There is another: H3K27me3-mediated genomic imprinting.

DNA methylation has long been considered the primary epigenetic mediator of genomic imprinting in mammals. Recent epigenetic profiling during early mouse development revealed the presence of domains of trimethylation of lysine 27 on histone H3 (H3K27me3) and chromatin compaction specifically at the maternally derived allele, independent of DNA methylation. Within these domains, genes are exclusively expressed from the paternally derived allele. This novel mechanism of noncanonical imprinting plays a key role in the development of mouse extraembryonic tissues and in the regulation of imprinted X-chromosome inactivation, highlighting the importance of parentally inherited epigenetic histone modifications. Here, we discuss the mechanisms underlying H3K27me3-mediated noncanonical imprinting in perspective of the dynamic chromatin landscape during early mouse development and explore evolutionary origins of noncanonical imprinting.

Evolutionary origin of germline pathogenic variants in human DNA mismatch repair genes.

BACKGROUND: Mismatch repair (MMR) system is evolutionarily conserved for genome stability maintenance. Germline pathogenic variants (PVs) in MMR genes that lead to MMR functional deficiency are associated with high cancer risk. Knowing the evolutionary origin of germline PVs in human MMR genes will facilitate understanding the biological base of MMR deficiency in cancer. However, systematic knowledge is lacking to address the issue. In this study, we performed a comprehensive analysis to know the evolutionary origin of human MMR PVs. METHODS: We retrieved MMR gene variants from the ClinVar database. The genomes of 100 vertebrates were collected from the UCSC genome browser and ancient human sequencing data were obtained through comprehensive data mining. Cross-species conservation analysis was performed based on the phylogenetic relationship among 100 vertebrates. Rescaled ancient sequencing data were used to perform variant calling for archeological analysis. RESULTS: Using the phylogenetic approach, we traced the 3369 MMR PVs identified in modern humans in 99 non-human vertebrate genomes but found no evidence for cross-species conservation as the source for human MMR PVs. Using the archeological approach, we searched the human MMR PVs in over 5000 ancient human genomes dated from 45,045 to 100 years before present and identified a group of MMR PVs shared between modern and ancient humans mostly within 10,000 years with similar quantitative patterns. CONCLUSION: Our study reveals that MMR PVs in modern humans were arisen within the recent human evolutionary history.

Evolutionary origin and gradual accumulation with plant evolution of the LACS family.

BACKGROUND: LACS (long-chain acyl-CoA synthetase) genes are widespread in organisms and have multiple functions in plants, especially in lipid metabolism. However, the origin and evolutionary dynamics of the LACS gene family remain largely unknown. RESULTS: Here, we identified 1785 LACS genes in the genomes of 166 diverse plant species and identified the clades (I, II, III, IV, V, VI) of six clades for the LACS gene family of green plants through phylogenetic analysis. Based on the evolutionary history of plant lineages, we found differences in the origins of different clades, with Clade IV originating from chlorophytes and representing the origin of LACS genes in green plants. The structural characteristics of different clades indicate that clade IV is relatively independent, while the relationships between clades (I, II, III) and clades (V, VI) are closer. Dispersed duplication (DSD) and transposed duplication (TRD) are the main forces driving the evolution of plant LACS genes. Network clustering analysis further grouped all LACS genes into six main clusters, with genes within each cluster showing significant co-linearity. Ka/Ks results suggest that LACS family genes underwent purifying selection during evolution. We analyzed the phylogenetic relationships and characteristics of six clades of the LACS gene family to explain the origin, evolutionary history, and phylogenetic relationships of different clades and proposed a hypothetical evolutionary model for the LACS family of genes in plants. CONCLUSIONS: Our research provides genome-wide insights into the evolutionary history of the LACS gene family in green plants. These insights lay an important foundation for comprehensive functional characterization in future research.

Pathogenic variants in human DNA damage repair genes mostly arose in recent human history.

