In the absence of nuclear-genomic differentiation between two populations, deep mitochondrial divergence (DMD) is a form of mito-nuclear discordance. Such instances of DMD are rare and might variably ...be explained by unusual cases of female-linked selection, by male-biased dispersal, by "speciation reversal" or by mitochondrial capture through genetic introgression. Here, we analyze DMD in an Asian Phylloscopus leaf warbler (Aves: Phylloscopidae) complex. Bioacoustic, morphological, and genomic data demonstrate close similarity between the taxa affinis and occisinensis, even though DMD previously led to their classification as two distinct species. Using population genomic and comparative genomic methods on 45 whole genomes, including historical reconstructions of effective population size, genomic peaks of differentiation and genomic linkage, we infer that the form affinis is likely the product of a westward expansion in which it replaced a now-extinct congener that was the donor of its mtDNA and small portions of its nuclear genome. This study provides strong evidence of "ghost introgression" as the cause of DMD, and we suggest that "ghost introgression" may be a widely overlooked phenomenon in nature.
When different species experience similar selection pressures, the probability of evolving similar adaptive solutions may be influenced by legacies of evolutionary history, such as lineage-specific ...changes in genetic background. Here we test for adaptive convergence in hemoglobin (Hb) function among high-altitude passerine birds that are native to the Qinghai-Tibet Plateau, and we examine whether convergent increases in Hb–O₂ affinity have a similar molecular basis in different species. We documented that high-altitude parid and aegithalid species from the Qinghai-Tibet Plateau have evolved derived increases in Hb–O₂ affinity in comparison with their closest lowland relatives in East Asia. However, convergent increases in Hb–O₂ affinity and convergence in underlying functional mechanisms were seldom attributable to the same amino acid substitutions in different species. Using ancestral protein resurrection and site-directed mutagenesis, we experimentally confirmed two cases in which parallel substitutions contributed to convergent increases in Hb–O₂ affinity in codistributed high-altitude species. In one case involving the ground tit (Parus humilis) and gray-crested tit (Lophophanes dichrous), parallel amino acid replacements with affinity-enhancing effects were attributable to nonsynonymous substitutions at a CpG dinucleotide, suggesting a possible role for mutation bias in promoting recurrent changes at the same site. Overall, most altitude-related changes in Hb function were caused by divergent amino acid substitutions, and a select few were caused by parallel substitutions that produced similar phenotypic effects on the divergent genetic backgrounds of different species.
Aim
The Pleistocene glacial cycles play a prominent role in shaping phylogeographical patterns of organisms, while few studies have focused on the regional difference of glacial effects. By acquiring ...comprehensive knowledge of the origin, diversification and historical demography of an intensively studied passerine species complex, Great Tit, we aim to test the regional variation of the Late Pleistocene glaciation impacts on this widely distributed bird lineage.
Location
Eurasia and associated peninsulas and archipelagos.
Taxa
Parus major species complex.
Methods
Phylogeny, divergence times and demographic dynamics were estimated with Bayesian methods. Population structure, genetic diversity and correlation between genetic and physical distances were estimated based on mtDNA variation. Glacial‐to‐present distributional changes were assessed via ecological niche modelling (ENM).
Results
Five major clades (Central Asia, Eastern Asia, Eastern Himalaya, Northern and Western Eurasia and Southern Asia) were detected, with divergence times ranging 1.57–0.50 million years ago. Genetic diversity values and Bayesian skyline plots suggest that the three eastern clades had a deeper population history. A more complex geographic structure was observed in East Asia. Demographic expansion during the last glacial cycle was indicated for all five clades. ENM results showed broad conservatism of traits related to climate tolerances, and generally broader and more continuous distributional patterns under glacial conditions.
Main Conclusions
The Great Tit complex probably originated in Southeast Asia. Geographic barriers, such as the deserts of Central Asia and the Qinghai–Tibet Plateau appear to be related to the lineage divergence. Late Pleistocene climate cycles influenced both demographic dynamics and divergence, especially in terms of east–west differences in relation to geographic complexity.
Genomic data are important for understanding the origin and evolution of traits. Underthe context of rapidly developing of sequencing technologies and more widely available genome ...sequences,researchers are able to study evolutionary mechanisms of traits via comparative genomicmethods. Compared with other vertebrates, bird genomes are relatively small and exhibitconserved synteny with few repetitive elements, which makes them suitable for evolutionarystudies. Increasing genomic progress has been reported on the evolution of powered flight, bodysize variation, beak morphology, plumage colouration, high-elevation colonization, migration, andvocalization. By summarizing previous studies, we demonstrate the genetic bases of trait evolution,highlighting the roles of small-scale sequence variation, genomic structural variation, and changesin gene interaction networks. We suggest that future studies should focus on improving the qualityof reference genomes, exploring the evolution of regulatory elements and networks, and combininggenomic data with morphological, ecological, behavioural, and developmental biology data.
