Early Multicellular Organisms Research Articles

Paleontology: Ediacaran ecology drove ocean ventilation

Fluid dynamics modeling of an Ediacaran ecosystem illustrates an important positive feedback loop between early multicellular organisms and environmental water flow. Early communities thus helped to chemically shape new environments where oxygen-dependent organisms could thrive.

Growth produces coordination trade-offs in Trichoplax adhaerens, an animal lacking a central nervous system

How collectives remain coordinated as they grow in size is a fundamental challenge affecting systems ranging from biofilms to governments. This challenge is particularly apparent in multicellular organisms, where coordination among a vast number of cells is vital for coherent animal behavior. However, the earliest multicellular organisms were decentralized, with indeterminate sizes and morphologies, as exemplified by Trichoplax adhaerens, arguably the earliest-diverged and simplest motile animal. We investigated coordination among cells in T. adhaerens by observing the degree of collective order in locomotion across animals of differing sizes and found that larger individuals exhibit increasingly disordered locomotion. We reproduced this effect of size on order through a simulation model of active elastic cellular sheets and demonstrate that this relationship is best recapitulated across all body sizes when the simulation parameters are tuned to a critical point in the parameter space. We quantify the trade-off between increasing size and coordination in a multicellular animal with a decentralized anatomy that shows evidence of criticality and hypothesize as to the implications of this on the evolution hierarchical structures such as nervous systems in larger organisms.

The Transcriptome and Proteome Networks of Malignant Tumours Reveal Atavistic Attractors of Polyploidy-Related Asexual Reproduction

The expression of gametogenesis-related (GG) genes and proteins, as well as whole genome duplications (WGD), are the hallmarks of cancer related to poor prognosis. Currently, it is not clear if these hallmarks are random processes associated only with genome instability or are programmatically linked. Our goal was to elucidate this via a thorough bioinformatics analysis of 1474 GG genes in the context of WGD. We examined their association in protein-protein interaction and coexpression networks, and their phylostratigraphic profiles from publicly available patient tumour data. The results show that GG genes are upregulated in most WGD-enriched somatic cancers at the transcriptome level and reveal robust GG gene expression at the protein level, as well as the ability to associate into correlation networks and enrich the reproductive modules. GG gene phylostratigraphy displayed in WGD+ cancers an attractor of early eukaryotic origin for DNA recombination and meiosis, and one relative to oocyte maturation and embryogenesis from early multicellular organisms. The upregulation of cancer-testis genes emerging with mammalian placentation was also associated with WGD. In general, the results suggest the role of polyploidy for soma-germ transition accessing latent cancer attractors in the human genome network, which appear as pre-formed along the whole Evolution of Life.

The Consequences of Budding versus Binary Fission on Adaptation and Aging in Primitive Multicellularity.

Early multicellular organisms must gain adaptations to outcompete their unicellular ancestors, as well as other multicellular lineages. The tempo and mode of multicellular adaptation is influenced by many factors including the traits of individual cells. We consider how a fundamental aspect of cells, whether they reproduce via binary fission or budding, can affect the rate of adaptation in primitive multicellularity. We use mathematical models to study the spread of beneficial, growth rate mutations in unicellular populations and populations of multicellular filaments reproducing via binary fission or budding. Comparing populations once they reach carrying capacity, we find that the spread of mutations in multicellular budding populations is qualitatively distinct from the other populations and in general slower. Since budding and binary fission distribute age-accumulated damage differently, we consider the effects of cellular senescence. When growth rate decreases with cell age, we find that beneficial mutations can spread significantly faster in a multicellular budding population than its corresponding unicellular population or a population reproducing via binary fission. Our results demonstrate that basic aspects of the cell cycle can give rise to different rates of adaptation in multicellular organisms.

Transmissible cancers and the evolution of sex under the Red Queen hypothesis.