BACKGROUND: Genome stability is maintained by the DNA damage repair (DDR) system composed of multiple DNA repair pathways of hundreds of genes. Germline pathogenic variation (PV) in DDR genes damages function of the affected DDR genes, leading to genome instability and high risk of diseases, in particular, cancer. Knowing evolutionary origin of the PVs in human DDR genes is essential to understand the etiology of human diseases. However, answer to the issue remains largely elusive. In this study, we analyzed evolutionary origin for the PVs in human DDR genes. METHODS: We identified 169 DDR genes by referring to various databases and identified PVs in the DDR genes of modern humans from ClinVar database. We performed a phylogenetic analysis to analyze the conservation of human DDR PVs in 100 vertebrates through cross-species genomic data comparison using the phyloFit program of the PHAST package and visualized the results using the GraphPad Prism software and the ggplot module. We identified DDR PVs from over 5000 ancient humans developed a database to host the DDR PVs ( https://genemutation.fhs.um.edu.mo/dbDDR-AncientHumans ). Using the PV data, we performed a molecular archeological analysis to compare the DDR PVs between modern humans and ancient humans. We analyzed evolution selection of DDR genes across 20 vertebrates using the CodeML in PAML for phylogenetic analysis. RESULTS: Our phylogenic analysis ruled out cross-species conservation as the origin of human DDR PVs. Our archeological approach identified rich DDR PVs shared between modern and ancient humans, which were mostly dated within the last 5000 years. We also observed similar pattern of quantitative PV distribution between modern and ancient humans. We further detected a set of ATM, BRCA2 and CHEK2 PVs shared between human and Neanderthals. CONCLUSIONS: Our study reveals that human DDR PVs mostly arose in recent human history. We propose that human high cancer risk caused by DDR PVs can be a by-product of human evolution.

Evolutionary Origin of Human PALB2 Germline Pathogenic Variants.

PALB2 (Partner and localizer of BRCA2) is crucial for repairing DNA double-stranded breaks (DSBs) through homologous recombination (HR). Germline pathogenic variation in PALB2 disrupts DNA damage repair and increases the risk of Fanconi Anemia, breast cancer, and ovarian cancer. Determination of the evolutionary origin of human PALB2 variants will promote a deeper understanding of the biological basis of PALB2 germline variation and its roles in human diseases. We tested the evolution origin for 1444 human PALB2 germline variants, including 484 pathogenic and 960 benign variants. We performed a phylogenic analysis by tracing the variants in 100 vertebrates. However, we found no evidence to show that cross-species conservation was the origin of PALB2 germline pathogenic variants, but it is indeed a rich source for PALB2 germline benign variants. We performed a paleoanthropological analysis by tracing the variants in over 5000 ancient humans. We identified 50 pathogenic in 71 ancient humans dated from 32,895 to 689 before the present, of which 90.1% were dated within the recent 10,000 years. PALB2 benign variants were also highly shared with ancient humans. Data from our study reveal that human PALB2 pathogenic variants mostly arose in recent human history.

Multi-omics analysis reveals the evolutionary origin of diterpenoid alkaloid biosynthesis pathways in Aconitum.

Diterpenoid alkaloids (DAs) have been often utilized in clinical practice due to their analgesic and anti-inflammatory properties. Natural DAs are prevalent in the family Ranunculaceae, notably in the Aconitum genus. Nevertheless, the evolutionary origin of the biosynthesis pathway responsible for DA production remains unknown. In this study, we successfully assembled a high-quality, pseudochromosome-level genome of the DA-rich species Aconitum vilmorinianum (A. vilmorinianum) (5.76 Gb). An A. vilmorinianum-specific whole-genome duplication event was discovered using comparative genomic analysis, which may aid in the evolution of the DA biosynthesis pathway. We identified several genes involved in DA biosynthesis via integrated genomic, transcriptomic, and metabolomic analyses. These genes included enzymes encoding target ent-kaurene oxidases and aminotransferases, which facilitated the activation of diterpenes and insertion of nitrogen atoms into diterpene skeletons, thereby mediating the transformation of diterpenes into DAs. The divergence periods of these genes in A. vilmorinianum were further assessed, and it was shown that two major types of genes were involved in the establishment of the DA biosynthesis pathway. Our integrated analysis offers fresh insights into the evolutionary origin of DAs in A. vilmorinianum as well as suggestions for engineering the biosynthetic pathways to obtain desired DAs.

Progress on the mechanism of left-right asymmetrical patterning in bilaterians.

