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Innate immunity in Aedes mosquitoes: from pathogen resistance to shaping the microbiota Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 Bretta Hixson, Robin Chen, Nicolas Buchon
Discussions of host–microbe interactions in mosquito vectors are frequently dominated by a focus on the human pathogens they transmit (e.g. Plasmodium parasites and arboviruses). Underlying the interactions between a vector and its transmissible pathogens, however, is the physiology of an insect living and interacting with a world of bacteria and fungi including commensals, mutualists and primary and
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Evolutionary immunology to explore original antiviral strategies Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 Jean-Luc Imler, Hua Cai, Carine Meignin, Nelson Martins
Over the past 25 years, the field of evolutionary developmental biology (evo–devo) has used genomics and genetics to gain insight on the developmental mechanisms underlying the evolution of morphological diversity of animals. Evo–devo exploits the key insight that conserved toolkits of development (e.g. Hox genes) are used in animals to produce genetic novelties that provide adaptation to a new environment
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When the microbiome shapes the host: immune evolution implications for infectious disease Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 Mark A. Hanson
The microbiome includes both ‘mutualist’ and ‘pathogen’ microbes, regulated by the same innate immune architecture. A major question has therefore been: how do hosts prevent pathogenic infections while maintaining beneficial microbes? One idea suggests hosts can selectively activate innate immunity upon pathogenic infection, but not mutualist colonization. Another idea posits that hosts can selectively
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Cross-talk and mutual shaping between the immune system and the microbiota during an oyster's life Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 Delphine Destoumieux-Garzón, Caroline Montagnani, Luc Dantan, Noémie de San Nicolas, Marie-Agnès Travers, Léo Duperret, Guillaume M. Charrière, Eve Toulza, Guillaume Mitta, Céline Cosseau, Jean-Michel Escoubas
The Pacific oyster Crassostrea gigas lives in microbe-rich marine coastal systems subjected to rapid environmental changes. It harbours a diversified and fluctuating microbiota that cohabits with immune cells expressing a diversified immune gene repertoire. In the early stages of oyster development, just after fertilization, the microbiota plays a key role in educating the immune system. Exposure to
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Novel technologies uncover novel ‘anti’-microbial peptides in Hydra shaping the species-specific microbiome Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 Alexander Klimovich, Thomas C. G. Bosch
The freshwater polyp Hydra uses an elaborate innate immune machinery to maintain its specific microbiome. Major components of this toolkit are conserved Toll-like receptor (TLR)-mediated immune pathways and species-specific antimicrobial peptides (AMPs). Our study harnesses advanced technologies, such as high-throughput sequencing and machine learning, to uncover a high complexity of the Hydra's AMPs
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Photosynthesis and other factors affecting the establishment and maintenance of cnidarian–dinoflagellate symbiosis Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 Cawa Tran, Gabriel R. Rosenfield, Phillip A. Cleves, Cory J. Krediet, Maitri R. Paul, Sophie Clowez, Arthur R. Grossman, John R. Pringle
Coral growth depends on the partnership between the animal hosts and their intracellular, photosynthetic dinoflagellate symbionts. In this study, we used the sea anemone Aiptasia, a laboratory model for coral biology, to investigate the poorly understood mechanisms that mediate symbiosis establishment and maintenance. We found that initial colonization of both adult polyps and larvae by a compatible
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More than a colour; how pigment influences colourblind microbes Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 Gary M. Wessel, Lili Xing, Nathalie Oulhen
Many animals have pigments when they themselves cannot see colour. Perhaps those pigments enable the animal to avoid predators, or to attract mates. Maybe even those pigmented surfaces are hosts for microbes, even when the microbes do not see colour. Do some pigments then serve as a chemical signal for a good or bad microbial substrate? Maybe pigments attract or repel various microbe types? Echinoderms
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The roles of ABCB1/P-glycoprotein drug transporters in regulating gut microbes and inflammation: insights from animal models, old and new Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 Lauren Stoeltje, Jenna K. Luc, Timothaus Haddad, Catherine S. Schrankel
Commensal enteric bacteria have evolved systems that enable growth in the ecologic niche of the host gastrointestinal tract. Animals evolved parallel mechanisms to survive the constant exposure to bacteria and their metabolic by-products. We propose that drug transporters encompass a crucial system to managing the gut microbiome. Drug transporters are present in the apical surface of gut epithelia
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Tethering of soluble immune effectors to mucin and chitin reflects a convergent and dynamic role in gut immunity Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 L. J. Dishaw, G. W. Litman, A. Liberti
