RESUMO
Angiotensin-convertingenzyme 2 (ACE2) has dual functions, regulating cardiovascular physiology and serving as the receptor for coronaviruses. Bats, the only true flying mammals and natural viral reservoirs, have evolved positive alterations in traits related to both functions of ACE2. This suggests significant evolutionary changes in ACE2 during bat evolution. To test this hypothesis, we examine the selection pressure in ACE2 along the ancestral branch of all bats (AncBat-ACE2), where powered flight and bat-coronavirus coevolution occurred, and detect a positive selection signature. To assess the functional effects of positive selection, we resurrect AncBat-ACE2 and its mutant (AncBat-ACE2-mut) created by replacing the positively selected sites. Compared to AncBat-ACE2-mut, AncBat-ACE2 exhibits stronger enzymatic activity, enhances mice's performance in exercise fatigue, and shows lower affinity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our findings indicate the functional pleiotropy of positive selection in the ancient ACE2 of bats, providing an alternative hypothesis for the evolutionary origin of bats' defense against coronaviruses.
Assuntos
Enzima de Conversão de Angiotensina 2 , Quirópteros , Seleção Genética , Quirópteros/virologia , Quirópteros/genética , Animais , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Camundongos , Pleiotropia Genética , Evolução Molecular , SARS-CoV-2/genética , COVID-19/virologia , COVID-19/genética , Coronavirus/genética , Humanos , FilogeniaRESUMO
Efficient ultraviolet (UV) electroluminescent materials remain a great challenge, since short peak wavelength <400â nm and narrow full width at half maximum (FWHM) <50â nm are simultaneously required. In this sense, multi-resonance (MR) thermally activated delayed fluorescence (TADF) emitters featuring narrow-band emissions hold the promise for UV applications. Herein, a novel MR-TADF skeleton featuring carbazole-phosphine oxide (P=O) fused aromatics is developed to construct the first two UV MR emitters named CzP2PO and tBCzP2PO. In addition to synergistic resonance effects of P=O and N atom, sp3 -hybrid P atom renders the curved polycyclic planes of CzP2PO and tBCzP2PO, giving rise to their narrowband UV emissions with peak wavelengths <390â nm and FWHM<35â nm. Besides configuration quasi-planarization for radiation enhancement and quenching suppression, P=O moiety further enhances singlet-triplet coupling to facilitate reverse intersystem crossing, resulting in the state-of-the-art photoluminescence quantum yield of 62 % in tBCzP2PO doped films. As consequence, tBCzP2PO endowed its UV organic light-emitting diodes with the peak at 382â nm and FWHM of 32â nm, and especially the record-high external quantum efficiency (EQE) of 15.1 % among all kinds of UV devices. Our results demonstrate great potential of P=O based MR emitters in practical applications including optoelectronics, biology and medicine science.
RESUMO
The evolutionary outcomes of high elevation adaptation have been extensively described. However, whether widely distributed high elevation endemic animals adopt uniform mechanisms during adaptation to different elevational environments remains unknown, especially with respect to extreme high elevation environments. To explore this, we analysed the phenotypic and genomic data of seven populations of plateau zokor (Myospalax baileyi) along elevations ranging from 2,700 to 4,300 m. Based on whole-genome sequencing data and demographic reconstruction of the evolutionary history, we show that two populations of plateau zokor living at elevations exceeding 3,700 m diverged from other populations nearly 10,000 years ago. Further, phenotypic comparisons reveal stress-dependent adaptation, as two populations living at elevations exceeding 3,700 m have elevated ratios of heart mass to body mass relative to other populations, and the highest population (4,300 m) displays alterations in erythrocytes. Correspondingly, genomic analysis of selective sweeps indicates that positive selection might contribute to the observed phenotypic alterations in these two extremely high elevation populations, with the adaptive cardiovascular phenotypes of both populations possibly evolving under the functional constrains of their common ancestral population. Taken together, phenotypic and genomic evidence demonstrates that heterogeneous stressors impact adaptations to extreme elevations and reveals stress-dependent and genetically constrained adaptation to hypoxia, collectively providing new insights into the high elevation adaptation.