Skeletal muscle plays a central role in regulating glucose uptake and body metabolism; however, highland hypoxia is a severe challenge to aerobic metabolism in small endotherms. Therefore, ...understanding the physiological and genetic convergence of muscle hypoxia tolerance has a potential broad range of medical implications. Here we report and experimentally validate a common physiological mechanism across multiple high-altitude songbirds that improvement in insulin sensitivity contributes to glucose homeostasis, low oxygen consumption, and relative activity, and thus increases body weight. By contrast, low-altitude songbirds exhibit muscle loss, glucose intolerance, and increase energy expenditures under hypoxia. This adaptive mechanism is attributable to convergent missense mutations in the BNIP3L gene, and METTL8 gene that activates MEF2C expression in highlanders, which in turn increases hypoxia tolerance. Together, our findings from wild high-altitude songbirds suggest convergent physiological and genetic mechanisms of skeletal muscle in hypoxia resistance, which highlights the potentially medical implications of hypoxia-related metabolic diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To determine the prognostic value of cumulative calcification score of coronary artery calcification (CAC), thoracic aortic calcification (TAC) and aortic valve calcification (AVC) in acute ST ...segment elevation myocardial infarction (STEMI) patients.
This was a retrospective, single-center cohort study. A total of 332 STEMI patients who received primary percutaneous coronary intervention (PPCI) were enrolled in this study between January 2010 to October 2018. We assessed the calcification in the left anterior descending branch (LAD), left circumflex branch (LCX), right coronary artery (RCA), thoracic aorta, and aortic valve. Calcification of each part was counted as 1 point, and the cumulative calcification score was calculated as the sum of all points. The primary endpoint was all-cause mortality. Multivariate Cox proportional hazards models were used to determine association of cumulative calcification score with end points. The performance of the score was evaluated by receiver operating characteristic (ROC) curve analysis and absolute net reclassification improvement (NRI), compared with the Global Registry of Acute Coronary Events (GRACE) risk score.
The overall population's calcification score was 2.0 ± 1.6. During a mean follow-up time of 69.8 ± 29.3 months, the all-cause mortality rate was 12.1%. Kaplan-Meier curve showed that the score was significantly associated with mortality (log-rank p < 0.001). The multivariable Cox proportional hazard analyses showed that a calcification score of 4-5 was independently associated with all-cause death in STEMI patients hazard ratio (HR) = 2.32, 95% confidence interval (CI): 1.01-5.31, p = 0.046. The area under the ROC curve (AUC) of the calcification score was 0.67 (95% CI: 0.61-0.72), and the AUC of the GRACE score was 0.80 (95% CI: 0.75-0.84). There was no statistical difference in the predictive value between both scores for 3-year mortality in STEMI patients after PPCI (p = 0.06). Based on the NRI analysis, the calcification score showed better risk classification compared with the GRACE score (absolute NRI = 6.63%, P = 0.027).
The cumulative calcification score is independently associated with the long-term prognosis of STEMI patients after PPCI.
Introduction
Heart failure (HF) with preserved ejection fraction (HFpEF) has become the main type of HF worldwide. Although large randomised controlled studies have demonstrated the beneficial ...effects of sodium–glucose cotransporter 2 inhibitors among patients with HFpEF, the mechanisms remain unclear. Basic research suggests that empagliflozin inhibits myocardial fibrosis. Myocardial extracellular volume (ECV) can be calculated using cardiac MRI (CMRI), which can reflect the degree of diffuse myocardial fibrosis. Studies show that empagliflozin can reduce ECV and left ventricular mass (LVM) assessed by CMRI in patients with diabetes with coronary heart disease and patients without diabetes with HF with reduced ejection fraction. However, whether empagliflozin reduces ECV and LVM among patients with HFpEF is unclear. This study intends to use CMRI to evaluate ECV and LVM, combined with echocardiography and an assessment of related biomarkers, to determine whether empagliflozin can improve myocardial fibrosis and left ventricular remodelling in patients with HFpEF.
Methods and analysis
This report describes the study design of a prospective, multicentre, randomised, double-blind, placebo-controlled and parallel-group clinical study. A total of 180 participants with HFpEF aged 40–80 years old who meet the inclusion and exclusion criteria will be randomly divided into an empagliflozin treatment group or a placebo control group. The empagliflozin treatment group will receive 10 mg of empagliflozin per day for 6 months in addition to guideline-directed medical treatment, while the control group will receive placebo oral administration with guideline-directed medical therapy for 6 months. The primary outcomes are ECV and LVM changes measured by CMRI after 6 months of treatment.
Ethics and dissemination
The study design is approved by the ethical committee of Beijing Hospital (2022BJYYEC-070-02). The trial is registered at the Chinese Clinical Trial Registry (
http://www.chictr.org.cn
). The trial results will be published in peer-reviewed journals and conferences.