The immune system employs soluble effectors to shape luminal spaces. Antibodies are soluble molecules that effect immunological responses, including neutralization, opsonization, antibody-dependent cytotoxicity and complement activation. These molecules are comprised of immunoglobulin (Ig) domains. The N-terminal Ig domains recognize antigen, and the C-terminal domains facilitate their elimination
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The role of animal hosts in shaping gut microbiome variation Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 Elisa Maritan, Andrea Quagliariello, Enric Frago, Tomaso Patarnello, Maria Elena Martino
Millions of years of co-evolution between animals and their associated microbial communities have shaped and diversified the nature of their relationship. Studies continue to reveal new layers of complexity in host–microbe interactions, the fate of which depends on a variety of different factors, ranging from neutral processes and environmental factors to local dynamics. Research is increasingly integrating
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Cereal weevils' antimicrobial peptides: at the crosstalk between development, endosymbiosis and immune response Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 N. Galambos, C. Vincent-Monegat, A. Vallier, N. Parisot, A. Heddi, A. Zaidman-Rémy
Interactions between animals and microbes are ubiquitous in nature and strongly impact animal physiology. These interactions are shaped by the host immune system, which responds to infections and contributes to tailor the associations with beneficial microorganisms. In many insects, beneficial symbiotic associations not only include gut commensals, but also intracellular bacteria, or endosymbionts
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The importance of host physical niches for the stability of gut microbiome composition Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 William B. Ludington
Gut bacteria are prevalent throughout the Metazoa and form complex microbial communities associated with food breakdown, nutrient provision and disease prevention. How hosts acquire and maintain a consistent bacterial flora remains mysterious even in the best-studied animals, including humans, mice, fishes, squid, bugs, worms and flies. This essay visits the evidence that hosts have co-evolved relationships
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Microbiota-derived acetylcholine can promote gut motility in Drosophila melanogaster Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 Yuka Fujita, Hina Kosakamoto, Fumiaki Obata
The gut microbiota is crucial for intestinal health, including gastrointestinal (GI) motility. How commensal bacterial species influence GI motility has not been fully elucidated. A major factor of GI motility is the gut contraction promoting the propulsive movement of orally ingested materials. Here, we developed a method to monitor and quantify gut contractions in living Drosophila melanogaster larvae
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Understanding the factors regulating host–microbiome interactions using Caenorhabditis elegans Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 Anupama Singh, Robert J. Luallen
The Human Microbiome Project was a research programme that successfully identified associations between microbial species and healthy or diseased individuals. However, a major challenge identified was the absence of model systems for studying host–microbiome interactions, which would increase our capacity to uncover molecular interactions, understand organ-specificity and discover new microbiome-altering
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Dual stressors of infection and warming can destabilize host microbiomes Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 J. D. Li, Y. Y. Gao, E. J. Stevens, K. C. King
Climate change is causing extreme heating events and intensifying infectious disease outbreaks. Animals harbour microbial communities, which are vital for their survival and fitness under stressful conditions. Understanding how microbiome structures change in response to infection and warming may be important for forecasting host performance under global change. Here, we evaluated alterations in the
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How infection-triggered pathobionts influence virulence evolution Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 Mathias Franz, Roland R. Regoes, Jens Rolff
Host–pathogen interactions can be influenced by the host microbiota, as the microbiota can facilitate or prevent pathogen infections. In addition, members of the microbiota can become virulent. Such pathobionts can cause co-infections when a pathogen infection alters the host immune system and triggers dysbiosis. Here we performed a theoretical investigation of how pathobiont co-infections affect the
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A new lexicon in the age of microbiome research Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-18 Thomas C. G. Bosch, Martin J. Blaser, Edward Ruby, Margaret McFall-Ngai
At a rapid pace, biologists are learning the many ways in which resident microbes influence, and sometimes even control, their hosts to shape both health and disease. Understanding the biochemistry behind these interactions promises to reveal completely novel and targeted ways of counteracting disease processes. However, in our protocols and publications, we continue to describe these new results using
