Caspase-3/gasdermin-E axis facilitates the progression of coronary artery calcification by inducing the release of high mobility group box protein 1.

Coronary artery calcification (CAC) is commonly observed in atherosclerotic plaques, which is a pathogenic factor for severe coronary artery disease (CAD). The phenotype changes of vascular smooth muscle cells (VSMCs) are found to participate in CAC progression, which is mainly induced by vascular inflammation and oxidative stress (OS). HMGB1, a critical inflammatory cytokine, is recently reported to induce arterial calcification, which is regulated by the Caspase-3/gasdermin-E (GSDME) axis. However, the function of the Caspase-3/GSDME axis in CAC is unknown. Herein, the involvement of the Caspase-3/GSDME axis in CAC was studied to explore the possible targets for CAC. CAC model was constructed in mice, which was verified by red cytoplasm in coronary artery tissues, increased macrophage infiltration, aggravated inflammation, and enhanced RAGE signaling, accompanied by an increased release of HMGB1 and an activated Caspase-3/ GSDME axis. In ß-GP-treated MOVAS-1 cells, calcification, the ROS accumulation, enhanced LDH and HMGB1 release, enlarged macrophage production, aggravated inflammation, and activated RAGE signaling were observed, which were markedly abolished by the transfection of si-HMGB1 and si-GSDME. Moreover, the calcification deposition, the activity of Caspase-3/ GSDME axis, release of HMGB1, macrophage infiltration, cytokine production, and RAGE signaling in CAC mice were notably alleviated by VSMCs-specific GSDME knockdown, not by hematopoietic stem cells (HSCs)-specific GSDME knockdown. Collectively, Caspase-3/GSDME axis facilitated the progression of CAC by inducing the release of HMGB1.

Chromosome-level genomes of three key Allium crops and their trait evolution.

Allium crop breeding remains severely hindered due to the lack of high-quality reference genomes. Here we report high-quality chromosome-level genome assemblies for three key Allium crops (Welsh onion, garlic and onion), which are 11.17 Gb, 15.52 Gb and 15.78 Gb in size with the highest recorded contig N50 of 507.27 Mb, 109.82 Mb and 81.66 Mb, respectively. Beyond revealing the genome evolutionary process of Allium species, our pathogen infection experiments and comparative metabolomic and genomic analyses showed that genes encoding enzymes involved in the metabolic pathway of Allium-specific flavor compounds may have evolved from an ancient uncharacterized plant defense system widely existing in many plant lineages but extensively boosted in alliums. Using in situ hybridization and spatial RNA sequencing, we obtained an overview of cell-type categorization and gene expression changes associated with spongy mesophyll cell expansion during onion bulb formation, thus indicating the functional roles of bulb formation genes.

Ruminant-specific genes identified using high-quality genome data and their roles in rumen evolution.

Ruminants comprise a highly successful group of mammals with striking morphological innovations, including the presence of a rumen. Many studies have shown that species-specific or lineage-specific genes (referred to as new genes) play important roles in phenotypic evolution. In this study, we identified 1064 ruminant-specific genes based on the newly assembled high-quality genomes of representative members of two ruminant families and other publically available high-quality genomes. Ruminant-specific genes shared similar evolutionary and expression patterns with new genes found in other mammals, such as primates and rodents. Most new genes were derived from gene duplication and tended to be expressed in the testes or immune-related tissues, but were depleted in the adult brain. We also found that most genes expressed in the rumen were genes predating sheep-sperm whale split (referred to as old genes), but some new genes were also involved in the evolution of the rumen, and contributed more during rumen development than in the adult rumen. Notably, expression levels of members of the ruminant-specific PRD-SPRRII gene family, which are subject to positive selection, varied throughout rumen development and may thus play important roles in the development of the keratin-rich surface of the rumen. Overall, this study generated two novel ruminant genomes and also provided novel insights into the evolution of new mammalian organs.

Thirteen Dipterocarpoideae genomes provide insights into their evolution and borneol biosynthesis.

Dipterocarpoideae, the largest subfamily of the Dipterocarpaceae, is a dominant component of Southeast Asian rainforests and is widely used as a source of wood, damar resin, medicine, and essential oil. However, many Dipterocarpoideae species are currently on the IUCN Red List owing to severe degradation of their habitats under global climate change and human disturbance. Genetic information regarding these taxa has only recently been reported with the sequencing of four Dipterocarp genomes, providing clues to the function and evolution of these species. Here, we report on 13 high-quality Dipterocarpoideae genome assemblies, ranging in size from 302.6 to 494.8 Mb and representing the five most species-rich genera in Dipterocarpoideae. Molecular dating analyses support the Western Gondwanaland origin of Dipterocarpaceae. Based on evolutionary analysis, we propose a three-step chromosome evolution scenario to describe the karyotypic evolution from an ancestor with six chromosomes to present-day species with 11 and 7 chromosomes. We discovered an expansion of genes encoding cellulose synthase (CesA), which is essential for cellulose biosynthesis and secondary cell-wall formation. We functionally identified five bornyl diphosphate synthase (BPPS) genes, which specifically catalyze the biosynthesis of borneol, a natural medicinal compound extracted from damar resin and oils, thus providing a basis for large-scale production of natural borneol in vitro.

