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The principle of continuity demands the existence of prior molecular states and common ancestors responsible for extant macromolecular structure. Here, we focus on the emergence and evolution of loop prototypes - the elemental architects of protein domain structure. Phylogenomic reconstruction spanning superkingdoms and viruses generated an evolutionary chronology of prototypes with six distinct evolutionary phases defining a most parsimonious evolutionary progression of cellular life. Each phase was marked by strategic prototype accumulation shaping the structures and functions of common ancestors. The last universal common ancestor (LUCA) of cells and viruses and the last universal cellular ancestor (LUCellA) defined stem lines that were structurally and functionally complex. The evolutionary saga highlighted transformative forces. LUCA lacked biosynthetic ribosomal machinery, while the pivotal LUCellA lacked essential DNA biosynthesis and modern transcription. Early proteins therefore relied on RNA for genetic information storage but appeared initially decoupled from it, hinting at transformative shifts of genetic processing. Urancestral loop types suggest advanced folding designs were present at an early evolutionary stage. An exploration of loop geometric properties revealed gradual replacement of prototypes with α-helix and ß-strand bracing structures over time, paving the way for the dominance of other loop types. AlphFold2-generated atomic models of prototype accretion described patterns of fold emergence. Our findings favor a ?processual' model of evolving stem lines aligned with Woese's vision of a communal world. This model prompts discussing the 'problem of ancestors' and the challenges that lie ahead for research in taxonomy, evolution and complexity.
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Intrinsic disorder accounts for the flexibility of protein loops, molecular building blocks that are largely responsible for the processes and molecular functions of the living world. While loops likely represent early structural forms that served as intermediates in the emergence of protein structural domains, their origin and evolution remain poorly understood. Here, we conduct a phylogenomic survey of disorder in loop prototypes sourced from the ArchDB classification. Tracing prototypes associated with protein fold families along an evolutionary chronology revealed that ancient prototypes tended to be more disordered than their derived counterparts, with ordered prototypes developing later in evolution. This highlights the central evolutionary role of disorder and flexibility. While mean disorder increased with time, a minority of ordered prototypes exist that emerged early in evolutionary history, possibly driven by the need to preserve specific molecular functions. We also revealed the percolation of evolutionary constraints from higher to lower levels of organization. Percolation resulted in trade-offs between flexibility and rigidity that impacted prototype structure and geometry. Our findings provide a deep evolutionary view of the link between structure, disorder, flexibility, and function, as well as insights into the evolutionary role of intrinsic disorder in loops and their contribution to protein structure and function.
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The structures and functions of proteins are embedded into the loop scaffolds of structural domains. Their origin and evolution remain mysterious. Here, we use a novel graph-theoretical approach to describe how modular and non-modular loop prototypes combine to form folded structures in protein domain evolution. Phylogenomic data-driven chronologies reoriented a bipartite network of loops and domains (and its projections) into 'waterfalls' depicting an evolving 'elementary functionome' (EF). Two primordial waves of functional innovation involving founder 'p-loop' and 'winged-helix' domains were accompanied by an ongoing emergence and reuse of structural and functional novelty. Metabolic pathways expanded before translation functionalities. A dual hourglass recruitment pattern transferred scale-free properties from loop to domain components of the EF network in generative cycles of hierarchical modularity. Modeling the evolutionary emergence of the oldest P-loop and winged-helix domains with AlphFold2 uncovered rapid convergence towards folded structure, suggesting that a folding vocabulary exists in loops for protein fold repurposing and design.
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Dermatitis , Humanos , Desarrollo Embrionario , Filogenia , Dominios Proteicos , TraduccionesRESUMEN
Recruitment is a pervasive activity of life that is at the center of novelty generation and persistence. Without recruitment, novelties cannot spread and biological systems cannot maintain identity through time. Here we explore the problem of identity and change unfolding in space and time. We illustrate recruitment operating at different timescales with metabolic networks, protein domain makeup, the functionome, and the rise of viral 'variants of concern' during the coronavirus disease 2019 (COVID-19) pandemic. We define persistence within a framework of fluxes of matter-energy and information and signal processing in response to internal and external challenges. A 'triangle of persistence' describing reuse, innovation and stasis defines a useful polytope in a phase space of trade-offs between economy, flexibility and robustness. We illustrate how the concept of temporal parts embraced by the perdurantist school provides a processual 4-dimensional 'worm' view of biology that is historical and atemporal. This view is made explicit with chronologies and evolving networks inferred with phylogenomic methodologies. Exploring the origin and evolution of the ribosome reveals recruitment of helical segments and/or large fragments of interacting rRNA molecules in a unification process of accretion that is counteracted by diversification. A biphasic (bow-tie) theory of module generation models this frustrated dynamics. Finally, we further elaborate on a theory of entanglement that takes advantage of the dimensionality reduction offered by holographic principles to propose that short and long-distance interactions are responsible for the increasingly granular and tangled structure of biological systems.
