A Genomic Survey of HECT Ubiquitin Ligases in Eukaryotes Reveals Independent Expansions of the HECT System in Several Lineages

The posttranslational modification of proteins by the ubiquitination pathway is an important regulatory mechanism in eukaryotes. To date, however, studies on the evolutionary history of the proteins involved in this pathway have been restricted to E1 and E2 enzymes, whereas E3 studies have been focused mainly in metazoans and plants. To have a wider perspective, here we perform a genomic survey of the HECT family of E3 ubiquitin-protein ligases, an important part of this posttranslational pathway, in genomes from representatives of all major eukaryotic lineages. We classify eukaryotic HECTs and reconstruct, by phylogenetic analysis, the putative repertoire of these proteins in the last eukaryotic common ancestor (LECA). Furthermore, we analyze the diversity and complexity of protein domain architectures of HECTs along the different extant eukaryotic lineages. Our data show that LECA had six different HECTs and that protein expansion and N-terminal domain diversification shaped HECT evolution. Our data reveal that the genomes of animals and unicellular holozoans considerably increased the molecular and functional diversity of their HECT system compared with other eukaryotes. Other eukaryotes, such as the Apusozoa Thecanomas trahens or the Heterokonta Phytophthora infestans, independently expanded their HECT repertoire. In contrast, plant, excavate, rhodophyte, chlorophyte, and fungal genomes have a more limited enzymatic repertoire. Our genomic survey and phylogenetic analysis clarifies the origin and evolution of different HECT families among eukaryotes and provides a useful phylogenetic framework for future evolutionary studies of this regulatory pathway

Insights into the origin of metazoan filopodia and microvilli.

Filopodia are fine actin-based cellular projections used for both environmental sensing and cell motility, and they are essential organelles for metazoan cells. In this study, we reconstruct the origin of metazoan filopodia and microvilli. We first report on the evolutionary assembly of the filopodial molecular toolkit and show that homologs of many metazoan filopodial components, including fascin and myosin X, were already present in the unicellular or colonial progenitors of metazoans. Furthermore, we find that the actin crosslinking protein fascin localizes to filopodia-like structures and microvilli in the choanoflagellate Salpingoeca rosetta. In addition, homologs of filopodial genes in the holozoan Capsaspora owczarzaki are upregulated in filopodia-bearing cells relative to those that lack them. Therefore, our findings suggest that proteins essential for metazoan filopodia and microvilli are functionally conserved in unicellular and colonial holozoans and that the last common ancestor of metazoans bore a complex and specific filopodial machinery

The Capsaspora genome reveals a complex unicellular prehistory of animals

Suga, Hiroshi et al.-- This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.To reconstruct the evolutionary origin of multicellular animals from their unicellular ancestors, the genome sequences of diverse unicellular relatives are essential. However, only the genome of the choanoflagellate Monosiga brevicollis has been reported to date. Here we completely sequence the genome of the filasterean Capsaspora owczarzaki, the closest known unicellular relative of metazoans besides choanoflagellates. Analyses of this genome alter our understanding of the molecular complexity of metazoans' unicellular ancestors showing that they had a richer repertoire of proteins involved in cell adhesion and transcriptional regulation than previously inferred only with the choanoflagellate genome. Some of these proteins were secondarily lost in choanoflagellates. In contrast, most intercellular signalling systems controlling development evolved later concomitant with the emergence of the first metazoans. We propose that the acquisition of these metazoan-specific developmental systems and the co-option of pre-existing genes drove the evolutionary transition from unicellular protists to metazoans. © 2013 Macmillan Publishers Limited. All rights reserved.H.S. was supported by the Marie Curie Intra-European Fellowship within the 7th European Community Framework Programme. Genome sequencing, assembly and some supporting analysis was supported by grants from the National Human Genome Research Institute (HG003067-05 through HG003067-10), as were C.N., C.R., B.H. and Z.C. B.F.L. and A.J.R. acknowledge financial support through the Canadian Research Chair program. This study was supported by an ICREA contract, a European Research Council Starting Grant (ERC-2007-StG-206883) and a grant (BFU2011-23434) from the Spanish Ministry of the Economy and Competitiveness (MINECO) awarded to I.R.-T. M.V. was supported by CNRS, the Agence Nationale de la Recherche (ANR grant BLAN-0294) and the Institut Universitaire de France.Peer Reviewe