The predominance of sexual reproduction in eukaryotes remains paradoxical in evolutionary theory. Of the hypotheses proposed to resolve this paradox, the 'Red Queen hypothesis' emphasises the potential of antagonistic interactions to cause fluctuating selection, which favours the evolution and maintenance of sex. Whereas empirical and theoretical developments have focused on host-parasite interactions, the premises of the Red Queen theory apply equally well to any type of antagonistic interactions. Recently, it has been suggested that early multicellular organisms with basic anticancer defences were presumably plagued by antagonistic interactions with transmissible cancers and that this could have played a pivotal role in the evolution of sex. Here, we dissect this argument using a population genetic model. One fundamental aspect distinguishing transmissible cancers from other parasites is the continual production of cancerous cell lines from hosts' own tissues. We show that this influx dampens fluctuating selection and therefore makes the evolution of sex more difficult than in standard Red Queen models. Although coevolutionary cycling can remain sufficient to select for sex under some parameter regions of our model, we show that the size of those regions shrinks once we account for epidemiological constraints. Altogether, our results suggest that horizontal transmission of cancerous cells is unlikely to cause fluctuating selection favouring sexual reproduction. Nonetheless, we confirm that vertical transmission of cancerous cells can promote the evolution of sex through a separate mechanism, known as similarity selection, that does not depend on coevolutionary fluctuations.

How geometry shapes division of labor.

A mathematical model shows how the shape of early multicellular organisms may have helped cells evolve specialized roles.

Glacial origin of the Cryogenian Nantuo Formation in eastern Shennongjia area (South China): Implications for macroalgal survival

The Cryogenian Period was characterized by global glaciations, imposing extreme environmental stresses on early multicellular organisms. Globally distributed diamictite deposits are the major evidence for these glaciation events, but the glacial origin of at least some of these diamictite deposits has been disputed, complicating interpretations of the environmental conditions influencing the evolution of life in the Cryogenian (~720–635 Ma). In this study, we conducted a systematic sedimentological investigation of the Marinoan-age (~650–635 Ma) Nantuo Formation in six sections representing a ~20-km-long, east–west transect in the eastern Shennongjia area of South China. The Nantuo Formation, which ranges in thickness from ~2 m in the east to ~300 m in the west, comprises diamictite, conglomerate, lonestone-bearing sandstone, green siltstone, and black shale facies. The eastern sections (e.g., Longxi and Wushanhu) consist mainly of diamictite facies exhibiting micro-scaled rotation structures, microshear, grain stacking, grain-to-grain contacts and water-escape structures, supporting their deposition in a subglacial setting. In contrast, the western sections (Shijiahe, Liziping and Songluo) consist of massive and graded diamictite and conglomerate facies, consistent with an origin as glacially induced submarine debris flows. Furthermore, the lonestone-bearing sandstone facies in these sections contain abundant dropstones and mud pellets within finely-laminated turbidites, indicating an ice-rafted origin with locally reworking by turbidity currents. The green siltstone and black shale facies lack glacigenic features and may represent late deglacial deposits. Based on thickness and facies variations among the study sections, we infer that the Nantuo Formation records glacial sedimentation on a complex paleotopographic surface that was incised into the underlying bedrock, with subglacial deposits to the east transitioning into glaciomarine deposits to the west of study area. The distal Songluo section likely records three cycles of glacial advance and retreat in the form of a facies alternation between diamictite and black shale, consistent with a dynamically fluctuating ice margin. In summary, our sedimentological investigation supports a glacial origin for the Nantuo Formation in the eastern Shennongjia area. The occurrence of the benthic macroalgal-dominated Songluo Biota in the black shale facies at Songluo suggests that strong glacial retreats provided niches for macroalgal survival in the Cryogenian glacial ocean.

P53 Functions in Adipose Tissue Metabolism and Homeostasis.

