Antoine Danchin

Li Kashing Faculty of Medicine University of Hong Kong

The experimental design of a minimal synthetic genome revealed the presence of a large number of genes without ascribed function, in part because the abstract laws of life must be implemented within ad hoc material contraptions. Creating a function needs recruitment of some pre-existing structure and this reveals kludges in their set-up and history...

How do ageing bacterial colonies generate adaptive mutants? Over a period of two months, we isolated on ageing colonies outgrowing mutants able to use a new carbon source, and sequenced their genomes. This allowed us to uncover exquisite details on the molecular mechanism behind their adaptation: most mutations were located in just a few hotspots i...

Genomic studies focus on key metabolites and pathways that, despite their obvious anthropocentric design, keep being 'predicted', while this is only finding again what is already known. As increasingly more genomes are sequenced, this lightpost effect may account at least in part for our failure to understand the function of a continuously growing...

In the context of the COVID-19 pandemic, we describe here the singular metabolic background that constrains enveloped RNA viruses to evolve towards likely attenuation in the long term, possibly after a step of increased pathogenicity. Cytidine triphosphate (CTP) is at the crossroad of the processes allowing SARS-CoV-2 to multiply, because CTP is in...

Assembly of minimal genomes revealed many genes encoding unknown functions. Three overlooked functional categories account for some of them. Cells are prone to make errors and age. As a first key function, discrimination between proper and changed entities is indispensable. Discrimination requires management of information, an authentic, yet abstra...

Thymidylate kinases (TMPKs) play an essential role in DNA biosynthesis across all domains of life by catalyzing dTMP phosphorylation to dTDP. In Pseudomonas putida KT2440, a model Gram-negative soil bacterium, tmk is disrupted by a 65-kb genomic island (GI), posing questions about the origin of the essential TMPK function. To solve this long-standi...

Science is founded on a method based on critical thinking. A prerequisite for this is not only a sufficient command of language but also the comprehension of the basic concepts underlying our understanding of reality. This constraint implies an awareness of the fact that the truth of the World is not directly accessible to us, but can only be glimp...

The vast majority of genomic sequences are automatically annotated using various software programs. The accuracy of these annotations depends heavily on the very few manual annotation efforts that combine verified experimental data with genomic sequences from model organisms. Here, we summarize the updated functional annotation of Bacillus subtilis...

The interplay between the virus, infected cells and immune responses to SARS-CoV-2 is still under debate. By extending the basic model of viral dynamics, we propose here a formal approach to describe neutralisation versus weak (or non-)neutralisation scenarios and compare them with the possible effects of antibody-dependent enhancement (ADE). The t...

Pasteur’s originality in the way he developed pure research is to have understood the importance, for society, of the underlying motivation. Curiosity, of course, is a strong motivation, which explains why we seek to understand the origin of life. But, in front of the immensity of the possible choices, why not, also, choose to start from questions...

Queuosine (Q) is a conserved hypermodification of the wobble base of tRNA containing GUN anticodons but the physiological consequences of Q deficiency are poorly understood in bacteria. This work combines transcriptomic, proteomic and physiological studies to characterize a Q-deficient Escherichia coli K12 MG1655 mutant. The absence of Q led to inc...

Over the last 25 years, biology has entered the genomic era and is becoming a science of ‘big data’. Most interpretations of genomic analyses rely on accurate functional annotations of the proteins encoded by more than 500 000 genomes sequenced to date. By different estimates, only half the predicted sequenced proteins carry an accurate functional...

In this paper, we describe the biochemical reconstitution of a cysteine salvage pathway and the biochemical characterization of each of the five enzymes involved. The salvage begins with amine acetylation of S-alkylcysteine, followed by thioether oxidation. The C-S bond of the resulting sulfoxide is cleaved using a new flavoenzyme catalytic motif t...

basis of modern computation is the formal description of a finite state machine, the Universal Turing Machine, based on manipulation of integers and logic symbols. In this contribution to the discourse on the computer-brain analogy, we discuss the extent to which analog computing, as performed by the mammalian brain, is like and unlike the digital...

