National Science Review

The origin and early evolution of lophotrochozoans remain a difficult but crucial issue in reconstructing metazoan phylogeny. Exceptionally preserved fossils have provided hopeful information for resolving this lophotrochozoan problem. Here we identify that Conicula striata, a soft-bodied conical animal from the early Cambrian Chengjiang Lagerstatte, has mosaic characteristics of different lophophorate phyla. C. striata possesses a phoronid-like vermiform trunk housing a U-shaped gut and a coiled lophophore comprising [≥]12 arms with numerous tentacles, but it also bears brachiopod-like features including an undivided mantle enclosing lophophore and a pedicle-like protrusion on annulated trunk. Phylogenetic analysis retrieves C. striata as a total-group lophophorate and as an intermediate taxon between Phoronida and Brachiopoda. This suggests that the bivalved architecture of brachiopods originated from an undivided mantle in a phoronid-like ancestor, and that the ancestral vermiform trunk became reduced during the origin of Brachiopoda, illuminating the origins of body plans in the lophophorate phyla.

The compacted macrofossil Protomelission? sp. from the early Cambrian Xiaoshiba Lagerstatte was recently ascribed to early dasycladalean green algae and used to disprove the bryozoan affinity of coeval phosphatized microfossils, which made the puzzling question whether the bryozoans originated in early Cambrian pending again. Our new analyses of multiple specimens which are conspecific with Protomelission? from the Chengjiang Lagerstatte indicate that they are not dasycladaleans but one of the three groups of archaeocyath-like sponges that atypically inhabited siliciclastic substrates. All the archaeocyath-like fossils share the same preservation mode and exhibit archaeocyath-type external skeletal features. Particularly, the Protomellision?-like fossils preserve structures indicative of archaeocyath aquiferous system and ontogeny. They represent the first recognized one-walled archaeocyath sponges in South China and evidence the niche expansion of archaeocyaths on their way of global radiation from Siberia, 518 million years ago. The origin of the bryozoans remains a mystery.

Before Cambrian Stage 3, unambiguous body fossils of segmented bilaterians were rare, severely hampering our understanding of the early history of such important animals. Here we report a variety of microfossils with quintessential features such as paired appendages, dorsoventral and anteroposterior differentiations from the basal Cambrian Fortunian of South China, representing the earliest known three-dimensional body fossils of segmented bilaterians. These fossils were all microbial pseudomorphs built up by secondarily phosphatized bacteria aggregations, testifying microbial pseudomorph could serve as a novel and important pathway to preserve tiny, fragile bilaterian progenitors. This finding unveils a diversified segmented bilaterian world at the very beginning of Cambrian and would arouse a more comprehensive perspective on the early evolution of bilaterian body plans.

The notable disparity of animal body plans can be traced back to the morphological innovations during the Cambrian explosion and represented by a number of exceptionally preserved soft-bodied and skeletal fossils that provide a compelling narrative for animal evolution. Chancelloriids, one of the extinct groups of Cambrian animals, have a distinctive body that characterized by a sclerite-bearing, flexible integument and a single apical opening leading into a central cavity devoid of unequivocal internal organs. Their phylogenetic position within the Metazoa, however, is controversial. Here, we describe new soft-bodied fossils of chancelloriids from the 518-million-year-old Chengjiang biota of China, which corroborate the unique bauplan pattern and reveal exquisite integument microstructures. The tiny protuberances and wrinkling structures of the integument are interpreted to be related to primitive epithelial contraction, suggesting that chancelloriids were a group of basal epitheliozoans and constitute an evolutionary clade that branched below all extant eumetazoans while above or close to the placozoans. Thus, the chancelloriid body plan likely filled one of the anatomical gaps between the Placozoa and the Eumetazoa.

