African lungfish genome sheds light on the vertebrate water-to-land transition.

Lungfishes are the closest extant relatives of tetrapods and preserve ancestral traits linked with the water-to-land transition. However, their huge genome sizes have hindered understanding of this key transition in evolution. Here, we report a 40-Gb chromosome-level assembly of the African lungfish (Protopterus annectens) genome, which is the largest genome assembly ever reported and has a contig and chromosome N50 of 1.60 Mb and 2.81 Gb, respectively. The large size of the lungfish genome is due mainly to retrotransposons. Genes with ultra-long length show similar expression levels to other genes, indicating that lungfishes have evolved high transcription efficacy to keep gene expression balanced. Together with transcriptome and experimental data, we identified potential genes and regulatory elements related to such terrestrial adaptation traits as pulmonary surfactant, anxiolytic ability, pentadactyl limbs, and pharyngeal remodeling. Our results provide insights and key resources for understanding the evolutionary pathway leading from fishes to humans.

Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome.

The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP.

Metabolic adaptations of tissue-resident immune cells.

Unlike other cells in the body, immune cells have to be able to enter and adapt to life within diverse tissues. Immune cells develop within dedicated immune system organs, such as the bone marrow, thymus and lymphoid tissues, but also inhabit other tissues, wherein they not only provide defense against infection and malignancies but also contribute to homeostatic tissue function. Because different tissues have widely divergent metabolic rates and fuel requirements, this raises interesting questions about the adaptation of immune cells in specific tissues. When immune cells take up residence in different tissues, they develop a transcriptional signature that reflects adaptation to life and function within that tissue. Genes encoding metabolic-pathway proteins are strongly represented within these signatures, reflective of the importance of metabolic adaptation to tissue residence. In this Review, we discuss the available data on the metabolic adaptation of immune cells to life in different tissue sites, within the broader framework of how functional adaptation versus maladaptation in the niche can affect tissue homeostasis.

Hematopoietic progenitor cells as integrative hubs for adaptation to and fine-tuning of inflammation.

Recent advances have highlighted the ability of hematopoietic stem and progenitor cells in the bone marrow to sense peripheral inflammation or infection and adapt through increased proliferation and skewing toward the myeloid lineage. Such adaptations can meet the increased demand for innate immune cells and can be beneficial in response to infection or myeloablation. However, the inflammation-induced adaptation of hematopoietic and myeloid progenitor cells toward enhanced myelopoiesis might also perpetuate inflammation in chronic inflammatory or cardio-metabolic diseases by generating a feed-forward loop between inflammation-adapted hematopoietic progenitor cells and the inflammatory disorder. Sustained adaptive responses of progenitor cells in the bone marrow can also contribute to trained immunity, a non-specific memory of earlier encounters that in turn facilitates the heightened response of these cells, as well as that of their progeny, to future challenges. Here we discuss the mechanisms that govern the adaptation of hematopoietic progenitor cells to inflammation and its sequelae in the pathogenesis of human disease.

The evolution of fast-growing coral reef fishes.

Individual growth is a fundamental life history trait1-4, yet its macroevolutionary trajectories have rarely been investigated for entire animal assemblages. Here we analyse the evolution of growth in a highly diverse vertebrate assemblage-coral reef fishes. We combine state-of-the-art extreme gradient boosted regression trees with phylogenetic comparative methods to detect the timing, number, location and magnitude of shifts in the adaptive regime of somatic growth. We also explored the evolution of the allometric relationship between body size and growth. Our results show that the evolution of fast growth trajectories in reef fishes has been considerably more common than the evolution of slow growth trajectories. Many reef fish lineages shifted towards faster growth and smaller body size evolutionary optima in the Eocene (56-33.9 million years ago), pointing to a major expansion of life history strategies in this Epoch. Of all lineages examined, the small-bodied, high-turnover cryptobenthic fishes shifted most towards extremely high growth optima, even after accounting for body size allometry. These results suggest that the high global temperatures of the Eocene5 and subsequent habitat reconfigurations6 might have been critical for the rise and retention of the highly productive, high-turnover fish faunas that characterize modern coral reef ecosystems.

A super-assembly of Whi3 encodes memory of deceptive encounters by single cells during yeast courtship.

Cellular behavior is frequently influenced by the cell's history, indicating that single cells may memorize past events. We report that budding yeast permanently escape pheromone-induced cell-cycle arrest when experiencing a deceptive mating attempt, i.e., not reaching their putative partner within reasonable time. This acquired behavior depends on super-assembly and inactivation of the G1/S inhibitor Whi3, which liberates the G1 cyclin Cln3 from translational inhibition. Super-assembly of Whi3 is a slow response to pheromone, driven by polyQ and polyN domains, counteracted by Hsp70, and stable over generations. Unlike prion aggregates, Whi3 super-assemblies are not inherited mitotically but segregate to the mother cell. We propose that such polyQ- and polyN-based elements, termed here mnemons, act as cellular memory devices to encode previous environmental conditions.