It has been reported that multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) including Alpha, Beta, Gamma, and Delta can reduce neutralization by antibodies, resulting in vaccine breakthrough infections. Virus–antiserum neutralization assays are typically performed to monitor potential vaccine breakthro...

Reduced substrates produced by the serpentinization reaction under hydration of olivine may have fuelled biological processes on early Earth. To understand the adaptive strategies and carbon metabolism of the microbes in the serpentinizing ecosystems, we reconstructed 18 draft genomes representing dominant species of Omnitrophicaeota, Gammaproteoba...

It has been reported that multiple SARS-CoV-2 variants of concerns (VOCs) including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) can reduce neutralisation by antibodies, resulting in vaccine breakthrough infections. Virus-antiserum neutralisation assays are typically performed to monitor potential vaccine breakthrough strains...

The evolution of microorganisms often involves changes of unclear relevance, such as transient phenotypes and sequential development of multiple adaptive mutations in hotspot genes. Previously, we showed that ageing colonies of an E. coli mutant unable to produce cAMP when grown on maltose, accumulated mutations in the crp gene (encoding a global t...

Living systems are studied using three complementary approaches: living cells, cell‐free systems and computer‐mediated modelling. Progresses in understanding, allowing researchers to create novel chassis and industrial processes rest on a cycle that combines in vivo, in vitro and in silico studies. This design–build–test–learn iteration loop cycle...

Growing evidence suggests that human gut bacteria, which comprise the microbiome, are linked to several neurodegenerative disorders. An imbalance in the bacterial population in the gut of Parkinson’s disease (PD) and Alzheimer’s disease (AD) patients has been detected in several studies. This dysbiosis very likely decreases or increases microbiome-...

The operon model was proposed six decades ago. And yet, despite all this time, the lactose operon repressor, LacI, remains a subject of major interest. While it is well established that LacI can exist in two functional forms, one that renders the operon inactive via binding of LacI to DNA and another, bound to an inducer that does not allow repress...

The Covid-19 pandemic has required nonpharmaceutical interventions, primarily physical distancing, personal hygiene and face mask use, to limit community transmission, irrespective of seasons. In fact, the seasonality attributes of this pandemic remain one of its biggest unknowns. Early studies based on past experience from respiratory diseases foc...

The global propagation of SARS‐CoV‐2 and the detection of a large number of variants, some of which have replaced the original clade to become dominant, underscores the fact that the virus is actively exploring its evolutionary space. The longer high levels of viral multiplication occur – permitted by high levels of transmission –, the more the vir...

How bacteria adjust gene expression to cope with variable environments remains open to question. Here, we investigated the way global gene expression changes in E. coli correlated with the metabolism of seven carbon substrates chosen to trigger a large panel of metabolic pathways. Coarse‐grained analysis of gene co‐expression identified a novel reg...

Growing evidence suggests that human gut bacteria, comprising the microbiome that communicates with the brain through the so-called ‘gut-brain-axis’, are linked to neurodegenerative disorders. Imbalances in the microbiome of Parkinson’s disease (PD) and Alzheimer’s disease (AD) patients have been detected in several studies. Queuine is a hypermodif...

Background: Starting late 2019, a novel coronavirus spread from the capital of the Hubei province in China to the rest of the country, then to most of the world. To anticipate future trends in the development of the pandemic, we explore here, based on public records of infected persons, how variation in the virus tropism could end up in different...

The interplay between the virus, infected cells and the immune responses to SARS-CoV-2 is still under debate. Extending the basic model of viral dynamics we propose here a formal approach to describe the neutralizing versus non-neutralizing scenarios and compare with the possible effects of antibody-dependent enhancement (ADE). The theoretical mode...

Motivated by historical and present clinical observations, we discuss the possible unfavorable evolution of the immunity (similar to documented antibody-dependent enhancement scenarios) after a first infection with COVID-19. More precisely we ask the question of how the epidemic outcomes are affected if the initial infection does not provide immuni...