Golden section is a subtle technology from nature to split space, which is both extensive and mysterious. In recent years, some studies1-4 have begun to focus on metabolic scaling (B{propto}Mb) at the macroevolutionary scale, and some important trends have been revealed. To further answer the question of "where does b come from and where does it go in evolution", a golden section model of macroevolution was constructed by integrating metabolic scaling and Fibonacci sequence. The results showed that, (1) macroevolution at the boundary level was a highly ordered process from one-dimensional (prokaryotes) to five-dimensional evolution (fungi). Four-dimensional life5 was only the choice of animals. (2) b just was the syndrome of dimension application and metabolism realization of life following Fibonacci sequence; however, it indicated major evolution events in the macroevolution and the directions in secondary macroevolution. The logic and panorama of macroevolution therefore were re-outlined based on the idea of dimensional evolution and metabolic evolution. It was argued that the golden section model of macroevolution established a full-new logic system of dimensional and metabolic evolution, and provided a possible path for the unification of macroevolution and microevolution.

Stegosaurs are a small but iconic clade of ornithischian dinosaurs. They and their sister taxa, the ankylosaurs, formed the clade Eurypoda which means broad-footed. Here, we describe a stegosaur from the Upper Jurassic Qigu Formation of Xinjiang, China, based on an associated partial skeleton that includes axial, pectoral girdle, pelvic girdle, limb and armor elements. It can be diagnosed as a new taxon, Angustungui, based on numerous autapomorphies. Some morphologies of Angustungui are more similar to the taxa from Europe, Africa and North America than to those from Asia. Our phylogenetic analysis recovers it as the sister taxon of Loricatosaurus. More importantly, the narrow and claw-shaped ungual of Angustungui proves that Eurypoda, at least stegosaur, has claw-shaped unguals. Besides, we revised the character scores for Chinese stegosaurs based on observations of the specimens.

The genus Macaca, with 23 species assigned into four to seven species groups, exhibits the largest geographic range and represents the most successful adaptive radiation of nonhuman primates. Here, we conducted phylogenomic analyses of 16 newly generated and eight published macaque genomes and found a strong support for the division of this genus into seven species groups. Both ancient hybrid and incomplete lineage sorting (ILS) have contributed to the radiation and evolution of macaques. Particularly, the contradicting phylogenetic positions among silenus/nigra, fascicularis/mulatta and arctoides/sinica lineages were likely resulted from high level of ILS and potential hybridization between the ancestors of the arctoides/sinica and silenus/nigra lineages. Furthermore, an integrated scenario for macaque radiation is reconstructed by the help of the dated phylogenetic tree combined with documented history records. This study provides insights into ancient introgression involved in the radiation of macaques, which may help us to understand the rapid speciation of nonhuman primates.

Yeast, a single eukaryotic cell model organism, demonstrates a progressive aging process. In the era of synthetic biology, study of the impact of synthetic chromosomes and aging is urgent and intriguing. Herein, we successfully constructed the 884 Kb synXIII of Saccharomyces cerevisiae and conducted replicative aging studies using the synthetic strains. We verified that the rRNA-related transcriptional factor RRN9 is a major positive controller of replicative lifespan. Using SCRaMbLE and an HSP104 reporter as a biomarker for mutant discovery, we screened 135 SCRaMbLEd synXIII strains with extended lifespan and identified 10 genes on synXIII that potentially serve as aging regulators. In addition, the genome-scale regression analysis of long-replicative lifespan SCRaMbLEd strains revealed distinct dysregulation of nucleus, ribosome, and mitochondrion function networks. Our findings suggest that Sc2.0 yeast has potential for unveiling new aging-related genes and gene-gene interactions underlying replicative lifespan.

As a novel molecular evolution model that was claimed to have an advantage over the molecular clock hypothesis1-3, the maximum genetic diversity (MGD) hypothesis was utilized to study the modern human origins4. Nevertheless, there are serious problems with this hypothesis and both it and its derivative studies should be treated with caution.