As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms to humans. A function not directly related to tumor suppression, such as the regulation of metabolism in nontransformed cells, could explain this selective pressure. While this role of p53 in cellular metabolism is gradually emerging, it is imperative to dissect the tissue- and cell-specific actions of p53 and its downstream signaling pathways. In this review, we focus on studies reporting p53’s impact on adipocyte development, function, and maintenance, as well as the causes and consequences of altered p53 levels in white and brown adipose tissue (AT) with respect to systemic energy homeostasis. While whole body p53 knockout mice gain less weight and fat mass under a high-fat diet owing to increased energy expenditure, modifying p53 expression specifically in adipocytes yields more refined insights: (1) p53 is a negative regulator of in vitro adipogenesis; (2) p53 levels in white AT are increased in diet-induced and genetic obesity mouse models and in obese humans; (3) functionally, elevated p53 in white AT increases senescence and chronic inflammation, aggravating systemic insulin resistance; (4) p53 is not required for normal development of brown AT; and (5) when p53 is activated in brown AT in mice fed a high-fat diet, it increases brown AT temperature and brown AT marker gene expression, thereby contributing to reduced fat mass accumulation. In addition, p53 is increasingly being recognized as crucial player in nutrient sensing pathways. Hence, despite existence of contradictory findings and a varying density of evidence, several functions of p53 in adipocytes and ATs have been emerging, positioning p53 as an essential regulatory hub in ATs. Future studies need to make use of more sophisticated in vivo model systems and should identify an AT-specific set of p53 target genes and downstream pathways upon different (nutrient) challenges to identify novel therapeutic targets to curb metabolic diseases.

Methylation specific targeting of a chromatin remodeling complex from sponges to humans

DNA cytosine methylation and methyl-cytosine binding domain (MBD) containing proteins are found throughout all vertebrate species studied to date. However, both the presence of DNA methylation and pattern of methylation varies among invertebrate species. Invertebrates generally have only a single MBD protein, MBD2/3, that does not always contain appropriate residues for selectively binding methylated DNA. Therefore, we sought to determine whether sponges, one of the most ancient extant metazoan lineages, possess an MBD2/3 capable of recognizing methylated DNA and recruiting the associated nucleosome remodeling and deacetylase (NuRD) complex. We find that Ephydatia muelleri has genes for each of the NuRD core components including an EmMBD2/3 that selectively binds methylated DNA. NMR analyses reveal a remarkably conserved binding mode, showing almost identical chemical shift changes between binding to methylated and unmethylated CpG dinucleotides. In addition, we find that EmMBD2/3 and EmGATAD2A/B proteins form a coiled-coil interaction known to be critical for the formation of NuRD. Finally, we show that knockdown of EmMBD2/3 expression disrupts normal cellular architecture and development of E. muelleri. These data support a model in which the MBD2/3 methylation-dependent functional role emerged with the earliest multicellular organisms and has been maintained to varying degrees across animal evolution.

LRRFIP家族的研究进展

LRRFIP蛋白是能与富含亮氨酸重复序列的FLI (flightless I)蛋白相互作用的分子，参与许多生物学过程，包括作为转录抑制因子抑制TNFα以及NFκB的活性，能与其他蛋白相互作用调控Wnt/β-catenin信号通路进而参与细胞骨架的重排以及作为胞质内外源核酸感受器参与抗病毒过程等。系统进化分析显示，高等哺乳动物中的LRRFIP1和LRRFIP2，以及鱼类中LRRFIP1a，LRRFIP1b和LRRFIP2都是由早期多细胞动物中单一的原始的LRRFIP进化而来。 LRRFIPs was originated as proteins interacting with leucine-rich repeat flightless I gene (FLI); it is involved many functions, including acting as a transcriptional repressor to inhibit TNFα and NFκB activity, interacting with other proteins to regulate Wnt/β-catenin signaling pathway for cytoskel-eton rearrangement, and function as cytosolic nucleic acid sensor against exogenous virus. Phylo-genetic analysis revealed that LRRFIP1 and LRRFIP2 in mammals, LRRFIP1a, LRRFIP1b and LRRFIP2 in fishes are all evolved from single proto LRRFIP in early multicellular organisms.