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Choice of friction coefficient deeply affects tissue behaviour in stochastic epithelial vertex models Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-04 Pilar Guerrero, Ruben Perez-Carrasco
To understand the mechanisms that coordinate the formation of biological tissues, the use of numerical implementations is necessary. The complexity of such models involves many assumptions and parameter choices that result in unpredictable consequences, obstructing the comparison with experimental data. Here, we focus on vertex models, a family of spatial models used extensively to simulate the dynamics
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Stochasticity in genetics and gene regulation Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-04 Veronica van Heyningen
Development from fertilized egg to functioning multi-cellular organism requires precision. There is no precision, and often no survival, without plasticity. Plasticity is conferred partly by stochastic variation, present inherently in all biological systems. Gene expression levels fluctuate ubiquitously through transcription, alternative splicing, translation and turnover. Small differences in gene
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Transcriptional priming and chromatin regulation during stochastic cell fate specification Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-04 Alison J. Ordway, Rina N. Helt, Robert J. JohnstonJr
Stochastic cell fate specification, in which a cell chooses between two or more fates with a set probability, diversifies cell subtypes in development. Although this is a vital process across species, a common mechanism for these cell fate decisions remains elusive. This review examines two well-characterized stochastic cell fate decisions to identify commonalities between their developmental programmes
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A dynamical perspective: moving towards mechanism in single-cell transcriptomics Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-04 Rory J. Maizels
As the field of single-cell transcriptomics matures, research is shifting focus from phenomenological descriptions of cellular phenotypes to a mechanistic understanding of the gene regulation underneath. This perspective considers the value of capturing dynamical information at single-cell resolution for gaining mechanistic insight; reviews the available technologies for recording and inferring temporal
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Control of cell state transitions by post-transcriptional regulation Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-04 Carla Mulas
Cell state transitions are prevalent in biology, playing a fundamental role in development, homeostasis and repair. Dysregulation of cell state transitions can lead to or occur in a wide range of diseases. In this letter, I explore and highlight the role of post-transcriptional regulatory mechanisms in determining the dynamics of cell state transitions. I propose that regulation of protein levels after
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Bet-hedging and variability in plant development: seed germination and beyond Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-04 Katie Abley, Rituparna Goswami, James C. W. Locke
When future conditions are unpredictable, bet-hedging strategies can be advantageous. This can involve isogenic individuals producing different phenotypes, under the same environmental conditions. Ecological studies provide evidence that variability in seed germination time has been selected for as a bet-hedging strategy. We demonstrate how variability in germination time found in Arabidopsis could
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Contributions of transcriptional noise to leukaemia evolution: KAT2A as a case-study Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-04 Cristina Pina
Transcriptional noise is proposed to participate in cell fate changes, but contributions to mammalian cell differentiation systems, including cancer, remain associative. Cancer evolution is driven by genetic variability, with modulatory or contributory participation of epigenetic variants. Accumulation of epigenetic variants enhances transcriptional noise, which can facilitate cancer cell fate transitions
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On epigenetic stochasticity, entropy and cancer risk Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-04 Andrew E. Teschendorff
Epigenetic changes are known to accrue in normal cells as a result of ageing and cumulative exposure to cancer risk factors. Increasing evidence points towards age-related epigenetic changes being acquired in a quasi-stochastic manner, and that they may play a causal role in cancer development. Here, I describe the quasi-stochastic nature of DNA methylation (DNAm) changes in ageing cells as well as
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How do stochastic processes and genetic threshold effects explain incomplete penetrance and inform causal disease mechanisms? Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2024-03-04 Dagan Jenkins
Incomplete penetrance is the rule rather than the exception in Mendelian disease. In syndromic monogenic disorders, phenotypic variability can be viewed as the combination of incomplete penetrance for each of multiple independent clinical features. Within genetically identical individuals, such as isogenic model organisms, stochastic variation at molecular and cellular levels is the primary cause of