Complex transcriptional regulation and independent evolution of fungal-like traits in a relative of animals

Cell-type specification through differential genome regulation is a hallmark of complex multicellularity. However, it remains unclear how this process evolved during the transition from unicellular to multicellular organisms. To address this question, we investigated transcriptional dynamics in the ichthyosporean Creolimax fragrantissima, a relative of animals that undergoes coenocytic development. We find that Creolimax utilizes dynamic regulation of alternative splicing, long inter-genic non-coding RNAs and co-regulated gene modules associated with animal multicellularity in a cell-type specific manner. Moreover, our study suggests that the different cell types of the three closest animal relatives (ichthyosporeans, filastereans and choanoflagellates) are the product of lineage-specific innovations. Additionally, a proteomic survey of the secretome reveals adaptations to a fungal-like lifestyle. In summary, the diversity of cell types among protistan relatives of animals and their complex genome regulation demonstrates that the last unicellular ancestor of animals was already capable of elaborate specification of cell types.Peer reviewe

What makes an animal? The molecular quest for the origin of the Animal Kingdom

What makes an animal? To find the answer we need to integrate data from disciplines such as phylogenetics, palaeontology, ecology, development, anatomy and physiology, as well as molecular biology and genomics. Knowledge of which groups branched before and after the origin of animals is essential. Recent advances in molecular phylogenetics, together with the discovery of new eukaryotic lineages, have drawn a new picture of the ancestry of animals. The nature of the early diverging animal lineages and the timing of the transition are in a state of flux. Various factors have been linked to this striking transition to multicellularity, including changes in environmental conditions and the ecological interactions between unicellular eukaryotes. The current wealth of genomic data has also shed new light on this question. The analysis of the genome of various close relatives of animals has revealed the importance that recycling of ancient genes into metazoan biological functions played into animal origins. A recent study reconstructing the genome of the last common ancestor of extant animals has unveiled an unprecedented emergence of new genes, highlighting the role of genomic novelty in the origin of metazoans

Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster.

Sequence variants in cis-acting enhancers are important for polygenic disease, but their role in Mendelian disease is poorly understood. Redundancy between enhancers that regulate the same gene is thought to mitigate the pathogenic impact of enhancer mutations. Recent findings, however, have shown that loss-of-function mutations in a single enhancer near PTF1A cause pancreas agenesis and neonatal diabetes. Using mouse and human genetic models, we show that this enhancer activates an entire PTF1A enhancer cluster in early pancreatic multipotent progenitors. This leading role, therefore, precludes functional redundancy. We further demonstrate that transient expression of PTF1A in multipotent progenitors sets in motion an epigenetic cascade that is required for duct and endocrine differentiation. These findings shed insights into the genome regulatory mechanisms that drive pancreas differentiation. Furthermore, they reveal an enhancer that acts as a regulatory master key and is thus vulnerable to pathogenic loss-of-function mutations

On the origin of biological construction, with a focus on multicellularity

Biology is marked by a hierarchical organization: all life consists of cells; in some cases, these cells assemble into groups, such as endosymbionts or multicellular organisms; in turn, multicellular organisms sometimes assemble into yet other groups, such as primate societies or ant colonies. The construction of new organizational layers results from hierarchical evolutionary transitions, in which biological units (e.g., cells) form groups that evolve into new units of biological organization (e.g., multicellular organisms). Despite considerable advances, there is no bottom-up, dynamical account of how, starting from the solitary ancestor, the first groups originate and subsequently evolve the organizing principles that qualify them as new units. Guided by six central questions, we propose an integrative bottom-up approach for studying the dynamics underlying hierarchical evolutionary transitions, which builds on and synthesizes existing knowledge. This approach highlights the crucial role of the ecology and development of the solitary ancestor in the emergence and subsequent evolution of groups, and it stresses the paramount importance of the life cycle: only by evaluating groups in the context of their life cycle can we unravel the evolutionary trajectory of hierarchical transitions. These insights also provide a starting point for understanding the types of subsequent organizational complexity. The central research questions outlined here naturally link existing research programs on biological construction (e.g., on cooperation, multilevel selection, self-organization, and development) and thereby help integrate knowledge stemming from diverse fields of biology