Left-right asymmetry is an essential feature in bilateral animals. The mechanism underlying the left-right asymmetrical organ morphogenesis is a central question in developmental biology. Studies in vertebrates show that left-right asymmetry formation needs three essential steps: the initial left-right symmetry breaking, the left-right asymmetrical gene expression, and the left-right asymmetrical organ morphogenesis. Many vertebrates use cilia to produce directional fluid flow to break symmetry during embryonic development, asymmetric Nodal-Pitx2 signaling to pattern the left-right asymmetry, and Pitx2 and other genes to control the morphogenesis of asymmetrical organs. In invertebrates, there are left-right mechanisms independent of cilia and even others more different from that of vertebrates. In this review, we summarize the major steps and relevant molecular mechanisms of left-right asymmetric development in vertebrates and invertebrates, aiming to provide a reference for the understanding of the origin and evolution of the left-right developmental mechanism.

Evolutionary history of Plasmodium vivax and Plasmodium simium in the Americas.

Malaria is a vector-borne disease caused by protozoan parasites of the genus Plasmodium. Plasmodium vivax is the most prevalent human-infecting species in the Americas. However, the origins of this parasite in this continent are still debated. Similarly, it is now accepted that the existence of Plasmodium simium is explained by a P. vivax transfer from humans to monkey in America. However, many uncertainties still exist concerning the origin of the transfer and whether several transfers occurred. In this review, the most recent studies that addressed these questions using genetic and genomic approaches are presented.

Jasmonate Signaling Pathway Modulates Plant Defense, Growth, and Their Trade-Offs.

Lipid-derived jasmonates (JAs) play a crucial role in a variety of plant development and defense mechanisms. In recent years, significant progress has been made toward understanding the JA signaling pathway. In this review, we discuss JA biosynthesis, as well as its core signaling pathway, termination mechanisms, and the evolutionary origin of JA signaling. JA regulates not only plant regeneration, reproductive growth, and vegetative growth but also the responses of plants to stresses, including pathogen as well as virus infection, herbivore attack, and abiotic stresses. We also focus on the JA signaling pathway, considering its crosstalk with the gibberellin (GA), auxin, and phytochrome signaling pathways for mediation of the trade-offs between growth and defense. In summary, JA signals regulate multiple outputs of plant defense and growth and act to balance growth and defense in order to adapt to complex environments.

Tergal and pleural wing-related tissues in the German cockroach and their implication to the evolutionary origin of insect wings.

The acquisition of wings has facilitated the massive evolutionary success of pterygotes (winged insects), which now make up nearly three-quarters of described metazoans. However, our understanding of how this crucial structure has evolved remains quite elusive. Historically, two ideas have dominated in the wing origin debate, one placing the origin in the dorsal body wall (tergum) and the other in the lateral pleural plates and the branching structures associated with these plates. Through studying wing-related tissues in the wingless segments (such as wing serial homologs) of the beetle, Tribolium castaneum, we obtained several crucial pieces of evidence that support a third idea, the dual origin hypothesis, which proposes that wings evolved from a combination of tergal and pleural tissues. Here, we extended our analysis outside of the beetle lineage and sought to identify wing-related tissues from the wingless segments of the cockroach, Blattella germanica. Through detailed functional and expression analyses for a critical wing gene, vestigial (vg), along with re-evaluating the homeotic transformation of a wingless segment induced by an improved RNA interference protocol, we demonstrate that B. germanica possesses two distinct tissues in their wingless segments, one with tergal and one with pleural nature, that might be evolutionarily related to wings. This outcome appears to parallel the reports from other insects, which may further support a dual origin of insect wings. However, we also identified a vg-independent tissue that contributes to wing formation upon homeotic transformation, as well as vg-dependent tissues that do not appear to participate in wing formation, in B. germanica, indicating a more complex evolutionary history of the tissues that contributed to the emergence of insect wings.

Discovery of Hyperactive Antifreeze Protein from Phylogenetically Distant Beetles Questions Its Evolutionary Origin.