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COVID-19 , Humanos , FilogeniaRESUMEN
BACKGROUND: Sesame is an ancient oilseed crop, known for its high oil content and quality. Its sensitivity to drought at early seedling stage is one of the limiting factors affecting its world-wide growth and productivity. Among plant specific transcription factors, the association of HD-ZIPs with sesame drought responses at early seedling stage is not well-established yet and is very important to develop our molecular understanding on sesame drought tolerance. METHODS AND RESULTS: In this study, total 61 sesame HD-ZIP proteins were identified, based on their protein sequence homology with Arabidopsis and protein domain(s) architecture prediction, followed by their phylogenetic, conserved domain(s) motifs and gene structure analyses to classify them into four classes (HD-ZIP Class I-IV). HD-ZIP Class I was also subdivided into four subgroups: α (SiHZ25, SiHZ43, SiHZ9 and SiHZ16), ß1 (SiHZ10, SiHZ30, SiHZ32 and SiHZ26), ß2 (SiHZ42 and SiHZ45) and γ (SiHZ17, SiHZ7 and SiHZ35) by a comparative phylogenetic analysis of sesame with Arabidopsis and maize. Afterwards, twenty-one days old sesame seedlings were exposed to drought stress by withholding water for 7 days (when soil moisture content reduced to ~16%) and gene expression of HD-ZIP Class I (13 members) was performed in well- watered (control) and drought stressed seedlings. The gene expression analysis showed that the expressions of SiHZ7 (6.8 fold) and SiHZ35 (2.6 fold) from γ subgroup were significantly high in drought seedlings. CONCLUSIONS: This study is useful in demonstrating the role of SiHD-ZIP Class I in sesame drought responses at early seedling stage and to develop its novel drought tolerant varieties.
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Sesamum , Deshidratación/genética , Deshidratación/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/genética , Genoma de Planta , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantones/genética , Plantones/metabolismo , Sesamum/genética , Sesamum/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Seasonal behaviour is an attribute of many viral diseases. Like other 'winter' RNA viruses, infections caused by the causative agent of COVID-19, SARS-CoV-2, appear to exhibit significant seasonal changes. Here we discuss the seasonal behaviour of COVID-19, emerging viral phenotypes, viral evolution, and how the mutational landscape of the virus affects the seasonal attributes of the disease. We propose that the multiple seasonal drivers behind infectious disease spread (and the spread of COVID-19 specifically) are in 'trade-off' relationships and can be better described within a framework of a 'triangle of viral persistence' modulated by the environment, physiology, and behaviour. This 'trade-off' exists as one trait cannot increase without a decrease in another. We also propose that molecular components of the virus can act as sensors of environment and physiology, and could represent molecular culprits of seasonality. We searched for flexible protein structures capable of being modulated by the environment and identified a galectin-like fold within the N-terminal domain of the spike protein of SARS-CoV-2 as a potential candidate. Tracking the prevalence of mutations in this structure resulted in the identification of a hemisphere-dependent seasonal pattern driven by mutational bursts. We propose that the galectin-like structure is a frequent target of mutations because it helps the virus evade or modulate the physiological responses of the host to further its spread and survival. The flexible regions of the N-terminal domain should now become a focus for mitigation through vaccines and therapeutics and for prediction and informed public health decision making.
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INTRODUCTION: While the origin and evolution of proteins remain mysterious, advances in evolutionary genomics and systems biology are facilitating the historical exploration of the structure, function and organization of proteins and proteomes. Molecular chronologies are series of time events describing the history of biological systems and subsystems and the rise of biological innovations. Together with time-varying networks, these chronologies provide a window into the past. AREAS COVERED: Here, we review molecular chronologies and networks built with modern methods of phylogeny reconstruction. We discuss how chronologies of structural domain families uncover the explosive emergence of metabolism, the late rise of translation, the co-evolution of ribosomal proteins and rRNA, and the late development of the ribosomal exit tunnel; events that coincided with a tendency to shorten folding time. Evolving networks described the early emergence of domains and a late 'big bang' of domain combinations. EXPERT OPINION: Two processes, folding and recruitment appear central to the evolutionary progression. The former increases protein persistence. The later fosters diversity. Chronologically, protein evolution mirrors folding by combining supersecondary structures into domains, developing translation machinery to facilitate folding speed and stability, and enhancing structural complexity by establishing long-distance interactions in novel structural and architectural designs.