A phylogenetic and proteomic reconstruction of eukaryotic chromatin evolution

Histones and associated chromatin proteins have essential functions in eukaryotic genome organization and regulation. Despite this fundamental role in eukaryotic cell biology, we lack a phylogenetically comprehensive understanding of chromatin evolution. Here, we combine comparative proteomics and genomics analysis of chromatin in eukaryotes and archaea. Proteomics uncovers the existence of histone post-translational modifications in archaea. However, archaeal histone modifications are scarce, in contrast with the highly conserved and abundant marks we identify across eukaryotes. Phylogenetic analysis reveals that chromatin-associated catalytic functions (for example, methyltransferases) have pre-eukaryotic origins, whereas histone mark readers and chaperones are eukaryotic innovations. We show that further chromatin evolution is characterized by expansion of readers, including capture by transposable elements and viruses. Overall, our study infers detailed evolutionary history of eukaryotic chromatin: from its archaeal roots, through the emergence of nucleosome-based regulation in the eukaryotic ancestor, to the diversification of chromatin regulators and their hijacking by genomic parasites.Research in the A.S.-P. group was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 851647) and the Spanish Ministry of Science and Innovation (PGC2018-098210-A-I00). We also acknowledge support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme (Generalitat de Catalunya). C.N. is supported by an FPI PhD fellowship from the Spanish Ministry of Economy, Industry and Competitiveness (MEIC). X.G.-B. is supported by a Juan de la Cierva fellowship (FJC2018-036282-I) from MEIC. I.R.-T. was supported by a European Research Council (grant no. 616960). B.F.L. was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC; RGPIN-2017-05411) and by the ‘Fonds de Recherche Nature et Technologie’, Quebec. P.L.-G. and D.M. were supported by a Moore and Simons foundations grant (GBMF9739) and by European Research Council advanced grants (322669, 787904). Research in the C.S. group was supported by the ERC through project TACKLE (advanced grant no. 695192)

Comparative genomic analysis of the ‘pseudofungus’ Hyphochytrium catenoides

Eukaryotic microbes have three primary mechanisms for obtaining nutrients and energy: phagotrophy, photosynthesis and osmotrophy. Traits associated with the latter two functions arose independently multiple times in the eukaryotes. The Fungi successfully coupled osmotrophy with filamentous growth, and similar traits are also manifested in the Pseudofungi (oomycetes and hyphochytriomycetes). Both the Fungi and the Pseudofungi encompass a diversity of plant and animal parasites. Genome-sequencing efforts have focused on host-associated microbes (mutualistic symbionts or parasites), providing limited comparisons with free-living relatives. Here we report the first draft genome sequence of a hyphochytriomycete ‘pseudofungus’; Hyphochytrium catenoides. Using phylogenomic approaches, we identify genes of recent viral ancestry, with related viral derived genes also present on the genomes of oomycetes, suggesting a complex history of viral coevolution and integration across the Pseudofungi. H. catenoides has a complex life cycle involving diverse filamentous structures and a flagellated zoospore with a single anterior tinselate flagellum. We use genome comparisons, drug sensitivity analysis and high-throughput culture arrays to investigate the ancestry of oomycete/pseudofungal characteristics, demonstrating that many of the genetic features associated with parasitic traits evolved specifically within the oomycete radiation. Comparative genomics also identified differences in the repertoire of genes associated with filamentous growth between the Fungi and the Pseudofungi, including differences in vesicle trafficking systems, cell-wall synthesis pathways and motor protein repertoire, demonstrating that unique cellular systems underpinned the convergent evolution of filamentous osmotrophic growth in these two eukaryotic groups