Beetle hyperactive antifreeze protein (AFP) has a unique ability to maintain a supercooling state of its body fluids, however, less is known about its origination. Here, we found that a popular stag beetle Dorcus hopei binodulosus (Dhb) synthesizes at least 6 isoforms of hyperactive AFP (DhbAFP). Cold-acclimated Dhb larvae tolerated -5 °C chilled storage for 24 h and fully recovered after warming, suggesting that DhbAFP facilitates overwintering of this beetle. A DhbAFP isoform (~10 kDa) appeared to consist of 6-8 tandem repeats of a 12-residue consensus sequence (TCTxSxNCxxAx), which exhibited 3 °C of high freezing point depression and the ability of binding to an entire surface of a single ice crystal. Significantly, these properties as well as DNA sequences including the untranslated region, signal peptide region, and an AFP-encoding region of Dhb are highly similar to those identified for a known hyperactive AFP (TmAFP) from the beetle Tenebrio molitor (Tm). Progenitor of Dhb and Tm was branched off approximately 300 million years ago, so no known evolution mechanism hardly explains the retainment of the DNA sequence for such a lo-ng divergence period. Existence of unrevealed gene transfer mechanism will be hypothesized between these two phylogenetically distant beetles to acquire this type of hyperactive AFP.

Freshwater entry behaviour of a non-migratory stenohaline marine fish Takifugu snyderi.

We conducted salinity choice trials with the stenohaline marine species Takifugu snyderi to test their freshwater (FW) entry frequency in relation to starvation. The fish preferred to enter non-natal FW rather than remain in seawater. No relationship was detected between starvation and FW entry behaviour. Our results provide new empirical evidence of a stenohaline fish entering a non-natal osmotic environment. Further research on the entry of stenohaline species such as this one into lethal environments may help determine if this might help promote the evolution of diadromous life histories.

A new biological species in the Mercurialis annua polyploid complex: functional divergence in inflorescence morphology and hybrid sterility.

BACKGROUND AND AIMS: Polyploidy has played a major role in the origin of new plant species, probably because of the expansion of polyploid populations in the species' ecological niche, and because reproductive isolation can be established between a new polyploid population and its diploid progenitor species. It is well established that most polyploid species are polyphyletic, with multiple independent origins, and that polyploid genomes may undergo rapid change after their duplication and hybridization associated with their origin. We considered whether multiple independent origins and rapid genomic change might lead to reproductive isolation between polyploid populations of the same ploidy but with potentially different evolutionary histories. METHODS: We tested our hypothesis by assessing differences in DNA content and morphology, the evolution of reproductive isolation, and the phylogenetic placement of two broadly sympatric hexaploid lineages of the wind-pollinated annual plant Mercurialis annua hitherto regarded as populations of the same species. KEY RESULTS: The two hexaploid lineages of M. annua have slightly divergent DNA content, and distinct inflorescence morphology. They also fall into largely different clades of a chloroplast phylogeny and are reproductively isolated from one another. CONCLUSIONS: The distinct evolutionary histories of the two hexaploid lineages of M. annua have contributed to the remarkable reproductive diversity of the species complex. It seems likely that reproductive interference between them will eventually lead to the displacement of one lineage by the other via pollen swamping. Thus, whereas polyploidization can contribute to speciation, diversification might also be compromised by reproductive interference.

Developmental pathways of periodontal tissue regeneration: Developmental diversities of tooth morphogenesis do also map capacity of periodontal tissue regeneration?