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Human socio-cultural evolution in light of evolutionary transitions: introduction to the theme issue Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Yohay Carmel, Ayelet Shavit, Ehud Lamm, Eörs Szathmáry
Human societies are no doubt complex. They are characterized by division of labour, multiple hierarchies, intricate communication networks and transport systems. These phenomena and others have led scholars to propose that human society may be, or may become, a new hierarchical level that may dominate the individual humans within it, similar to the relations between an organism and its cells, or an
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Can sociality facilitate learning of complex tasks? Lessons from bees and flowers Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Tamar Keasar, Odile Pourtallier, Eric Wajnberg
The emergence of animal societies is a major evolutionary transition, but its implications for learning-dependent innovations are insufficiently understood. Bees, with lifestyles ranging from solitary to eusocial, are ideal models for exploring social evolution. Here, we ask how and why bees may acquire a new ‘technology’, foraging on morphologically complex flowers, and whether eusociality facilitates
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Scaffolding individuality: coordination, cooperation, collaboration and community Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 James Griesemer, Ayelet Shavit
Processes of evolutionary transition (ET), becoming part of a new reproducing collective while losing the capacity of independent reproduction, seem difficult to track without circularity, since their features—units of selection, individuality, inheritance at multiple levels (MLS1, MLS2)—are products of one process. We describe ET in a non-circular way, noting kinds of interactions among community
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Steps to individuality in biology and culture Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Dinah R. Davison, Richard E. Michod
Did human culture arise through an evolutionary transition in individuality (ETI)? To address this question, we examine the steps of biological ETIs to see how they could apply to the evolution of human culture. For concreteness, we illustrate the ETI stages using a well-studied example, the evolution of multicellularity in the volvocine algae. We then consider how those stages could apply to a cultural
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Conditions that favour cumulative cultural evolution Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Kaleda K. Denton, Yoav Ram, Marcus W. Feldman
The emergence of human societies with complex language and cumulative culture is considered a major evolutionary transition. Why such a high degree of cumulative culture is unique to humans is perplexing given the potential fitness advantages of cultural accumulation. Here, Boyd & Richerson’s (1996 Why culture is common, but cultural evolution is rare. Proc. Br. Acad.88, 77–93) discrete-cultural-trait
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Cultural specialization as a double-edged sword: division into specialized guilds might promote cultural complexity at the cost of higher susceptibility to cultural loss Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Yotam Ben-Oren, Oren Kolodny, Nicole Creanza
The transition to specialization of knowledge within populations could have facilitated the accumulation of cultural complexity in humans. Specialization allows populations to increase their cultural repertoire without requiring that members of that population increase their individual capacity to accumulate knowledge. However, specialization also means that domain-specific knowledge can be concentrated
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Communication for collaborative computation: two major transitions in human evolution Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Daniel Dor
This paper presents and defends the following theoretical arguments: (1) The uniqueness of the human condition lies in the fact that only humans engage in collaborative computation, where different individuals work together on shared computational challenges. Collaborative computation is the foundation of our cumulative cultures. (2) Collaborative computation requires individuals to engage in instructive
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The interplay of social identity and norm psychology in the evolution of human groups Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Kati Kish Bar-On, Ehud Lamm
People's attitudes towards social norms play a crucial role in understanding group behaviour. Norm psychology accounts focus on processes of norm internalization that influence people's norm-following attitudes but pay considerably less attention to social identity and group identification processes. Social identity theory in contrast studies group identity but works with a relatively thin and instrumental
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Evolutionary ecology of language origins through confrontational scavenging Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 András Szilágyi, Viktor P. Kovács, Tamás Czárán, Eörs Szathmáry
A dynamic model and an agent-based simulation model implementing the assumptions of the confrontational scavenging hypothesis on early protolanguage as an adaptive response of Homo erectus to gradual change in their habitat has been developed and studied. The core assumptions of the hypothesis and the model scenario are the pre-adaptation of our ancestors to occupy the ecological niche that they constructed