Comparative genome anatomy reveals evolutionary insights into a unique amphitriploid fish.

Triploids are rare in nature because of difficulties in meiotic and gametogenic processes, especially in vertebrates. The Carassius complex of cyprinid teleosts contains sexual tetraploid crucian carp/goldfish (C. auratus) and unisexual hexaploid gibel carp/Prussian carp (C. gibelio) lineages, providing a valuable model for studying the evolution and maintenance mechanism of unisexual polyploids in vertebrates. Here we sequence the genomes of the two species and assemble their haplotypes, which contain two subgenomes (A and B), to the chromosome level. Sequencing coverage analysis reveals that C. gibelio is an amphitriploid (AAABBB) with two triploid sets of chromosomes; each set is derived from a different ancestor. Resequencing data from different strains of C. gibelio show that unisexual reproduction has been maintained for over 0.82 million years. Comparative genomics show intensive expansion and alterations of meiotic cell cycle-related genes and an oocyte-specific histone variant. Cytological assays indicate that C. gibelio produces unreduced oocytes by an alternative ameiotic pathway; however, sporadic homologous recombination and a high rate of gene conversion also exist in C. gibelio. These genomic changes might have facilitated purging deleterious mutations and maintaining genome stability in this unisexual amphitriploid fish. Overall, the current results provide novel insights into the evolutionary mechanisms of the reproductive success in unisexual polyploid vertebrates.

Chromosome-level genome assembly of Welwitschia mirabilis, a unique Namib Desert species.

Welwitschia mirabilis, which is endemic to the Namib Desert, is the only living species within the family Welwitschiaceae. This species has an extremely long lifespan of up to 2,000 years and bears a single pair of opposite leaves that persist whilst alive. However, the underlying genetic mechanisms and evolution of the species remain poorly elucidated. Here, we report on a chromosome-level genome assembly for W. mirabilis, with a 6.30-Gb genome sequence and contig N50 of 27.50 Mb. In total, 39,019 protein-coding genes were predicted from the genome. Two brassinosteroid-related genes (BRI1 and CYCD3), key regulators of cell division and elongation, were strongly selected in W. mirabilis and may contribute to their long ever-growing leaves. Furthermore, 29 gene families in the mitogen-activated protein kinase signalling pathway showed significant expansion, which may contribute to the desert adaptations of the plant. Three positively selected genes (EHMT1, EIF4E, SOD2) may be involved in the mechanisms leading to long lifespan. Based on molecular clock dating and fossil calibrations, the divergence time of W. mirabilis and Gnetum montanum was estimated at ~123.5 million years ago. Reconstruction of population dynamics from genome data coincided well with the aridification of the Namib Desert. The genome sequence detailed in the current study provides insight into the evolution of W. mirabilis and should be an important resource for further study on gnetophyte and gymnosperm evolution.

Molecular mechanisms and topological consequences of drastic chromosomal rearrangements of muntjac deer.

Muntjac deer have experienced drastic karyotype changes during their speciation, making it an ideal model for studying mechanisms and functional consequences of mammalian chromosome evolution. Here we generated chromosome-level genomes for Hydropotes inermis (2n = 70), Muntiacus reevesi (2n = 46), female and male M. crinifrons (2n = 8/9) and a contig-level genome for M. gongshanensis (2n = 8/9). These high-quality genomes combined with Hi-C data allowed us to reveal the evolution of 3D chromatin architectures during mammalian chromosome evolution. We find that the chromosome fusion events of muntjac species did not alter the A/B compartment structure and topologically associated domains near the fusion sites, but new chromatin interactions were gradually established across the fusion sites. The recently borne neo-Y chromosome of M. crinifrons, which underwent male-specific inversions, has dramatically restructured chromatin compartments, recapitulating the early evolution of canonical mammalian Y chromosomes. We also reveal that a complex structure containing unique centromeric satellite, truncated telomeric and palindrome repeats might have mediated muntjacs' recurrent chromosome fusions. These results provide insights into the recurrent chromosome tandem fusion in muntjacs, early evolution of mammalian sex chromosomes, and reveal how chromosome rearrangements can reshape the 3D chromatin regulatory conformations during species evolution.

A towering genome: Experimentally validated adaptations to high blood pressure and extreme stature in the giraffe.

The suite of adaptations associated with the extreme stature of the giraffe has long interested biologists and physiologists. By generating a high-quality chromosome-level giraffe genome and a comprehensive comparison with other ruminant genomes, we identified a robust catalog of giraffe-specific mutations. These are primarily related to cardiovascular, bone growth, vision, hearing, and circadian functions. Among them, the giraffe FGFRL1 gene is an outlier with seven unique amino acid substitutions not found in any other ruminant. Gene-edited mice with the giraffe-type FGFRL1 show exceptional hypertension resistance and higher bone mineral density, both of which are tightly connected with giraffe adaptations to high stature. Our results facilitate a deeper understanding of the molecular mechanism underpinning distinct giraffe traits, and may provide insights into the study of hypertension in humans.