Nothing is known on the impact of developmental divergence on periodontal tissue regeneration in vertebrate animals. Molecularly, the induction of tooth morphogenesis is highly conserved deploying across animal phyla a constant and reproducible set of gene pathways, which result in morphogenesis of multiple odontode forms and shapes. Genetic mutations positively affect animal speciation via evolving biting and masticatory forces as well as dietary habits selectively imprinted in animal phyla during evolutionary speciation. The geometry of the attachment apparatus of a tooth is important for the interpretation of the induction of cementogenesis with de novo Sharpey's fibres as in thecodonty, ie, a tripartite attachment of alveolar bone, periodontal ligament and cementum. This review addresses the tooth implantation in different animal clades from the fibrous attachment of the Elasmobranch Carcharinus obscurus dusky shark, reviewing the evolution and functional significance of cementum with functionally inserted Sharpey's fibres. In sharks there is a continuous tooth replacement mechanistically supported by the continuously erupting dental lamina. We show that the arching of the continuously erupting dental lamina, a critical step for the selachians' tooth differentiation, is prominently characterized by transforming growth factor-ß3 (TGF-ß3 ) expression not only within the dental lamina but also in cellular condensations in the mesenchymal tissues of the erupting tooth. Such findings indicate the pleiotropic multifaceted activity of a highly conserved mammalian gene across genera, masterminding tooth morphogenesis in both selachians and mammals as well as periodontal tissue induction in the non-human primate Papio ursinus. In P. ursinus, the induction of cementogenesis entails the expression of TGF-ß3 and osteocalcin with fine-tuning and regulation of bone morphogenetic proteins BMP-2 and BMP-7, and upregulation of TGF-ß3 . TGF-ß3 autoinduction and upregulation during the induction of cementogenesis and osteogenesis in P. ursinus provide novel insights into the induction of cementogenesis. It is hypothesized that the evolutionary expression and upregulation of the TGF-ß3 gene may provide the mechanistic insights into the induction of extensive cementogenesis as seen in stem mammals and the induction of trabecular-like cementum formation in mosasaurs' tooth attachment. Aspidin, the precursor of cementum, was reported to appear 310-330 million years ago (Ma) in Odontostraci armoured fish. Studies showed that the differentiation of cementum with inserted Sharpey's fibres is also present in lower amniotes such as Diatectomorpha or Diadectidae, the first herbivorous tetrapods, 323 Ma. In mosasaurs, 168-165 Ma, there is the induction of extensive trabeculation of cementum though nothing is known on the phylogenetic temporo-spatial evolution of cementum before Diadectidae and stem mammals. The large trabeculations of cementum as seen in the attachment of extinct mosasaurs invocates a pleiotropic capacity of cemental growth previously unknown. The appearance of cementum facing a vascularized and innervated periodontal ligament space with Sharpey's fibres inserting on to mineralized cementum provides a multiform pleiotropic masticatory apparatus adapted to multiple biting and lacerating forces as well as finely tuned and controlled forces beyond mastication and deglutition. The remarkable cementogenesis as seen in stem mammals but particularly in mosasaurs with cemental trabeculations across the ligament space invocates the developmental capacity of cementum. The large cemental trabeculations as seen in mosasaurs and the cemental growth in stem mammals, together with regenerating scenarios in P. ursinus with large seams of cellular cementum and cementoid populated by contiguous cementoblasts indicate the continuous molecular cross-talk between cementum, newly formed cementoid matrix, cementoblasts and extracellular matrix soluble molecular signals. This molecular cross-talk may control the biomolecular homeostasis of both cementum and periodontal ligament, including angiogenesis. A further molecular scenario is invocated by the tight and exquisite anatomical relationships between the cementoid surfaces and the newly formed capillaries. The primitiveness of the craniate masticatory mineralized craniofacial apparatus has been controlled by several yet ancestral common genes not lastly the TGF-ß3 gene. The TGF-ß3 might have been responsible for the induction of cementogenesis not only in extant P. ursinus but also in Diatectomorpha and mosasaurs, thus providing continuous evolutionary mechanisms for the induction of tissue morphogenesis across animal phyla for almost a billion years of evolution, epitomizing Nature's parsimony in controlling tissue induction and morphogenesis. TGF-ß receptor II regulates osterix expression via Smad-dependent pathways indicating that TGF-ß signalling acts as an upstream regulator of osterix during cementoblast differentiation. The presence of morphogenetic signals within the cemental matrix capable of inducing bone formation needs now to be assigned: bone induction initiated by extracted and partially purified cemental matrices may be the result of a slow release of embryonic remnants of osteogenic signals required and deployed during cementogenesis. The cementum may thus rule the periodontal ligament space homeostasis, remodelling and repair by releasing sequestered morphogenetic signals that were deployed during embryogenesis.

Evolutionary relationships between seryl-histidine dipeptide and modern serine proteases from the analysis based on mass spectrometry and bioinformatics.