In the fight against the spread of COVID-19 the emphasis is on vaccination or on reactivating existing drugs used for other purposes. The tight links that necessarily exist between the virus as it multiplies and the metabolism of its host are systematically ignored. Here we show that the metabolism of all cells is coordinated by the availability of...

The Covid-19 pandemic has spread across the world during early 2020, with unforeseen consequences. Beyond social measures and biomedical research, it is important to assess the seasonality of the epidemic to inform strategies, with limited available data in the short period of time between the March equinox and the June solstice. While the effect o...

Fighting the COVID-19 epidemic summons deep understanding of the way SARS-CoV-2 taps into its host cell metabolic resources. We describe here the singular metabolic background that creates a bottleneck constraining coronaviruses to evolve towards likely attenuation in the long term. Cytidine triphosphate (CTP) is at the crossroad of the biosyntheti...

Background: The metabolic capacity, stress response and evolution of uncultured environmental Tenericutes have remained elusive, since previous studies have been largely focused on pathogenic species. In this study, we expanded analyses on Tenericutes lineages that inhabit various environments using a collection of 840 genomes. Results: Several...

Motivated by historical and present clinical observations, we discuss the possible unfavorable evolution of the immunity (similar to documented antibody-dependent enhancement scenarios) after a first infection with COVID-19. More precisely we ask the question of how the epidemic outcomes are affected if the initial infection does not provide immuni...

We have recently argued that, because microbes have pervasive – often vital – influences on our lives, and that therefore their roles must be taken into account in many of the decisions we face, society must become microbiology‐literate, through the introduction of relevant microbiology topics in school curricula (Timmis et al. 2019. Environ Microb...

The origins of the SARS‐CoV‐2 virus remains enigmatic. It is likely to be a continuum resulting from inevitable mutations and recombination events. These genetic changes keep developing in the present epidemic. Mutations tending to deplete the genome in its cytosine content will progressively lead to attenuation as a consequence of Muller’s ratchet...

The current SARS‐CoV‐2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID‐19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS‐CoV‐2 infections may, at...

The probability D that a given CRISPR‐based gene drive element contaminates another, non‐target species can be estimated by the following Drive Risk Assessment Quantitative Estimate (DRAQUE) Equation: D = (hyb + transf).express.cut.flank.immune.nonextinct with hyb = probability of hybridization between the target species and a non‐target species tr...

Background: A novel coronavirus spread starting late 2019 from the capital of the Hubei province in China to the rest of the country, then to most of the world. To anticipate future trends in the development of the epidemic, we explore here, based on public records of infected persons how variation in the virus tropism could end up in different pat...

Most developments in synthetic biology try to depart from life as we know it, attempting to create orthogonal constructions. Here, following a variational principle, I try to explore how slight changes in the buildup of cells reveal critical features of life's physics. In a first section, I suggest that we use stable isotopes of the atoms of life t...

The translation process, central to life, is tightly connected to the one‐carbon (1‐C) metabolism via a plethora of macromolecule modifications and specific effectors. Using manual genome annotations and putting together a variety of experimental studies, we explore here the possible reasons of this critical interaction, likely to have originated d...

Even when they no longer require the presence of iron, cells use zinc as a divalent cation, involved in a large variety of catalytic and regulatory functions. This metal is so important that it appears that ribosomes are instrumental in its ultimate storage. Here, we summarize a detailed analysis which investigates the way the global cell metabolis...

Background Microbiome biomarker discovery for patient diagnosis, prognosis, and risk evaluation is attracting broad interest. Selected groups of microbial features provide signatures that characterize host disease states such as cancer or cardio-metabolic diseases. Yet, the current predictive models stemming from machine learning still behave as bl...

Background A novel coronavirus (SARS-CoV-2) spread from the capital of the Hubei province in China to the rest of the country, then to most of the world. To anticipate future trends in the development of the epidemic, we explore here, based on public records of infected persons how variation in the virus tropism could end up in different patterns,...