Energy metabolism and behavior in the corticotropin-releasing factor family of peptides.

Energy metabolism and behavior in the corticotropin-releasing factor family of peptides.

Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms.

Basement membranes are highly specialized extracellular matrices. Once considered inert scaffolds, basement membranes are now viewed as dynamic and versatile environments that modulate cellular behaviors to regulate tissue development, function, and repair. Increasing evidence suggests that, in addition to providing structural support to neighboring cells, basement membranes serve as reservoirs of growth factors that direct and fine-tune cellular functions. Type IV collagens are a major component of all basement membranes. They evolved along with the earliest multicellular organisms and have been integrated into diverse fundamental biological processes as time and evolution shaped the animal kingdom. The roles of basement membranes in humans are as complex and diverse as their distributions and molecular composition. As a result, basement membrane defects result in multisystem disorders with ambiguous and overlapping boundaries that likely reflect the simultaneous interplay and integration of multiple cellular pathways and processes. Consequently, there will be no single treatment for basement membrane disorders, and therapies are likely to be as varied as the phenotypes. Understanding tissue-specific pathology and the underlying molecular mechanism is the present challenge; personalized medicine will rely upon understanding how a given mutation impacts diverse cellular functions.

The heyday of paleontology in China

Life is the most exquisite and splendid natural outcome on our planet. Life has arisen as an evolutionary experiment of the continually and erratically changing earth system that has persisted for the 4.5 billion years since the formation of this planet. The enormous biodiversity we see today represents a small fraction of the life that has ever existedonearth.As the ‘luckiest’ andmost intelligent species of all beings, we humans, with our unique and consciousminds, have never stopped inquiring where andwhen we came from. Our curious eyes look into deep time to understand the history of life. By unearthing and examining fossils, which are traces and petrified remains left behind by prehistoric organisms, paleontology deciphers the biological messages of past organisms written in rocks of different ages and interprets the direct testimony of the changing earth system in the grand dimensions of time and space. Paleontology is the discipline that bridges biology and geology. Fossils were known early in human history, and their meaning was interpreted in various ways by western wisdom and by Chinese naturalists for over 2000 years. Paleontology as a scientific discipline, however, took its shape in the 18th century in Europe and grew quickly during the 19th century. After Charles Darwin published the On the Origin of Species in 1859, paleontology as a school of natural sciences refocused on understanding the evolutionary path of life. Along with developments in geology, biology, and modern technology in the 19th and 20th centuries, the traditional practice of paleontology using morphology, taxonomy, and biochronology evolved into a form that is equipped with multidisciplinary approaches and is technically and methodologically sophisticated. New concepts, theories, andmethods that developed alongwith the appearance and progress of plate tectonics, radiometric dating, stable isotopic studies, and molecular biology, are now blended into the bloodof traditional paleontology. Searching for themechanisms behind the diversification of life, mass extinctions, and the paleoenvironmental background, paleontology has been brought to a new stage in which organisms and their surroundings have become a single multifaceted research subject commonly tackled by joint international teamwork. In such an enriched intellectual atmosphere, on the ground laid by generations of scientists, and chargedwith the energy of a promising economy, paleontology in China has blossomed into a strong basic research enterprise during the last two decades. We have been fortunate to have witnessed and been involved in this unprecedented development. We use this special topic of National Science Review as an opportunity to bring together a collection of essays that briefly highlights some of the most remarkable paleontological work accomplished during the last two decades in China, with the hope that this will encourage greater endeavors in future research. China contains rich and unique fossil resources, such as the Precambrian Weng’an Biota, the early Cambrian Chengjiang Biota, and the Early Cretaceous Jehol Biota, to name but a few. Numerous important fossils, someofwhich are considered to be ‘missing links’ in the chain of organismal evolution, have been discovered in the strata of various geologic time intervals. Research on these fossils has significantly advanced our knowledge of the history of life as a whole.The presentations included in the special topic of this issue encompass a spectrum of subjects: from the evolution of the earliest multicellular organisms to how birds conquered the sky, from the coevolution of parasites and hosts to the origin of flowering plants, from insights into genomes and fossils to the early evolution ofmammals, and from an overview of the Jehol Biota to the largest scale mass extinction on earth, in which death resulted in a new flourishing of life. The focus in most of these articles is on critical transitions in organisms and the earth system over geological time. Because paleontological studies in China are so diverse and publications have poured out at such a rapid pace in recent years, the articles included in this special topic are understandably far from being comprehensive. Discoveries are forever, and our efforts to search for the history of life are endless. What has been achieved in paleontology in China is undoubtedly superb, but it is only the opening statement of an influential speech; much remains to be said in the decades to come.The great potential for research opportunities needs to be cultivated and numerous scientific problems remain to be solved. Looking into the history of life, we see a bright future for the study of paleontology in China and the rest of the world. Finally, we thank all the contributors, reviewers, and editorial staff for their time and dedication that made this special topic possible.