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Human major transitions from the perspective of distributed adaptations Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Ehud Lamm, Meir Finkel, Oren Kolodny
Distributed adaptations are cases in which adaptation is dependent on the population as a whole: the adaptation is conferred by a structural or compositional aspect of the population; the adaptively relevant information cannot be reduced to information possessed by a single individual. Possible examples of human-distributed adaptations are song lines, traditions, trail systems, game drive lanes and
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Human cooperation and evolutionary transitions in individuality Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Cathryn Townsend, Joseph V. Ferraro, Heather Habecker, Mark V. Flinn
A major evolutionary transition in individuality involves the formation of a cooperative group and the transformation of that group into an evolutionary entity. Human cooperation shares principles with those of multicellular organisms that have undergone transitions in individuality: division of labour, communication, and fitness interdependence. After the split from the last common ancestor of hominoids
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Can models of evolutionary transition clarify the debates over the Neolithic Revolution? Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Ayelet Shavit, Gonen Sharon
The ‘Neolithic Revolution,’ sometimes referred to as the emergence of agriculture at its earliest in the southern Levant, is the most significant shift in human history, shaping the world we live in today. Yet, after 100 years of study, its major cause, tempo (gradual or revolutionary), and impact of human intentionality remain disputed. Here, we examine the research potential of an evolutionary transition
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The economic superorganism in the complexity of evolution Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Lisi Krall
The transition to grain agriculture restructured human societies, creating a new whole, an economic superorganism. Homo sapiens became expansionary, structurally interdependent in material life, and a duality between them and Earth was created that had not previously existed. Yet H. sapiens are not the only species to make the transition to agriculture. Cross-species comparisons create an opening for
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Evolution of the Okvik/Old Bering Sea culture of the Bering Strait as a major transition Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Anna Marie Prentiss, Cheyenne Laue, Erik Gjesfjeld, Matthew J. Walsh, Megan Denis, Thomas A. Foor
Great transitions are thought to embody major shifts in locus of selection, labour diversification and communication systems. Such expectations are relevant for biological and cultural systems as decades of research has demonstrated similar dynamics within the evolution of culture. The evolution of the Neo-Inuit cultural tradition in the Bering Strait provides an ideal context for examination of cultural
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Human societal development: is it an evolutionary transition in individuality? Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Yohay Carmel
An evolutionary transition in individuality (ETI) occurs when a previously independent organism becomes a lower level unit within a higher hierarchical level (for example, cells in an organism, ants in a colony). Using archaeological and historical accounts from the last 12 000 years, I empirically examine the proposition that human society increasingly functions as a higher hierarchical level within
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The transition from animal to human culture—simulating the social protocell hypothesis Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Claes Andersson, Tamás Czárán
The origin of human cumulative culture is commonly envisioned as the appearance (some 2.0–2.5 million years ago) of a capacity to faithfully copy the know-how that underpins socially learned traditions. While certainly plausible, this story faces a steep ‘startup problem’. For example, it presumes that ape-like early Homo possessed specialized cognitive capabilities for faithful know-how copying and
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Major evolutionary transitions in individuality between humans and AI Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Paul B. Rainey
That humans might undergo future evolutionary transitions in individuality (ETIs) seems fanciful. However, drawing upon recent thinking concerning the origins of properties that underpin ETIs, I argue that certain ETIs are imminently realizable. Central to my argument is recognition that heritable variance in fitness at higher levels of organization can be externally imposed (scaffolded) by specific
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Four reasons for scepticism about a human major transition in social individuality Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-23 Daniel W. McShea
The ‘major transitions in evolution’ are mainly about the rise of hierarchy, new individuals arising at ever higher levels of nestedness, in particular the eukaryotic cell arising from prokaryotes, multicellular individuals from solitary protists and individuated societies from multicellular individuals. Some lists include human societies as a major transition, but based on a comparison with the non-human