The metabolic capacity, stress response and evolution of uncultured environmental Tenericutes have remained elusive, since previous studies have been largely focused on pathogenic species. In this study, we expanded analyses on Tenericutes lineages that inhabit various environments using a collection of 840 genomes. Several novel environmental line...

Hadal trenches are characterized by not only high hydrostatic pressure but also scarcity of nutrients and high diversity of viruses. Snailfishes, as the dominant vertebrates, play an important role in hadal ecology. Although studies have suggested possible reasons for the tolerance of hadal snailfish to high hydrostatic pressure, little is known ab...

The minimal genome is a theoretical concept asking what is the minimal gene set that defines life under a given environment. Experimental efforts show that stripping off most non-essential genes results in fragile organisms with “minimal genomes”. By contrast, eliminating cryptic genes and mobile DNA results in strains with “minimized genomes” suit...

The presence of most of the atoms involved in the building up of living cells can be explained by their intrinsic physico-chemical properties. Yet, the involvement of the alkali metal potassium cation (K⁺) is somewhat of a mystery for most scenarios of origins of life, as this element is less abundant than its sodium counterpart in sea water, the o...

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translate...

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translate...

The probability D that a given CRISPR-based gene drive element contaminates another, non-target species can be estimated by the following Drive Risk Assessment Quantitative Estimate (DRAQUE) Equation: D = ( hyb+transf).express.cut.flank.immune.nonextinct with hyb = probability of hybridization between the target species and a non-target species tra...

The Escherichia coli cyclic AMP receptor protein (CRP or catabolite activator protein, CAP) provides a textbook example of bacterial transcriptional regulation and is one of the best studied transcription factors in biology. For almost five decades a large number of mutants, evolved in vivo or engineered in vitro, have shed light on the molecular s...

Described in Generation of mutation hotspots in ageing bacterial colonies. Sekowska A, Wendel S, Fischer EC, Nørholm MHH, Danchin A. Sci Rep. 2016 Dec 5;6(1):2. doi: 10.1038/s41598-016-0005-4. PMID: 28442761

Microbes and their activities have pervasive, remarkably profound and generally positive effects on the functioning, and thus health and well‐being, of human beings, the whole of the biological world, and indeed the entire surface of the planet and its atmosphere. Collectively, and to a significant extent in partnership with the sun, microbes are t...

The linguistic foundations of science and technology have relied on a range of terms many of which are borrowed from ancient languages, a known but little researched fact from a statistical perspective. Precise definitions and novel concepts are often crafted with those — frequently used — terms, yet their etymology from Greek or Latin might not al...

The development of synthetic biology calls for accurate understanding of the critical functions that allow construction and operation of a living cell. Besides coding for ubiquitous structures, minimal genomes encode a wealth of functions that dissipate energy in an unanticipated way. Analysis of these functions shows that they are meant to manage...

The linguistic foundations of science and technology include many terms that have been borrowed from ancient languages. In the case of terms with origins in the Greek language, the modern meaning can often differ significantly from the original one. Here we use the PubMed database to demonstrate the prevalence of words of Greek origin in the langua...

The 172 words with rich meaning (nouns, adjectives and verb forms) that appear in at least one million PubMed records. A part-of-speech tagger was used to classify the words under consideration (https://cst.dk/tools/index.php).

A search string containing the 152 words with rich meaning and four or more characters that appear in at least one million PubMed records. The search that excludes the 15 Greek terms is generated automatically at the following URL: https://tinyurl.com/y7kflbcb

The 243 words that appear in at least one million PubMed records.

The 152 words with rich meaning and four or more characters that appear in at least one million PubMed records.

Despite some notable progress in data sharing policies and practices, restrictions are still often placed on the open and unconditional use of various genomic data after they have received official approval for release to the public domain or to public databases. These restrictions, which often conflict with the terms and conditions of the funding...

Despite decades of studies meant to analyse the bacterial response to carbon limitation, we still miss a high‐resolution overview of the situation. All gene expression changes observed in such conditions cannot solely be accounted for by the global regulator Crp either free or bound to its effector, cyclic AMP. Here, for the first time, we evaluate...