Seryl-histidine dipeptide (Ser-His) has been recognized as the shortest peptide with hydrolysis cleavage activity; however, its protein cleavage spectrum has not yet been fully explored. Here, four differently folded proteins were treated with Ser-His, and the digestion products were evaluated with high-resolution mass spectrometry. The cleavage efficiency and cleavage propensity of Ser-His against these protein substrates were calculated at both the primary and secondary sequence levels. The above experiments show that Ser-His cleaves a broad spectrum of substrate proteins of varying secondary structures. Moreover, Ser-His could cleave at all 20 amino acids with different efficiencies according to the protein, which means that Ser-His has the original digestion function of serine proteases. Furthermore, we collected and compared the catalytic sites and cleavage sites of 340 extant serine proteases derived from 17 representative organisms. A consensus motif Ser-[X]-His was identified as the major pattern at the catalytic sites of serine proteases from all of the organisms represented except Danio rerio, which uses Ser-Lys instead. This finding indicates that Ser-His is the core component of the serine protease catalytic site. Moreover, our analysis revealed that the cleavage sites of modern serine proteases have become more specific over the evolutionary history of this family. Based on the above analysis results, it could be found that Ser-His is likely the original serine protease and maybe the evolutionary core of modern serine proteases.

Apocrine secretion: New insights into an old phenomenon.

BACKGROUND: While apocrine secretion was among the earliest secretory mechanisms to be identified, its underlying basis remains poorly understood. SCOPE OF REVIEW: This review reappraises our understanding of apocrine secretion using insights about apocrine secretion from the salivary glands of Drosophila, in which molecular genetic analyses have provided a glimmer of hope for elucidating the mechanistic aspects of this fundamental process. MAJOR CONCLUSIONS: In contrast to the well-defined process of exocytosis, apocrine secretion is non-vesicular transport and secretory pathway that entails the loss of part of the cytoplasm. It often involves apical protrusions and generates cytoplasmic fragments inside a secretory lumen. In its most intense phase this process is accompanied by the release of large fragments of cellular structures and entire organelles that include mitochondria, Golgi, and portions of the endoplasmic reticulum, among others. Proteomic analyses revealed that the secretion is composed of hundreds to thousands of membranous, cytoskeletal, microsomal, mitochondrial, ribosomal, and even nuclear as well as nucleolar proteins. Strikingly, although many nuclear proteins are released, the nuclear deoxyribonucleic acid itself remains intact. In spite of this complexity, it appears that several protein components of apocrine secretion are identical, regardless of the location of the apocrine gland. GENERAL SIGNIFICANCE: This type of secretion appears to be common to many, if not all, barrier epithelial tissues including skin derivatives and the epididymis, and is implicated also in lung/bronchi and intestinal epithelium. Apocrine secretion is a mechanism that provides the en masse delivery of a very complex proteinaceous mixture from polarized epithelial tissues to allow for communication at exterior interfaces.

Shigella flexneri serotype 1c derived from serotype 1a by acquisition of gtrIC gene cluster via a bacteriophage.

BACKGROUND: Shigella spp. are the primary causative agents of bacillary dysentery. Since its emergence in the late 1980s, the S. flexneri serotype 1c remains poorly understood, particularly with regard to its origin and genetic evolution. This article provides a molecular insight into this novel serotype and the gtrIC gene cluster that determines its unique immune recognition. RESULTS: A PCR of the gtrIC cluster showed that serotype 1c isolates from different geographical origins were genetically conserved. An analysis of sequences flanking the gtrIC cluster revealed remnants of a prophage genome, in particular integrase and tRNA(Pro) genes. Meanwhile, Southern blot analyses on serotype 1c, 1a and 1b strains indicated that all the tested serotype 1c strains may have had a common origin that has since remained distinct from the closely related 1a and 1b serotypes. The identification of prophage genes upstream of the gtrIC cluster is consistent with the notion of bacteriophage-mediated integration of the gtrIC cluster into a pre-existing serotype. CONCLUSIONS: This is the first study to show that serotype 1c isolates from different geographical origins share an identical pattern of genetic arrangement, suggesting that serotype 1c strains may have originated from a single parental strain. Analysis of the sequence around the gtrIC cluster revealed a new site for the integration of the serotype converting phages of S. flexneri. Understanding the origin of new pathogenic serotypes and the molecular basis of serotype conversion in S. flexneri would provide information for developing cross-reactive Shigella vaccines.

Relation Between Obesity and Type 2 Diabetes: Evolutionary Insights, Perspectives and Controversies.