Genomic insights into population history and biological adaptation in Oceania.

The Pacific region is of major importance for addressing questions regarding human dispersals, interactions with archaic hominins and natural selection processes1. However, the demographic and adaptive history of Oceanian populations remains largely uncharacterized. Here we report high-coverage genomes of 317 individuals from 20 populations from the Pacific region. We find that the ancestors of Papuan-related ('Near Oceanian') groups underwent a strong bottleneck before the settlement of the region, and separated around 20,000-40,000 years ago. We infer that the East Asian ancestors of Pacific populations may have diverged from Taiwanese Indigenous peoples before the Neolithic expansion, which is thought to have started from Taiwan around 5,000 years ago2-4. Additionally, this dispersal was not followed by an immediate, single admixture event with Near Oceanian populations, but involved recurrent episodes of genetic interactions. Our analyses reveal marked differences in the proportion and nature of Denisovan heritage among Pacific groups, suggesting that independent interbreeding with highly structured archaic populations occurred. Furthermore, whereas introgression of Neanderthal genetic information facilitated the adaptation of modern humans related to multiple phenotypes (for example, metabolism, pigmentation and neuronal development), Denisovan introgression was primarily beneficial for immune-related functions. Finally, we report evidence of selective sweeps and polygenic adaptation associated with pathogen exposure and lipid metabolism in the Pacific region, increasing our understanding of the mechanisms of biological adaptation to island environments.

Autophagy-Dependent Generation of Free Fatty Acids Is Critical for Normal Neutrophil Differentiation.

Neutrophils are critical and short-lived mediators of innate immunity that require constant replenishment. Their differentiation in the bone marrow requires extensive cytoplasmic and nuclear remodeling, but the processes governing these energy-consuming changes are unknown. While previous studies show that autophagy is required for differentiation of other blood cell lineages, its function during granulopoiesis has remained elusive. Here, we have shown that metabolism and autophagy are developmentally programmed and essential for neutrophil differentiation in vivo. Atg7-deficient neutrophil precursors had increased glycolytic activity but impaired mitochondrial respiration, decreased ATP production, and accumulated lipid droplets. Inhibiting autophagy-mediated lipid degradation or fatty acid oxidation alone was sufficient to cause defective differentiation, while administration of fatty acids or pyruvate for mitochondrial respiration rescued differentiation in autophagy-deficient neutrophil precursors. Together, we show that autophagy-mediated lipolysis provides free fatty acids to support a mitochondrial respiration pathway essential to neutrophil differentiation.

Phenotypic plasticity evolves at multiple biological levels in response to environmental predictability in a long-term experiment with a halotolerant microalga.

Phenotypic plasticity, the change in the phenotype of a given genotype in response to its environment of development, is a ubiquitous feature of life, enabling organisms to cope with variation in their environment. Theoretical studies predict that, under stationary environmental variation, the level of plasticity should evolve to match the predictability of selection at the timing of development. However, the extent to which patterns of evolution of plasticity for more integrated traits are mirrored by their underlying molecular mechanisms remains unclear, especially in response to well-characterized selective pressures exerted by environmental predictability. Here, we used experimental evolution with the microalgae Dunaliella salina under controlled environmental fluctuations, to test whether the evolution of phenotypic plasticity in responses to environmental predictability (as measured by the squared autocorrelation ρ2) occurred across biological levels, going from DNA methylation to gene expression to cell morphology. Transcriptomic analysis indicates clear effects of salinity and ρ2 × salinity interaction on gene expression, thus identifying sets of genes involved in plasticity and its evolution. These transcriptomic effects were independent of DNA methylation changes in cis. However, we did find ρ2-specific responses of DNA methylation to salinity change, albeit weaker than for gene expression. Overall, we found consistent evolution of reduced plasticity in less predictable environments for DNA methylation, gene expression, and cell morphology. Our results provide the first clear empirical signature of plasticity evolution at multiple levels in response to environmental predictability, and highlight the importance of experimental evolution to address predictions from evolutionary theory, as well as investigate the molecular basis of plasticity evolution.

Polygenic adaptation: a unifying framework to understand positive selection.