Fig. S1. Expression changes of genes enriched in the 10 non‐significantly enriched profiles following growth rates.

Table S1. Transcriptional start site (TSS) of new promoters identified. Table S2. Prediction of Crp‐cAMP binding site at the promoter region of corresponding genes.

Data S1. DEGs identified during carbon limitation.

Data S2. Relative expression of DEGs and their expression patterns following growth rates during carbon limitation.

Data S3. Six groups of genes with various regulatory mechanisms.

Data S4. Genes subjected to GRDC and controlled by other regulators which respond to nitrogen limitation.

Methionine is essential for life. Its chemistry makes it fragile in the presence of oxygen. Aerobic living organisms have selected a salvage pathway (the MSP) that uses dioxygen to regenerate methionine, associated to a ratchet‐like step that prevents methionine back degradation. Here, we describe the variation on this theme, developed across the t...

Regarder plus de trois milliards d’années en arrière est difficile et la reconstruction d’arbres de l’évolution à partir de l’ADN actuel repose sur des hypothèses cachées qui ne permettent pas de retrouver ses vraies racines. Cherchant à s’affranchir de notre anthropocentrisme, le scénario proposé dans les deux textes qui seront successivement publ...

Biomarker discovery using metagenomic data is becoming more prevalent for patient diagnosis, prognosis and risk evaluation. Selected groups of microbial features provide signatures that characterize host disease states such as cancer or cardio-metabolic diseases. Yet, the current predictive models stemming from machine learning still behave as blac...

Unique among animals as they evolved towards Homo sapiens, hominins progressively cooked their food on a routine basis. Cooked products are characterised by singular chemical compounds, derived from the pervasive Maillard reaction. This same reaction is omnipresent in normal metabolism involving carbonyls and amines, and its products accumulate wit...

Science and engineering rely on the accumulation and dissemination of knowledge to make discoveries and create new designs. Discovery‐driven genome research rests on knowledge passed on via gene annotations. In response to the deluge of sequencing big data, standard annotation practice employs automated procedures that rely on majority rules. We ar...

Using functional analysis to explore ways allowing construction of cells from scratch, we analyze the constraints on gene expression created by the physical organization of the genetic program in a live cell chassis. Using a simplified definition of what life is, a split between master functions and helper functions, and the engineering reasoning o...

The position 34 of a tRNA is always modified for efficient recognition of codons and accurate integration of amino acids by the translation machinery. Here, we report genomics features of a deep-sea gut symbiotic Spiroplasma, which suggests that the organism does not require tRNA(34) anticodon modifications. In the genome, there is a novel set of t...

Genome annotation is, nowadays, performed via automatic pipelines that cannot discriminate between right and wrong annotations. Given their importance in increasing the accuracy of the genome annotations of other organisms, it is critical that the annotations of model organisms reflect the current annotation gold standard. The genome of Bacillus su...

Looking for a common origin of all things is pervasive. This is reflected in the idea of a common clock ticking in parallel with evolution. Yet, two stages mark any form of life, multiplication and being alive without multiplying. Also, constructing more biomass puts together at least three space dimensions: the cell volume, its membranes and its g...

Table S1. The extended Bacillus subtilis paleome

Appendix S1. Experimental identification of methylthioribose transport and a missing step in lysine biosynthesis.

Table S2. Bacillus subtilis 168 annotated genome in the EMBL‐ENA format.

Protective symbiosis has been reported in many organisms, but the molecular mechanisms of the mutualistic interactions between the symbionts and their host are unclear. Here, we sequenced the 424-Kbp genome of “ Candidatus Spiroplasma holothuricola” that dominated the hindgut microbiome of a sea cucumber, a major scavenger captured in the Mariana t...

Our communication discusses the profound impact of bio-based economies – in particular microbial biotechnologies – on SDG 8: Promote sustained, inclusive and sustainable economic growth, full and productive employment and decent work for all. A bio-based economy provides significant potential for improving labour supply, education and investment, a...