module is classified to the disulphide lacking Ig members and represents the phylogenetic earliest member of this group. The β-sheet propensity was calculated and the characteristic amino acids are present in the seven β-sheets. The analysis of the two PTPase domains of the sponge RPTP demonstrates that the first domain is closely related to the PTPase domains present in the soluble PTPs, while the second PTPase domain is only distantly related to them. By constructing a rooted phylogenetic cladogram it became overt that the duplication of the PTPase domains must have occurred already in yeast. This interesting finding indicates that two conserved PTPase domains originated from a common ancestor in yeast while the evolutionary novelties, the FN-III domains and the Ig-related module, were added during the transition to the Metazoa. Hence, the tyrosine dephosphorylating enzyme, RPTP, is an example for a modular protein which is composed of ancient modules (PTPase domain[s]) and two metazoan novelties, while the tyrosine phosphorylating enzymes, the TKs, evolved only in Metazoa.