Most adaption processes have a polygenic genetic basis, but even with the recent explosive growth of genomic data we are still lacking a unified framework describing the dynamics of selected alleles. Building on recent theoretical and empirical work we introduce the concept of adaptive architecture, which extends the genetic architecture of an adaptive trait by factors influencing its adaptive potential and population genetic principles. Because adaptation can be typically achieved by many different combinations of adaptive alleles (redundancy), we describe how two characteristics - heterogeneity among loci and non-parallelism between replicated populations - are hallmarks for the characterization of polygenic adaptation in evolving populations. We discuss how this unified framework can be applied to natural and experimental populations.

Harnessing genomics to fast-track genetic improvement in aquaculture.

Aquaculture is the fastest-growing farmed food sector and will soon become the primary source of fish and shellfish for human diets. In contrast to crop and livestock production, aquaculture production is derived from numerous, exceptionally diverse species that are typically in the early stages of domestication. Genetic improvement of production traits via well-designed, managed breeding programmes has great potential to help meet the rising seafood demand driven by human population growth. Supported by continuous advances in sequencing and bioinformatics, genomics is increasingly being applied across the broad range of aquaculture species and at all stages of the domestication process to optimize selective breeding. In the future, combining genomic selection with biotechnological innovations, such as genome editing and surrogate broodstock technologies, may further expedite genetic improvement in aquaculture.

The genomics of coloration provides insights into adaptive evolution.

Coloration is an easily quantifiable visual trait that has proven to be a highly tractable system for genetic analysis and for studying adaptive evolution. The application of genomic approaches to evolutionary studies of coloration is providing new insight into the genetic architectures underlying colour traits, including the importance of large-effect mutations and supergenes, the role of development in shaping genetic variation and the origins of adaptive variation, which often involves adaptive introgression. Improved knowledge of the genetic basis of traits can facilitate field studies of natural selection and sexual selection, making it possible for strong selection and its influence on the genome to be demonstrated in wild populations.

Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition.

KRAS GTPases are activated in one-third of cancers, and KRAS(G12C) is one of the most common activating alterations in lung adenocarcinoma1,2. KRAS(G12C) inhibitors3,4 are in phase-I clinical trials and early data show partial responses in nearly half of patients with lung cancer. How cancer cells bypass inhibition to prevent maximal response to therapy is not understood. Because KRAS(G12C) cycles between an active and inactive conformation4-6, and the inhibitors bind only to the latter, we tested whether isogenic cell populations respond in a non-uniform manner by studying the effect of treatment at a single-cell resolution. Here we report that, shortly after treatment, some cancer cells are sequestered in a quiescent state with low KRAS activity, whereas others bypass this effect to resume proliferation. This rapid divergent response occurs because some quiescent cells produce new KRAS(G12C) in response to suppressed mitogen-activated protein kinase output. New KRAS(G12C) is maintained in its active, drug-insensitive state by epidermal growth factor receptor and aurora kinase signalling. Cells without these adaptive changes-or cells in which these changes are pharmacologically inhibited-remain sensitive to drug treatment, because new KRAS(G12C) is either not available or exists in its inactive, drug-sensitive state. The direct targeting of KRAS oncoproteins has been a longstanding objective in precision oncology. Our study uncovers a flexible non-uniform fitness mechanism that enables groups of cells within a population to rapidly bypass the effect of treatment. This adaptive process must be overcome if we are to achieve complete and durable responses in the clinic.

New insights into the troubles of aneuploidy.

Deviation from a balanced genome by either gain or loss of entire chromosomes is generally tolerated poorly in all eukaryotic systems studied to date. Errors in mitotic or meiotic cell division lead to aneuploidy, which places a burden of additional or insufficient gene products from the missegregated chromosomes on the daughter cells. The burden of aneuploidy often manifests itself as impaired fitness of individual cells and whole organisms, in which abnormal development is also characteristic. However, most human cancers, noted for their rapid growth, also display various levels of aneuploidy. Here we discuss the detrimental, potentially beneficial, and sometimes puzzling effects of aneuploidy on cellular and organismal fitness and tissue function as well as its role in diseases such as cancer and neurodegeneration.

Paths less traveled: evo-devo approaches to investigating animal morphological evolution.

One of the chief aims of modern biology is to understand the causes and mechanisms of morphological evolution. Multicellular animals display a stunning diversity of shapes and sizes of their bodies and individual suborganismal structures, much of it important to their survival. What is the most efficient way to study the evolution of morphological diversity? The old-new field of evolutionary developmental biology (evo-devo) can be particularly useful for understanding the origins of animal forms, as it aims to consolidate advances from disparate fields such as phylogenetics, genomics, morphometrics, cell biology, and developmental biology. We analyze the structure of some of the most successful recent evo-devo studies, which we see as having three distinct but highly interdependent components: (a) morphometrics, (b) identification of candidate mechanisms, and (c) functional experiments. Our case studies illustrate how multifarious evo-devo approaches taken within the three-winged evo-devo research program explain developmental mechanisms for morphological evolution across different phylogenetic scales.