PURPOSE OF REVIEW: Since the mid-twentieth century, obesity and its related comorbidities, notably insulin resistance (IR) and type 2 diabetes (T2D), have surged. Nevertheless, their underlying mechanisms remain elusive. Evolutionary medicine (EM) sheds light on these issues by examining how evolutionary processes shape traits and diseases, offering insights for medical practice. This review summarizes the pathogenesis and genetics of obesity-related IR and T2D. Subsequently, delving into their evolutionary connections. Addressing limitations and proposing future research directions aims to enhance our understanding of these conditions, paving the way for improved treatments and prevention strategies. RECENT FINDINGS: Several evolutionary hypotheses have been proposed to unmask the origin of obesity-related IR and T2D, e.g., the "thrifty genotype" hypothesis suggests that certain "thrifty genes" that helped hunter-gatherer populations efficiently store energy as fat during feast-famine cycles are now maladaptive in our modern obesogenic environment. The "drifty genotype" theory suggests that if thrifty genes were advantageous, they would have spread widely, but proposes genetic drift instead. The "behavioral switch" and "carnivore connection" hypotheses propose insulin resistance as an adaptation for a brain-dependent, low-carbohydrate lifestyle. The thrifty phenotype theory suggests various metabolic outcomes shaped by genes and environment during development. However, the majority of these hypotheses lack experimental validation. Understanding why ancestral advantages now predispose us to diseases may aid in drug development and prevention of disease. EM helps us to understand the evolutionary relation between obesity-related IR and T2D. But still gaps and contradictions persist. Further interdisciplinary research is required to elucidate complete mechanisms.

Large-scale analysis of the ARF and Aux/IAA gene families in 406 horticultural and other plants.

The auxin response factor (ARF) and auxin/indole-3-acetic acid (Aux/IAA) family of genes are central components of the auxin signaling pathway and play essential roles in plant growth and development. Their large-scale analysis and evolutionary trajectory of origin are currently not known. Here, we identified the corresponding ARF and Aux/IAA family members and performed a large-scale analysis by scanning 406 plant genomes. The results showed that the ARF and Aux/IAA gene families originated from charophytes. The ARF family sequences were more conserved than the Aux/IAA family sequences. Dispersed duplications were the common expansion mode of ARF and Aux/IAA families in bryophytes, ferns, and gymnosperms; however, whole-genome duplication was the common expansion mode of the ARF and Aux/IAA families in basal angiosperms, magnoliids, monocots, and dicots. Expression and regulatory network analyses revealed that the Arabidopsis thaliana ARF and Aux/IAA families responded to multiple hormone, biotic, and abiotic stresses. The APETALA2 and serum response factor-transcription factor gene families were commonly enriched in the upstream and downstream genes of the ARF and Aux/IAA gene families. Our study provides a comprehensive overview of the evolutionary trajectories, structural functions, expansion mechanisms, expression patterns, and regulatory networks of these two gene families.

Evidence for cross-species transmission of human coronavirus OC43 through bioinformatics and modeling infections in porcine intestinal organoids.

Cross-species transmission of coronaviruses has been continuously posing a major challenge to public health. Pigs, as the major animal reservoirs for many zoonotic viruses, frequently mediate viral transmission to humans. This study comprehensively mapped the relationship between human and porcine coronaviruses through in-depth bioinformatics analysis. We found that human coronavirus OC43 and porcine coronavirus PHEV share a close phylogenetic relationship, evidenced by high genomic homology, similar codon usage patterns and comparable tertiary structure in spike proteins. Inoculation of infectious OC43 viruses in organoids derived from porcine small and large intestine demonstrated that porcine intestinal organoids (pIOs) are highly susceptible to human coronavirus OC43 infection and support infectious virus production. Using transmission electron microscopy, we visualized OC43 viral particles in both intracellular and extracellular compartments, and observed abnormalities of multiple organelles in infected organoid cells. Robust OC43 infections in pIOs result in a significant reduction of organoids viability and widespread cell death. This study bears essential implications for better understanding the evolutionary origin of human coronavirus OC43, and provides a proof-of-concept for using pIOs as a model to investigate cross-species transmission of human coronavirus.