To Fuse or Not to Fuse? An Evolutionary View of Self-Recognition Systems

Self-recognition systems preventing chimera formation following somatic fusion between members of the same species have evolved only in certain phyla (e.g., fungi, cnidarians, poriferans, bryozoans, urochordates). We present here some of the biological features common to fungi and colonial marine invertebrates, which may have driven the evolution of such self-recognition systems. We conclude that the evolution of self-recognition mechanisms in fusible organisms is more likely to result from a complex trade-off between selection pressures linked with a gregariousness and sessile way of life. This trade-off also raises the question of how extrinsic interactions between a group of cooperative cells and its direct environment may have driven the evolution towards a form of individuality, via the emergence self-recognition systems in fusible organisms. Gregariousness and sessility being two features intrinsically associated emergence of multicellularity, somatic incompatibility systems could then be considered as one of the first expressions of individuality in early multicellular organisms.

The Lantian biota: A new window onto the origin and early evolution of multicellular organisms

The Lantian biota at the Lantian Town of Xiuning County, Anhui Province, is preserved in black shales of the Ediacaran Lantian Formation. It yields some of the oldest known complex macroorganisms, including fan-shaped seaweeds and possible animal fossils with tentacles and intestinal-like structures reminiscent of modern coelenterates and bilaterians. The Lantian Lagerstätte sheds new light on the origin and early evolution of multicellular organisms in relatively quiet and deep environments soon after the Neoproterozoic Marinoan glaciation. The morphological complexity and diversity of early multicellular organisms may be closely related to sexual reproduction and alternation of generations. The fluctuation of oceanic redox conditions during this period may have played a role in the ecology and preservation of the Lantian biota.

Evolution of the Heart from Bacteria to Man

This review provides an overview of the evolutionary path to the mammalian heart from the beginnings of life (about four billion years ago ) to the present. Essential tools for cellular homeostasis and for extracting and burning energy are still in use and essentially unchanged since the appearance of the eukaryotes. The primitive coelom, characteristic of early multicellular organisms ( approximately 800 million years ago), is lined by endoderm and is a passive receptacle for gas exchange, feeding, and sexual reproduction. The cells around this structure express genes homologous to NKX2.5/tinman, and gradual specialization of this "gastroderm" results in the appearance of mesoderm in the phylum Bilateria, which will produce the first primitive cardiac myocytes. Investment of the coelom by these mesodermal cells forms a "gastrovascular" structure. Further evolution of this structure in the bilaterian branches Ecdysoa (Drosophila) and Deuterostoma (amphioxus) culminate in a peristaltic tubular heart, without valves, without blood vessels or blood, but featuring a single layer of contracting mesoderm. The appearance of Chordata and subsequently the vertebrates is accompanied by a rapid structural diversification of this primitive linear heart: looping, unidirectional circulation, an enclosed vasculature, and the conduction system. A later innovation is the parallel circulation to the lungs, followed by the appearance of septa and the four-chambered heart in reptiles, birds, and mammals. With differentiation of the cardiac chambers, regional specialization of the proteins in the cardiac myocyte can be detected in the teleost fish and amphibians. In mammals, growth constraints are placed on the heart, presumably to accommodate the constraints of the body plan and the thoracic cavity, and adult cardiac myocytes lose the ability to re-enter the cell cycle on demand. Mammalian cardiac myocyte innervation betrays the ancient link between the heart, the gut, and reproduction: the vagus nerve controlling heart rate emanates from centers in the central nervous system regulating feeding and affective behavior.