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Evolución Molecular , Proteoma , Genómica , Humanos , Filogenia , Pliegue de Proteína , Proteoma/genéticaRESUMEN
The canonical view of a 3-domain (3D) tree of life was recently challenged by the discovery of Asgardarchaeota encoding eukaryote signature proteins (ESPs), which were treated as missing links of a 2-domain (2D) tree. Here we revisit the debate. We discuss methodological limitations of building trees with alignment-dependent approaches, which often fail to satisfactorily address the problem of ''gaps.'' In addition, most phylogenies are reconstructed unrooted, neglecting the power of direct rooting methods. Alignment-free methodologies lift most difficulties but require employing realistic evolutionary models. We argue that the discoveries of Asgards and ESPs, by themselves, do not rule out the 3D tree, which is strongly supported by comparative and evolutionary genomic analyses and vast genomic and biochemical superkingdom distinctions. Given uncertainties of retrodiction and interpretation difficulties, we conclude that the 3D view has not been falsified but instead has been strengthened by genomic analyses. In turn, the objections to the 2D model have not been lifted. The debate remains open. Also see the video abstract here: https://youtu.be/-6TBN0bubI8.
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Archaea , Eucariontes , Archaea/genética , Evolución Biológica , Células Eucariotas , Evolución Molecular , FilogeniaRESUMEN
The canonical frameworks of viral evolution describe viruses as cellular predecessors, reduced forms of cells, or entities that escaped cellular control. The discovery of giant viruses has changed these standard paradigms. Their genetic, proteomic and structural complexities resemble those of cells, prompting a redefinition and reclassification of viruses. In a previous genome-wide analysis of the evolution of structural domains in proteomes, with domains defined at the fold superfamily level, we found the origins of viruses intertwined with those of ancient cells. Here, we extend these data-driven analyses to the study of fold families confirming the co-evolution of viruses and ancient cells and the genetic ability of viruses to foster molecular innovation. The results support our suggestion that viruses arose by genomic reduction from ancient cells and validate a co-evolutionary 'symbiogenic' model of viral origins.
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Evolución Biológica , ADN Viral/genética , Genoma Viral , Virus Gigantes/genética , Filogenia , Proteínas Virales/genética , Archaea/genética , Archaea/virología , Bacterias/genética , Bacterias/virología , ADN Viral/química , Eucariontes/genética , Eucariontes/virología , Tamaño del Genoma , Virus Gigantes/clasificación , Proteogenómica/métodos , Proteoma/genética , Proteínas Virales/químicaRESUMEN
Enzyme recruitment is a fundamental evolutionary driver of modern metabolism. We see evidence of recruitment at work in the metabolic Molecular Ancestry Networks (MANET) database, an online resource that integrates data from KEGG, SCOP and structural phylogenomic reconstruction. The database, which was introduced in 2006, traces the deep history of the structural domains of enzymes in metabolic pathways. Here we release version 3.0 of MANET, which updates data from KEGG and SCOP, links enzyme and PDB information with PDBsum, and traces evolutionary information of domains defined at fold family level of SCOP classification in metabolic subnetwork diagrams. Compared to SCOP folds used in the previous versions, fold families are cohesive units of functional similarity that are highly conserved at sequence level and offer a 10-fold increase of data entries. We surveyed enzymatic, functional and catalytic site distributions among superkingdoms showing that ancient enzymatic innovations followed a biphasic temporal pattern of diversification typical of module innovation. We grouped enzymatic activities of MANET into a hierarchical system of subnetworks and mesonetworks matching KEGG classification. The evolutionary growth of these modules of metabolic activity was studied using bipartite networks and their one-mode projections at enzyme, subnetwork and mesonetwork levels of organization. Evolving metabolic networks revealed patterns of enzyme sharing that transcended mesonetwork boundaries and supported the patchwork model of metabolic evolution. We also explored the scale-freeness, randomness and small-world properties of evolving networks as possible organizing principles of network growth and diversification. The network structure shows an increase in hierarchical modularity and scale-free behavior as metabolic networks unfold in evolutionary time. Remarkably, this evolutionary constraint on structure was stronger at lower levels of metabolic organization. Evolving metabolic structure reveals a 'principle of granularity', an evolutionary increase of the cohesiveness of lower-level parts of a hierarchical system. MANET is available at http://manet.illinois.edu.
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Algoritmos , Biología Computacional/métodos , Evolución Molecular , Almacenamiento y Recuperación de la Información , Redes y Vías Metabólicas , Proteínas/metabolismo , Gráficos por Computador , Bases de Datos de Proteínas , Humanos , Filogenia , Proteínas/clasificaciónRESUMEN
Networks describe how parts associate with each other to form integrated systems which often have modular and hierarchical structure. In biology, network growth involves two processes, one that unifies and the other that diversifies. Here, we propose a biphasic (bow-tie) theory of module emergence. In the first phase, parts are at first weakly linked and associate variously. As they diversify, they compete with each other and are often selected for performance. The emerging interactions constrain their structure and associations. This causes parts to self-organize into modules with tight linkage. In the second phase, variants of the modules diversify and become new parts for a new generative cycle of higher level organization. The paradigm predicts the rise of hierarchical modularity in evolving networks at different timescales and complexity levels. Remarkably, phylogenomic analyses uncover this emergence in the rewiring of metabolomic and transcriptome-informed metabolic networks, the nanosecond dynamics of proteins, and evolving networks of metabolism, elementary functionomes, and protein domain organization.