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Reactivity and mechanism in chemical and synthetic biology Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Nigel G. J. Richards, Stephen L. Bearne, Yuki Goto, Emily J. Parker
Physical organic chemistry and mechanistic thinking provide a strong intellectual framework for understanding the chemical logic of evolvable informational macromolecules and metabolic transformations in living organisms. These concepts have also led to numerous successes in designing and applying tools to delineate biological function in health and disease, chemical ecology and possible alternative
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Genome mining of cryptic bisabolenes that were biosynthesized by intramembrane terpene synthases from Antrodia cinnamomea Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Ranuka T. Hewage, Cheng-Chung Tseng, Suh-Yuen Liang, Chen-Yu Lai, Hsiao-Ching Lin
Terpenoids represent the largest structural family of natural products (NPs) and have various applications in the pharmaceutical, food and fragrance industries. Their diverse scaffolds are generated via a multi-step cyclization cascade of linear isoprene substrates catalysed by terpene synthases (TPSs). Bisabolene NPs, which are sesquiterpenes (C15), have wide applications in medicines and biofuels
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Orthoester formation in fungal meroterpenoid austalide F biosynthesis Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Takayoshi Awakawa, Wei Liu, Tongxuan Bai, Tomo Taniguchi, Ikuro Abe
Fungal meroterpenoids are important bioactive natural products. Their biosynthetic machineries are highly diverse, and reconstitutions lead to the production of unnatural meroterpenoids. In this study, heterologous gene expression in Aspergillus oryzae and in vitro assays elucidated the biosynthetic pathway of the orthoester-containing fungal meroterpenoid austalide F. Remarkably, the α-ketoglutarate-dependent
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Exploring a chemical scaffold for rapid and selective photoaffinity labelling of non-ribosomal peptide synthetases in living bacterial cells Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Fumihiro Ishikawa, Sho Konno, Yuko Uchiyama, Hideaki Kakeya, Genzoh Tanabe
Non-ribosomal peptide synthetases (NRPSs) biosynthesize many pharmaceuticals and virulence factors. The biosynthesis of these natural peptide products from biosynthetic gene clusters depends on complex regulations in bacteria. However, our current knowledge of NRPSs is based on enzymological studies using full NRPS systems and/or a single NRPS domain in heterologous hosts. Chemical and/or biochemical
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Structure, mechanism and inhibition of anthranilate phosphoribosyltransferase Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Thomas W. Scully, Wanting Jiao, Gerd Mittelstädt, Emily J. Parker
Anthranilate phosphoribosyltransferase catalyses the second reaction in the biosynthesis of tryptophan from chorismate in microorganisms and plants. The enzyme is homodimeric with the active site located in the hinge region between two domains. A range of structures in complex with the substrates, substrate analogues and inhibitors have been determined, and these have provided insights into the catalytic
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Allosteric inhibition of Staphylococcus aureus MenD by 1,4-dihydroxy naphthoic acid: a feedback inhibition mechanism of the menaquinone biosynthesis pathway Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Tamsyn Stanborough, Ngoc Anh Thu Ho, Esther M. M. Bulloch, Ghader Bashiri, Stephanie S. Dawes, Etheline W. Akazong, James Titterington, Timothy M. Allison, Wanting Jiao, Jodie M. Johnston
Menaquinones (MKs) are electron carriers in bacterial respiratory chains. In Staphylococcus aureus (Sau), MKs are essential for aerobic and anaerobic respiration. As MKs are redox-active, their biosynthesis likely requires tight regulation to prevent disruption of cellular redox balance. We recently found that the Mycobacterium tuberculosis MenD, the first committed enzyme of the MK biosynthesis pathway
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Capturing the free energy of transition state stabilization: insights from the inhibition of mandelate racemase Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Stephen L. Bearne
Mandelate racemase (MR) catalyses the Mg2+-dependent interconversion of (R)- and (S)-mandelate. To effect catalysis, MR stabilizes the altered substrate in the transition state (TS) by approximately 26 kcal mol–1 (–ΔGtx), such that the upper limit of the virtual dissociation constant of the enzyme-TS complex is 2 × 10–19 M. Designing TS analogue inhibitors that capture a significant amount of ΔGtx
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A conserved SH3-like fold in diverse putative proteins tetramerizes into an oxidoreductase providing an antimicrobial resistance phenotype Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Claudèle Lemay-St-Denis, Lorea Alejaldre, Zakaria Jemouai, Kiana Lafontaine, Maxime St-Aubin, Katia Hitache, Donya Valikhani, Nuwani W. Weerasinghe, Myriam Létourneau, Christopher J. Thibodeaux, Nicolas Doucet, Christian Baron, Janine N. Copp, Joelle N. Pelletier