Dynamic Phytomeric Growth Contributes to Local Adaptation in Barley.

Vascular plants have segmented body axes with iterative nodes and internodes. Appropriate node initiation and internode elongation are fundamental to plant fitness and crop yield; however, how these events are spatiotemporally coordinated remains elusive. We show that in barley (Hordeum vulgare L.), selections during domestication have extended the apical meristematic phase to promote node initiation, but constrained subsequent internode elongation. In both vegetative and reproductive phases, internode elongation displays a dynamic proximal-distal gradient, and among subpopulations of domesticated barleys worldwide, node initiation and proximal internode elongation are associated with latitudinal and longitudinal gradients, respectively. Genetic and functional analyses suggest that, in addition to their converging roles in node initiation, flowering-time genes have been repurposed to specify the timing and duration of internode elongation. Our study provides an integrated view of barley node initiation and internode elongation and suggests that plant architecture should be recognized as a collection of dynamic phytomeric units in the context of crop adaptive evolution.

The Chromosome-level Genome Provides Insights into the Evolution and Adaptation of Extreme Aggression.

Extremely aggressive behavior, as the special pattern, is rare in most species and characteristic as contestants severely injured or killed ending the combat. Current studies of extreme aggression are mainly from the perspectives of behavioral ecology and evolution, while lacked the aspects of molecular evolutionary biology. Here, a high-quality chromosome-level genome of the parasitoid Anastatus disparis was provided, in which the males exhibit extreme mate-competition aggression. The integrated multiomics analysis highlighted that neurotransmitter dopamine overexpression, energy metabolism (especially from lipid), and antibacterial activity are likely major aspects of evolutionary formation and adaptation for extreme aggression in A. disparis. Conclusively, our study provided new perspectives for molecular evolutionary studies of extreme aggression as well as a valuable genomic resource in Hymenoptera.

Non-Poissonian Bursts in the Arrival of Phenotypic Variation Can Strongly Affect the Dynamics of Adaptation.

Modeling the rate at which adaptive phenotypes appear in a population is a key to predicting evolutionary processes. Given random mutations, should this rate be modeled by a simple Poisson process, or is a more complex dynamics needed? Here we use analytic calculations and simulations of evolving populations on explicit genotype-phenotype maps to show that the introduction of novel phenotypes can be "bursty" or overdispersed. In other words, a novel phenotype either appears multiple times in quick succession or not at all for many generations. These bursts are fundamentally caused by statistical fluctuations and other structure in the map from genotypes to phenotypes. Their strength depends on population parameters, being highest for "monomorphic" populations with low mutation rates. They can also be enhanced by additional inhomogeneities in the mapping from genotypes to phenotypes. We mainly investigate the effect of bursts using the well-studied genotype-phenotype map for RNA secondary structure, but find similar behavior in a lattice protein model and in Richard Dawkins's biomorphs model of morphological development. Bursts can profoundly affect adaptive dynamics. Most notably, they imply that fitness differences play a smaller role in determining which phenotype fixes than would be the case for a Poisson process without bursts.

Rapid Adaptation and Interspecific Introgression in the North American Crop Pest Helicoverpa zea.

Insect crop pests threaten global food security. This threat is amplified through the spread of nonnative species and through adaptation of native pests to control measures. Adaptations such as pesticide resistance can result from selection on variation within a population, or through gene flow from another population. We investigate these processes in an economically important noctuid crop pest, Helicoverpa zea, which has evolved resistance to a wide range of pesticides. Its sister species Helicoverpa armigera, first detected as an invasive species in Brazil in 2013, introduced the pyrethroid-resistance gene CYP337B3 to South American H. zea via adaptive introgression. To understand whether this could contribute to pesticide resistance in North America, we sequenced 237 H. zea genomes across 10 sample sites. We report H. armigera introgression into the North American H. zea population. Two individuals sampled in Texas in 2019 carry H. armigera haplotypes in a 4 Mbp region containing CYP337B3. Next, we identify signatures of selection in the panmictic population of nonadmixed H. zea, identifying a selective sweep at a second cytochrome P450 gene: CYP333B3. We estimate that its derived allele conferred a ∼5% fitness advantage and show that this estimate explains independently observed rare nonsynonymous CYP333B3 mutations approaching fixation over a ∼20-year period. We also detect putative signatures of selection at a kinesin gene associated with Bt resistance. Overall, we document two mechanisms of rapid adaptation: the introduction of fitness-enhancing alleles through interspecific introgression, and selection on intraspecific variation.