Light on ancient photoreceptors

Early multicellular organisms had two distinct types of photoreceptor cells, apparently with different functions. How these cells combined to form modern eyes turns out to be a complicated story.

Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses.

Heat shock proteins are abundant soluble intracellular proteins, present in all cells. Members of the heat shock protein family bind peptides including antigenic peptides generated within cells. Heat shock proteins also interact with antigen presenting cells through CD91 and other receptors, eliciting a cascade of events including re-presentation of heat shock protein-chaperoned peptides by MHC, translocation of NF kappa B into the nuclei and maturation of dendritic cells. These consequences point to a key role of heat shock proteins in fundamental immunological phenomena such as activation of antigen presenting cells, indirect presentation (or cross-priming), and chaperoning of peptides during antigen presentation. Heat shock proteins appear to have been involved in innate immune responses since the emergence of phagocytes in early multicellular organisms and to have been commandeered for adaptive immune responses with the advent of specificity. These properties of heat shock proteins also allow them to be used for immunotherapy of cancers and infections in novel ways.

Carbohydrate self-recognition mediates marine sponge cellular adhesion.

Sponges (Porifera), the simplest and earliest multicellular organisms, are thought to have evolved from their unicellular ancestors about 1 billion years ago by developing cell-recognition and adhesion mechanisms to discriminate against "non-self." Consequently, they are used as models for investigating recognition phenomena. Cellular adhesion of marine sponges is an event involving adherence of extracellular proteoglycan-like molecules, otherwise known as aggregation factors (AFs). In a calcium-independent process the AFs adhere to the cell surface, and in a calcium-dependent process they exhibit AF self-association. A mechanism which has been implied but not definitely proven to play a role in the calcium-dependent event is self-recognition of defined carbohydrate epitopes. For the red beard sponge, Microciona prolifera, two carbohydrate epitopes, a sulfated disaccharide and a pyruvylated trisaccharide, have been implicated in cellular adhesion. To investigate this phenomenon a system has been designed, by using surface plasmon resonance detection, to mimic the role of carbohydrates in cellular adhesion of M. prolifera. The results show self-recognition of the sulfated disaccharide to be a major force behind the calcium-dependent event. The interaction is not simply based on electrostatic interactions, as other sulfated carbohydrates analyzed by using this procedure did not self-associate. Furthermore, the interaction is completely eradicated on substitution of Ca(2+) ions by either Mg(2+) or Mn(2+) ions. This physiologically relevant recognition mechanism confirms the existence of true carbohydrate self-recognition, and may have significant implications for the role of carbohydrates in cellular recognition of higher organisms.

Metabolic and membrane-altering toxins, molecular differentiation factors, and pheromones in the evolution and operation of endocrine-signalling systems.

The endocrine systems of vertebrates and higher invertebrates may have evolved functionally from as far back on the evolutionary scale as bacteria and early multicellular organisms and their biological communities, which have been shown to produce a variety of cyclic nucleotides, peptides, fatty acids, prostaglandins and sterols with endocrine-altering effects in primative as well as more highly evolved species.