Trial registration number
Chinese Clinical Trial Registry (ChiCTR2200060862).
Background/Aims: Genomic adaptations to high altitudes have been well studied in the last several years; however, the roles of microRNAs (miRNAs), which are essential modulators of a variety of genes ...and key cellular processes, have rarely been explored. Here, we explored the interactions between miRNAs and their target genes as an adaptation to high altitude in an avian species, the great tit (Parus major), which is widely distributed across the Eurasian continent at altitudes between 4500 m and sea level. Because the MAPK signaling pathway plays a crucial role in the hypoxia response in the great tit, we chose MAPK1 as a target candidate gene. Methods: We established a great tit embryonic fibroblast line and subsequently studied the relationship between miRNA-19b-3p and MAPK1 in normoxia and hypoxia groups. Meanwhile, the great tit embryonic fibroblasts (GEFs) were treated or transfected with miR-19b-3p mimics, inhibitors, or si-MAPK1, and their proliferation was subsequently assessed using the MTT assay. The expression of the miRNAs and MAPK1 was measured by real-time PCR and Western blotting. Results: We identified 14 miRNAs in the cardiac tissues of great tits that are related to hypoxia adaptation. MAPK1 binds only to miR-19b-3p of the 14 miRNAs predicted by both TargetScan and miRanda software. Specifically, we validated the computational prediction of miR-19b-3p binding to the 3’UTR of MAPK1 using a luciferase reporter assay. Our results show that miR-19b-3p promotes GEFs proliferation and up-regulates MAPK1 expression. Moreover, miR-19b-3p mimics and MAPK1 knockdown induce GEFs apoptosis and regulate the cell cycle under hypoxic conditions. Conclusions: Our study is the first to describe an important miRNA-mediated regulatory mechanism of high altitude adaptation in a non-model wild songbird and highlights the importance of studies on miRNA-mediated mechanisms of hypoxic adaptations in other animals.
The phenotypic plasticity in responses to short-term stress can provide clues for understanding the adaptive fixation mechanism of genetic variation during long-term exposure to extreme environments. ...However, few studies have compared short-term stress responses with long-term evolutionary patterns; in particular, no interactions between the two processes have been evaluated in high-altitude environment. We performed RNA sequencing in embryo fibroblasts derived from great tits and mice to explore transcriptional responses after exposure to simulated high-altitude environmental stresses. Transcriptional changes of genes associated with metabolic pathways were identified in both bird and mice cells after short-term stress responses. Genomic comparisons among long-term highland tits and mammals and their lowland relatives revealed similar pathways (e.g., metabolic pathways) with that initiated under short-term stress transcriptional responses in vitro. These findings highlight the indicative roles of short-term stress in the long-term adaptation, and adopt common paths to molecular adaptation in mouse and bird cells.
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•Short-term stress and long-term adaptations share the common metabolic pathways•Phenotypic plasticity can promote adaptive evolution•Adopt common paths to molecular adaptation in mouse and bird cells
Biological sciences; Genetics; Genomics; Cell biology
Beak morphology exhibits considerable adaptive plasticity in birds, which results in highly varied or specialized forms in response to variations in ecology and life history. As the only parid ...species endemic to the Qinghai-Tibet Plateau, the Ground Tit (
) has evolved a distinctly long and curved beak from other parids. An integration of morphometrics, phylogenetics, transcriptomics and embryology allows us to address the evolutionary and developmental mechanisms of the adaptive beak structure observed in the Ground Tit.
A morphometric approach quantified that the Ground Tit has a comparatively longer and more decurved upper beaks than other parids. We estimated that the ancestor of the Ground Tit likely had a short straight upper beak similar to most current recognized parid species using an ancestral state reconstruction. This morphological specialization is considered an adaptation to its ground-oriented behavior on the high plateau. To identify genetic mechanisms behind this adaptive change, a comparative transcriptomic analysis was applied between the Ground Tit and its closely related species, the Great Tit (
). We detected that 623 genes were significantly differentially expressed in embryonic upper beaks between the two species, 17 of which were functionally annotated to correlate with bone development and morphogenesis, although genes related to bone development were not found to undergo accelerated evolution in the Ground Tit. RT-qPCR validation confirmed differential expression of five out of eight genes that were selected from the 17 genes. Subsequent functional assays in chicken embryos demonstrated that two of these genes,
and
, may affect beak morphology by modulating levels of osteoblasts and osteoclasts.
Our results provide preliminary evidence that development of the long decurved beak of the Ground Tit is likely regulated by transcriptional activities of multiple genes coordinating osteoblasts and osteoclasts. The integration of multiple approaches employed here sheds light on ecological and genetic mechanisms in the evolution of avian morphology.
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