Discrimination for sound frequency is essential for auditory communications in animals. Here, by combining in vivo calcium imaging and behavioral assay, we found that Drosophila larvae can sense a wide range of sound frequency and the behavioral specificity is mediated with the selectivity of the lch5 chordotonal organ neurons to sounds that forms a combinatorial coding of frequency. We also disclosed that Brivido1 (Brv1) and Piezo-like (Pzl), each expresses in a subset of lch5 neurons and mediate hearing sensation to certain frequency ranges. Intriguingly, mouse Piezo2 can rescue pzl-mutants phenotypes, suggesting a conserved role of the Piezo family proteins in high-frequency hearing.

The first 10 million years (Myr) following the Cretaceous-Paleogene (K-Pg) mass extinction marked a period of global greenhouse conditions and dramatic rise of placental mammals. Because [~]80% of known terrestrial sections capturing post-K-Pg mammal recovery come from North America, a substantial knowledge gap exists in the tempo and mode of recovery in Asia, where only 3% of sites are located and most contain species found nowhere else. We show that isolated Paleocene placental assemblages from China (1) reached high tooth size disparity early in the Paleocene, (2) tracked regional and global environmental changes in their dental shape later in the Paleocene, and (3) achieved maximum dental shape-performance integration near the end of the first 10 Myr post-K-Pg. This brawn before bite transformation, coupled with prolonged dental shape versus performance variability, favors a scenario whereby many living orders of placental mammals were borne out of phenotypically and functionally plastic ancestral assemblages, including those in tropical south China, during the Paleocene.

The greatest mass extinction at the end of the Permian, ca. 252 million years ago, led to a tropical dead zone on land and sea. The speed of recovery of life has been debated, whether fast or slow, and terrestrial ecosystems are much less understood than marine. Here, we show fast reestablishment of riparian ecosystems in low-latitude North China as little as [~]2 million years after the end-Permian mass extinction. The initial ichnoassemblages in shallow lacustrine and fluvial facies of late Smithian age are monospecific, devoid of infaunalization, with apparent size reduction. In the following Spathian, relatively complex, multi-level, structured riverain ecosystems had been rebuilt including medium-sized carnivores, plant stems, root traces, increased ichnological complexity, and significantly increased infaunalization. Specifically, burrowing behavior had re-emerged as a key life strategy not only to minimize stressful climatic conditions, but possibly to escape predation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause the most serious pandemics of Coronavirus Disease 2019 (COVID-19), which threatens human health and public safety. SARS-CoV-2 spike (S) protein uses angiotensin-converting enzyme 2 (ACE2) as recognized receptor for its entry into host cell that contributes to the infection of SARS-CoV-2 to hosts. Using computational modeling approach, this study resolved the evolutionary pattern of bonding affinity of ACE2 in 247 jawed vertebrates to the spike (S) protein of SARS-CoV-2. First, high-or-low binding affinity phenotype divergence of ACE2 to the S protein of SARS-CoV-2 has appeared in two ancient species of jawed vertebrates, Scyliorhinus torazame (low-affinity, Chondrichthyes) and Latimeria chalumnae (high-affinity, Coelacanthimorpha). Second, multiple independent affinity divergence events recur in fishes, amphibians-reptiles, birds, and mammals. Third, high affinity phenotypes go up in mammals, possibly implying the rapid expansion of mammals might accelerate the evolution of coronaviruses. Fourth, we found natural mutations at eight amino acid sites of ACE2 can determine most of phenotype divergences of bonding affinity in 247 vertebrates and resolved their related structural basis. Moreover, we also identified high-affinity or low-affinity-associated concomitant mutation group.The group linked to extremely high affinity may provide novel potentials for the development of human recombinant soluble ACE2 (hrsACE2) in treating patients with COVID-19 or for constructing genetically modified SARS-CoV-2 infection models promoting vaccines studies. These findings would offer potential benefits for the treatment and prevention of SARS-CoV-2.

