The genetic code is evolutionarily conserved but can undergo lineage-specific alterations. Although mitochondrial UAA stop-to-Tyr codon reassignment has evolved independently in several metazoan lineages, its molecular basis remains poorly understood. As more species are sequenced, an increasing number of UAA stop-to-Tyr codon reassignments are being reported in new metazoan lineages, providing an important opportunity to integrate these cases and explore the molecular basis and evolutionary history of this reassignment. We generated a near-complete genome assembly of the cementing bivalve Anomia chinensis, a member of the understudied bivalve superfamily Anomioidea (Bivalvia, Mollusca), comprising 572.90 Mb with a contig N50 of 79.37 Mb and 7 chromosomes. A genome-based phylogeny reconstructed from the major lineages of Pteriomorphia supported that Pectinida is not monophyletic. We also reconstructed the bivalve ancestral linkage groups (BiLGs, n = 20) and performed macrosynteny analysis, which revealed that, within Pteriomorphia, cementing bivalves in the intertidal zone exhibited significantly lower conservation of ancestral karyotypes compared to other groups. Furthermore, we presented the first evidence of mitochondrial UAA stop-to-Tyr codon reassignment in bivalves. We further revealed the genetic basis underlying this reassignment in metazoan mitochondrial genomes, which generally requires the co-evolution of mtRF1a and tRNAs. In this study, we provided essential genomic resources for A. chinensis and reconstructed the BiLGs of bivalves, advancing our understanding of bivalve phylogeny and chromosomal macrosynteny evolution. Importantly, the parallel mutations identified in mtRF1a and tRNATyrGUA in both hemichordates and mollusks may offer valuable insights into genetic code reprogramming of mitochondria in metazoans, and potentially across a broader range of cellular life.
Due to the scarcity or incomplete preservation of structures, fossils that can be compared with extant insects and directly reflect the evolution of survival strategies are extremely rare. Extant stick and leaf insects are renowned for their remarkable plant mimicry (mimesis), yet their active defensive behavior is rare and its origin and early evolutionary history remain unclear. We report two new stick insect species, Coniphasma inflatum sp. nov. and C. breve sp. nov. of the family Susumaniidae, from the Early Cretaceous Jehol Biota ( 125 Ma) of China. Both species have enlarged hind femora that are significantly larger than those of other known species in this group, indicating the function for active defense. Moreover, besides the irregular color markings on their well-developed wings and enlarged femora that aid in camouflage, the legs of these two species are armed with prominent longitudinal carinae bearing rows of denticulate notches, suggesting the enhancement of active defensive strategy employed after camouflage has failed. These fossils demonstrate that the origin of hind femora enlargement probably predates wing regression in Phasmatodea. This discovery suggested that the highly diverse morphological characters observed in living stick insects were already established by the Mesozoic, and these features have evolved independently multiple times within Phasmatodea.
Over the past two decades, failures to replicate published findings in biomedical research have led to a perceived reproducibility crisis. Several interventions at the level of inferential statistics and experimental design have been proposed for improving reproducibility. These include raising the power by increasing the sample size, redefining the threshold for statistical significance, focusing on a minimally important difference, adding a penalising term for between-study variation, and combining data from multiple study centres. We used simulations to investigate the effectiveness of these interventions on measures of reproducibility. Artificial data sets were created by repeatedly sampling from defined parametric distributions based on published biomedical studies (i.e. real-world data sets). Reproducibility measures included the probability of positive findings, the probability of consistent inferential outcomes and the chance of capturing the true effect size. The results were mixed: some of the proposed interventions could improve reproducibility, while others had detrimental effects on reproducibility. Notably, the interventions affected the various aspects of reproducibility differently.
Mobile genetic elements (MGEs), including viruses, plasmids, and transposons, are major drivers of evolution in bacteria and archaea. Host-parasite conflicts drive the emergence of a broad variety of defense and counter-defense systems. Recent advances in metagenomics and functional annotation have shown that many defense systems are located on MGEs. The fact that MGEs are, essentially, genomic parasites raises an intriguing question: why do these parasites carry defense systems at high prevalence, often even higher than the host chromosome? We developed a simple mathematical model to investigate the factors that promote evolution of defense systems in MGEs and the ecological implications of MGE-encoded defense. Our analysis points to the strength of inter-MGE interference as a key determinant of the evolution of defense systems in MGEs. We identify two qualitatively distinct regimes, depending on the basic reproductive number in mixed coinfections. Weakly interfering MGEs tend to carry low-cost defense systems that enhance the survival of their hosts upon exposure to more damaging MGEs. Although these systems can be occasionally transferred to the host, they typically remain in MGEs. In contrast, strongly interfering MGEs, such as plasmids from the same incompatibility group, can carry high-cost defense systems that are detrimental to the host and the population as a whole, but help their carriers spread by actively replacing their competitors. Analysis of our model suggests that the key determinant of the evolution and spread of defense systems in MGEs is the strength of cross-MGE interference. We hypothesize that weakly interfering MGEs would serve as “defense banks,” typically carrying low-cost defense systems that can benefit the host by protecting it from more damaging MGEs. In contrast, strongly interfering MGEs would carry costly defense systems that mediate inter-MGE conflicts but are deleterious to the host. These MGEs could serve as proving ground for emerging defense systems, which might eventually become cost-effective once optimized by selection.
Ceramides are central sphingolipid intermediates whose abundance and molecular composition are closely linked to insulin resistance. Ceramide synthases (CerSs) generate ceramides and, in several family members, also contain a conserved homeodomain with poorly understood metabolic functions. Drosophila has a single CerS, Schlank, which contains a catalytic Lag1p motif and two predicted nuclear localization sequences, NLS1 and NLS2. We investigated how distinct Schlank homeodomain mutations affect high-sugar diet (HSD)-induced insulin resistance. Endogenous KINLS1 and KIE118A knock-in alleles retained DNA binding and transcriptional repression under basal conditions but increased susceptibility to HSD-induced metabolic dysfunction. Both mutants developed enhanced hyperglycemia and impaired insulin-responsive tGPH recruitment, while KIE118A additionally showed increased FoxO nuclear localization and DILP2 retention in insulin-producing cells. By contrast, fat-body-specific switching to the DNA-binding-deficient NLS2 variant or the catalytically inactive H215D variant attenuated selected HSD-induced phenotypes, including FoxO nuclear accumulation and DILP2 retention, without fully correcting hyperglycemia or reduced body weight. Lipidomic analysis revealed extensive diet-dependent sphingolipid remodeling. In particular, NLS2 and H215D markedly reduced the fat-body ceramide pool, including abundant d14:1/20:0- and d14:1/22:0-containing Cer, CerPE, and HexCer species. The Schlank homeodomain regulates insulin homeostasis in a site- and tissue-dependent manner. Distinct homeodomain mutations can either increase susceptibility to or partially attenuate HSD-induced insulin resistance, potentially involving insulin signaling, inter-organ communication, and sphingolipid composition.