We present a potential mechanism for emergence of catalytic activity that is essential for survival, from a non-catalytic protein fold. The type B dihydrofolate reductase (DfrB) family of enzymes were first identified in pathogenic bacteria because their dihydrofolate reductase activity is sufficient to provide trimethoprim (TMP) resistance. DfrB enzymes are described as poorly evolved as a result
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Rethinking nucleic acids from their origins to their applications Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Steven A. Benner
Reviewed are three decades of synthetic biology research in our laboratory that has generated alternatives to standard DNA and RNA as possible informational systems to support Darwinian evolution, and therefore life, and to understand their natural history, on Earth and throughout the cosmos. From this, we have learned that: • the core structure of nucleic acids appears to be a natural outcome of non-biological
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Crystal structures of ‘ALternative Isoinformational ENgineered’ DNA in B-form Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Madhura S. Shukla, Shuichi Hoshika, Steven A. Benner, Millie M. Georgiadis
The first structural model of duplex DNA reported in 1953 by Watson & Crick presented the double helix in B-form, the form that genomic DNA exists in much of the time. Thus, artificial DNA seeking to mimic the properties of natural DNA should also be able to adopt B-form. Using a host–guest system in which Moloney murine leukemia virus reverse transcriptase serves as the host and DNA as the guests
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Molecular elements: novel approaches for molecular building Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Ruowen Wang, Xueqiang Wang, Sitao Xie, Yanyan Zhang, Dingkun Ji, Xiaobing Zhang, Cheng Cui, Jianhui Jiang, Weihong Tan
Classically, a molecular element (ME) is a pure substance composed of two or more atoms of the same element. However, MEs, in the context of this review, can be any molecules as elements bonded together into the backbone of synthetic oligonucleotides (ONs) with designed sequences and functions, including natural A, T, C, G, U, and unnatural bases. The use of MEs can facilitate the synthesis of designer
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Success probability of high-affinity DNA aptamer generation by genetic alphabet expansion Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Michiko Kimoto, Hui Pen Tan, Yaw Sing Tan, Nur Afiqah Binte Mohd Mislan, Ichiro Hirao
Nucleic acid aptamers as antibody alternatives bind specifically to target molecules. These aptamers are generated by isolating candidates from libraries with random sequence fragments, through an evolutionary engineering system. We recently reported a high-affinity DNA aptamer generation method that introduces unnatural bases (UBs) as a fifth letter into the library, by genetic alphabet expansion
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Discovery, implications and initial use of semi-synthetic organisms with an expanded genetic alphabet/code Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Floyd E. Romesberg
Much recent interest has focused on developing proteins for human use, such as in medicine. However, natural proteins are made up of only a limited number of canonical amino acids with limited functionalities, and this makes the discovery of variants with some functions difficult. The ability to recombinantly express proteins containing non-canonical amino acids (ncAAs) with properties selected to
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Perseverance of protein homeostasis despite mistranslation of glycine codons with alanine Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Farah Hasan, Jeremy T. Lant, Patrick O'Donoghue
By linking amino acids to their codon assignments, transfer RNAs (tRNAs) are essential for protein synthesis and translation fidelity. Some human tRNA variants cause amino acid mis-incorporation at a codon or set of codons. We recently found that a naturally occurring tRNASer variant decodes phenylalanine codons with serine and inhibits protein synthesis. Here, we hypothesized that human tRNA variants
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Ribosomal incorporation of negatively charged d-α- and N-methyl-l-α-amino acids enhanced by EF-Sep Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2023-01-11 Takayuki Katoh, Hiroaki Suga
Ribosomal incorporation of d-α-amino acids (dAA) and N-methyl-l-α-amino acids (MeAA) with negatively charged sidechains, such as d-Asp, d-Glu, MeAsp and MeGlu, into nascent peptides is far more inefficient compared to those with neutral or positively charged ones. This is because of low binding affinity of their aminoacyl-transfer RNA (tRNA) to elongation factor-thermo unstable (EF-Tu), a translation
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Editorial concepts in interaction: social engagement and inner experiences Philos. Trans. Royal Soc. B: Biol. Sci. (IF 6.3) Pub Date : 2022-12-26 Anna M. Borghi, Albertyna Osińska, Andreas Roepstorff, Joanna Raczaszek-Leonardi
This theme issue aims to view the literature on concepts through a novel lens, that of social interaction and its influence on inner experiences. It discusses unsolved problems in literature on concepts, emphasizing the distinction between concrete versus abstract concepts and external versus internal grounding. This introductory article reflects the two research streams that the theme aims to bridge—in