Assuntos
Adaptação Fisiológica , Hipóxia , Aclimatação , Adaptação Fisiológica/genética , Animais , Genômica , FenótipoRESUMO
Comparative plastomics can be used to explicitly dissect various types of plastome variation. In the present study, the plastome variation pattern of Ziziphus jujuba var. spinosa (also called sour jujube) and its phylogenomic relationship with Chinese jujube were investigated. Plastomes of 21 sour jujube individuals were sequenced and assembled. The length of the sour jujube plastomes ranged between 159399 and 161279 bp. The plastomes exhibited collinearity of structure, gene order and content. The most divergent regions were located in the intergenic spacers, such as trnR-UCU-atpA and psbZ-trnG-UCC. Sliding window analysis demonstrated that the sequence variation among the sour jujube plastomes was relatively low. Sixty-two to 76 SSRs with 4 motif types were identified in the sour jujube plastomes with a predominant motif type of A/T. Three protein-coding genes exhibited higher nonsynonymous/synonymous substitution ratios, indicating that these genes may undergo positive selection. A total of 80 SNPs were detected and 1266 potential RNA editing sites of 23 protein-coding genes were predicted. In the phylogenomic tree constructed, sour jujube has a sister relationship to Chinese jujube, which indicates that Chinese jujube may have originated or been domesticated from sour jujube. The present study explicitly investigated the individual-level plastome variation of sour jujube and provides potential valuable molecular markers for future genetic-related study of this lineage.
RESUMO
Sensorineural hearing loss (SNHL) is referred to as the most common type of hearing loss and typically occurs when the inner ear or the auditory nerve is damaged. Aging, noise exposure, and ototoxic drugs represent three main causes of SNHL, leading to substantial similarities in pathophysiological characteristics of cochlear degeneration. Although the common molecular mechanisms are widely assumed to underlie these similarities, its validity lacks systematic examination. To address this question, we generated three SNHL mouse models from aging, noise exposure, and cisplatin ototoxicity, respectively. Through constructing gene co-expression networks for the cochlear transcriptome data across different hearing-damaged stages, the three models are found to significantly correlate with each other in multiple gene co-expression modules that implicate distinct biological functions, including apoptosis, immune, inflammation, and ion transport. Bioinformatics analyses reveal several potential hub regulators, such as IL1B and CCL2, both of which are verified to contribute to apoptosis accompanied by the increase of (ROS) in in vitro model system. Our findings disentangle the shared molecular circuits across different types of SNHL, providing potential targets for the broad effective therapeutic agents in SNHL.
RESUMO
The laryngeal echolocation is regarded as one of the conspicuous traits that play major roles in flourishing bats. Whether the laryngeal echolocation in bats originated once, however, is still controversial. We here address this question by performing molecular convergence analyses between ancestral branches of bats and toothed whales. Compared with controls, the molecular convergences were enriched in hearing-related genes for the last common ancestor of bats (LCAB) and extant echolocating bats, but not for the LCA of Old World fruit bats (LCAP). And the convergent hearing gene prestin of the LCAB and the extant echolocating bats functionally converged. More importantly, the high-frequency hearing of the LCAP-prestin knock-in mice decreased with lower cochlear outer hair cell function compared with the LCAB-prestin knock-in mice. Together, our findings provide multiple lines of evidence suggesting a single origin of laryngeal echolocation in the LCAB and the subsequent loss in the LCAP.
RESUMO
All extant species in the rodent family Spalacidae are subterranean and have evolved various traits for underground life. However, the phylogenomic relationships among its three subfamilies (Myospalacinae, Spalacinae, and Rhizomyinae) and the molecular basis underlying their adaptations to underground life remain poorly understood. Here, we inferred the phylogenomic relationships among these subfamilies based on de novo sequencing the genome of the hoary bamboo rat ( Rhizomys pruinosus). Analyses showed that ~50% of the identified 11 028 one-to-one orthologous protein-coding genes and the concatenated sequences of these orthologous genes strongly supported a sister relationship between Myospalacinae and Rhizomyinae. The three subfamilies diversified from each other within ~2 million years. Compared with the non-subterranean controls with similar divergence dates, the spalacids shared more convergent genes with the African subterranean mole-rats at the genomic scale due to more rapid protein sequence evolution. Furthermore, these convergent genes were enriched in the functional categories of carboxylic acid transport, vascular morphogenesis, and response to oxidative stress, which are closely associated with adaptations to the hypoxic-hypercapnic underground environment. Our study presents a well-supported phylogenomic relationship among the three subfamilies of Spalacidae and offers new insights into the molecular adaptations of spalacids living underground.