Understanding the differences between genomic sequences of different lives is crucial for biological classification and phylogeny. Here, we downloaded all the reliable sequences of the seven kingdoms and determined the dimensions of the genome space embedded in the Euclidean space, along with the corresponding Natural Metrics. The concept of the Grand Biological Universe is further proposed. In the grand universe, the convex hulls formed by the universes of seven kingdoms are mutually disjoint, and the convex hulls formed by different biological groups within each kingdom are mutually disjoint. This study provides a novel geometric perspective for studying molecular biology and also offers an accurate way for large-scale sequence comparison in a real-time manner. Most importantly, this study shows that, due to the space-time distortion in the biological genome space similar to Einsteins theory, it is futile to look for a single metric to measure different biological universes, as previous studies have done.

Nanhsiungchelyidae are a group of large turtles that lived in Asia and North America during the Cretaceous. Here we report a new species of nanhsiungchelyid, Nanhsiungchelys yangi sp. nov., from the Upper Cretaceous of Nanxiong Basin, China. This is the second valid species of Nanhsiungchelys, and the holotype consists of a well-preserved skull and lower jaw, as well as the anterior parts of the carapace and plastron. The diagnostic features of Nanhsiungchelys include a huge estimated body size (~55.5 cm), a special network of sculptures on the surface of the skull and shell, weak cheek emargination and temporal emargination, deep nuchal emargination, and a pair of anterolateral processes on the carapace. However, Nanhsiungchelys yangi differs from the other species of Nanhsiungchelys in having a triangular-shaped snout and wide anterolateral processes. A phylogenetic analysis of nanhsiungchelyids places Nanhsiungchelys yangi and Nanhsiungchelys wuchingensis as sister taxa. Some nanhsiungchelyids bear special anterolateral processes on the carapace, which are unknown in extant turtles. Here we test the function of these processes in Nanhsiungchelys yangi using computational fluid dynamics, and the results suggest these processes could enhance locomotory performance by remarkably reducing drag force when the animal was swimming through water.

Cancer cachexia is one of the most common causes of death among cancer patients, no effective anti-cachectic treatment is currently available. In experimental cachectic models, aberrant activation of STAT3 in skeletal muscle has been found to contribute to muscle wasting. However, its clinical association, the factors regulating STAT3 activation, and the molecular mechanisms of STAT3-induced muscle atrophy in cancer cachexia remain incompletely understood. Here, we show that an enhanced interaction between STAT3 and HSP90, which causes the persistent STAT3 activation in the skeletal muscle of cancer cachexia patients, is the crucial event for the development of cachectic muscle wasting. Administration of HSP90 inhibitors alleviated the muscle wasting in C26 tumor-bearing cachetic mice model or C26 conditional medium induced C2C12 myotube atrophy. A mechanistic study indicated that in cachectic skeletal muscle, prolonged STAT3 activation triggered muscle wasting in a FOXO1-dependent manner, STAT3 activated FOXO1 by binding directly to its promoter. Our results provide key insights into the role of the HSP90/STAT3/FOXO1 axis in cachectic muscle wasting, which shows promising therapeutic potential as a target for the treatment of cancer cachexia.

Amphioxus is considered the best-known living proxy to the chordate ancestor and an irreplaceable model organism for evolutionary studies of chordates and deuterostomes. In this study, a high-quality genome of the Beihai amphioxus, Branchiostoma belcheri beihai, was de novo assembled and annotated. Within four amphioxus genomes, twenty-eight groups of gene novelties were identified, revealing new genes that lack homologs in non-deuterostome metazoa, but share unexpectedly high similarities with those from non-metazoan species. These gene innovation events have played roles in amphioxus adaptations, including innate immunity responses, glycolysis, and regulation of calcium balance. The gene novelties related to innate immunity, such as a group of lipoxygenases and a DEAD-box helicase, boosted amphioxus immune responses. The novel genes for alcohol dehydrogenase and ferredoxin could aid in the glycolysis of amphioxus. A proximally arrayed cluster of EF-hand calcium-binding protein genes were identified to resemble those of bacteria. The copy number of this gene cluster was negatively correlated to the sea salinity of the collection region, suggesting that it may enhance their survival at different calcium concentrations. This comprehensive study collectively reveals insights into adaptive evolution of cephalochordates and provides valuable resources for research on early evolution of deuterostomes.

Obese subjects often exhibit hypersomnia accompanied by severe sleep fragmentation, while emerging evidence suggests that poor sleep quality promotes overeating and exacerbates diet-induced obesity (DIO). However, the neural circuit and signaling mechanism underlying the reciprocal control of appetite and sleep is yet not elucidated. Here, we report a neural circuit where prokineticin receptor 2 (PROKR2)-expressing neurons within the parabrachial nucleus (PBN) of the brainstem received direct projections from neuropeptide Y receptor Y2 (NPY2R)-expressing neurons within the lateral preoptic area (LPO) of the hypothalamus. The RNA-Seq results revealed Prokr2 in the PBN is the most regulated GPCR signaling gene that is responsible for comorbidity of obesity and sleep dysfunction. Furthermore, those NPY2RLPO neurons are minimally active during NREM sleep and maximally active during wakefulness and REM sleep. Activation of the NPY2RLPO[->]PBN circuit or the postsynaptic PROKR2PBN neurons suppressed feeding of a high-fat diet and abrogated morbid sleep patterns in DIO mice. Further studies showed that genetic ablation of the PROKR2 signaling within PROKR2PBN neurons alleviated the hyperphagia and weight gain, and restored sleep dysfunction in DIO mice. We further discovered pterostilbene, a plant-derived stilbenoid, is a powerful anti-obesity and sleep-improving agent, robustly suppressed hyperphagia and promoted reconstruction of a healthier sleep architecture, thereby leading to significant weight loss. Collectively, our results unveil a neural mechanism for the reciprocal control of appetite and sleep, through which pterostilbene, along with a class of similarly structured compounds, may be developed as effective therapeutics for tackling obesity and sleep disorders.

Humans and animals are not always rational. They not only rationally exploit rewards but also explore an environment, even if reward is less expected, owing to their curiosity. However, the mechanism of such curiosity-driven irrational behavior is largely unknown. Here, we developed a novel decision-making model for a two-choice task based on the free energy principle, which is a theory integrating recognition and action selection. The model successfully described irrational behaviors depending on the curiosity level. We then proposed a machine learning method to decode temporal curiosity from behavioral data, which enables us to quantitatively compare estimated curiosity and neural activities. By applying it to rat behavioral data, we found that the irrational choices sticking to one option was reflected to the negative curiosity level. Our decoding approach can be a fundamental tool for identifying the neural basis for reward-curiosity conflicts. Specifically, it could be effective in diagnosing mental disorders.

Understanding loss-of-function mutations and their potential compensatory mechanisms is crucial for elucidating the complexities of gene expression. Here, we investigate whether additional mutations can rescue non-functional alleles and their evolutionary significance. To achieve this, we conducted an extensive analysis of 372,867 amino acid sequence variants of the imidazole glycerol-phosphate dehydratase (IGPD, PDB: 6ezm) protein, which is over 1000 times greater than previously examined. We discovered that one or more additional substitutions located in loop and interface regions could easily restore function for each of the 10,019 of 31,701 (31.6%) non-functional missense allele. We further identified a small set of super-compensatory substitutions that can increase the function of many diverse alleles and flatten the fitness landscape, that is, buffer the fitness effects of both beneficial and deleterious substitutions. We also found that the protein structures of rescuable variants are more stable than those of non-rescuable variants. This suggests that restoring the stability of protein structures is a key part of compensation. These findings offer new insights into the understanding of protein function loss and its adaptive compensatory evolution.