Journal of Genetics最新文献

High-altitude ecosystems in the Himalayas exhibit extreme seasonal variations in their vegetation, with summer and winter presenting the most pronounced environmental contrasts. As winter progresses, temperatures drop, and deciduous plant species undergo senescence. This study unravels the transcriptomic dynamics driving leaf senescence in Himalayan treeline species, Betula utilis, during seasonal variations. Using the RNA-sequence technology, leaf samples collected under fresh and senescent stages were analysed to deduce expression profiles at different stages. A total of 6505 differentially expressed transcripts were identified, with functional annotations revealing key senescence pathways such as phytohormonal regulation, chlorophyll degradation, and nutrient remobilisation. The upregulation of senescence-associated genes (SAGs), alongside alterations in transcription factors like WRKY and hormonal pathways, highlights the molecular interplay driving seasonal adaptation. Additionally, chlorophyll catabolism, modulated by NYC1 and PAO, was observed as a pivotal response to winter conditions. The findings of the study provide insights into the importance of carbohydrate metabolism, hormonal signalling, and stress adaptation-related pathways in nutrient conservation and plant fitness under environmental stress. This study offers a comprehensive understanding of the genetic mechanisms that allow B. utilis to withstand the harsh Himalayan climate, adding invaluable information to the fields of plant senescence, stress physiology, and climate resilience.

Ageing involves deterioration in physiological processes, such as maintenance of neuronal health, muscle, fat bodies, and gut bacteria, which play a crucial role in the progression of ageing. In this study, we show that the expression of Taxi, a transcription factor is required to maintain the lifespan in Drosophila melanogaster. Hypermorphic and hypomorphic alleles of taxi show reduced lifespan. We have identified that pan-neuronal overexpression and knockdown of Taxi lead to a stark reduction in the lifespan. In our previous study, we showed that Taxi negatively regulates Adar. Interestingly, overexpression of Adar significantly rescued the reduction in lifespan caused by taxi overexpression in neurons. Conversely, the knockdown of Adar rescued the defective lifespan caused by taxi knockdown in neurons. We show that enzymatically inactive Adar also rescued the reduced lifespan in flies having a neuronal taxi overexpression background. Our work suggests that, besides the editing activity, Adar may have editing-independent roles implicated in lifespan regulation. Overall, we show that neuronal tissue-specific controlled expression of taxi and its interacting partner Adar is imperative in lifespan maintenance.

The Chhattisgarh duck (Anas platyrhynchos L., 1758) is a native Indian germplasm that provides crucial support for the local food security and livelihoods in the eastern region of India. For sustainable use, preservation and conservation, it is crucial to understand its genetic identity and relationships with other breeds of duck. This study focuses on the identification of mitochondrial genome sequence of Chhattisgarh duck. The complete genome of the Chhattisgarh duck is 16,604-bp long, with 37 genes arranged in the same order and on the same strands as those in other species and breeds of Anas. Phylogenetic analysis shows that the Chhattisgarh duck is the sister to a group comprising multiple Mallard breeds and the Maithili breed as sister group, within a structure (((('Mallard' + Maithili) + Chhattisgarh) + Bengal) + Bihar), in which Bihar is the sister to all other known breeds of A. platyrhynchos. The germplasm of Maithili, Chhattisgarh, Bengal, and Bihar ducks are phenotypically as well as phylogenetically distinctive. This study shows the importance of identification and conservation of native Indian duck germplasm.

Schimke immunoosseous dysplasia (SIOD) is an uncommon inherited genetic disorder resulting from pathogenic variants in the SMARCAL1 gene. This complex condition exhibits a wide range of clinical features, including skeletal abnormalities, steroid-resistant nephrotic syndrome, and immune system deficiencies. In this study, we report a case series of three patients diagnosed with SIOD, each harbouring copy number variants in the SMARCAL1 gene. The cases expand the current understanding of the genetic diversity underlying SIOD and highlight the significance of copy number variations as a pathogenic mechanism. Our findings contribute to broadening the genotypic spectrum associated with SIOD and underscore the importance of comprehensive genetic analysis for accurate diagnosis and management of this rare disorder.

Cetuximab has been indicated as the mainstay of metastatic colorectal cancer (CRC) therapy, of which application was impeded by chemoresistance that was casually attributed to KRAS mutation. This study sought to determine whether YY1 mediated the resistance of CRC cells harbouring KRAS mutation (KRASmut) to cetuximab. The expression of YY1 between cetuximab response and resistance was investigated in cancerous tissues from CRC patients received cetuximab therapy comprising eight KRAS wild-type (KRASwt) and 12 KRASmut. The relationship between YY1 expression and cetuximab resistance was explored based on KRASmut and KRASwt CRC cell lines. To explore the role of YY1 in the cetuximab resistance of KRASmut CRC cells, the response to cetuximab was investigated in cetuximab-resistant cells (SW620-R) with YY1 silence and cetuximab sensitive cells (HCT116) with YY1 overexpression. EGFR/Akt/ERK signalling activation, as well as mRNA and active GTP-bound KRAS level were assessed after the treatment. In KRASmut CRC tissues, YY1 expression was correlated with the histological grade and the cetuximab resistance. Significantly markable differences in YY1 expression between cetuximab-resistant and the parental cell lines were found in KRASmut cells. Silencing YY1 resensitized SW620-R cells to cetuximab and led to an elevation of the active GTP-binding KRAS. Conversely, the capability against cetuximab and GTP-binding KRAS activation of HCT116 cells was enhanced by overexpressing YY1. The blockage of EGFR/Akt/ERK signalling by cetuximab was re-observed in SW620-R cells after silencing YY1 but impaired in HCT116 by overexpressing YY1. The YY1 mediates the resistance of KRASmut CRC cells to cetuximab.

The nonexpressor of pathogenesis-related 1 (NPR1) is the salicylic acid (SA) receptor, which plays an important regulatory role in plant immunity. However, the NPR1-like gene family in maize has not been comprehensively identified and analysed. In the present study, we identified gene structures, conserved motifs, cis-elements, and expression patterns in different tissues and organs, and under biotic and abiotic stresses. The NPR1-like proteins of different species are highly conserved during evolution. Many cis-acting elements have been identified in the promoter region of NPR1-like genes in maize, including elements that respond to growth and development, biotic and abiotic stresses, and plant hormones. Furthermore, the transcript abundance of all NPR1-like genes in maize changed significantly under abiotic treatments (cold, heat, salt, or drought treatments), phytohormone treatments and pathogen treatment (Ustilago maydis), indicating that they might be involved in biotic and abiotic stresses. In addition, ZmNPR1 is located in the cytoplasm, and overexpression of ZmNPR1 improves the resistance of maize plants to U. maydis. The findings of the present study might provide important information on under standing the complexity of the NPR1-like genes and their functions in maize.

After the arrival of the CRISPR/Cas9 genome editing technology, genetic engineering of model organisms has become much faster and more efficient. The development of genetically modified mouse models is also facilitated by the application of various CRISPR methodologies. Although the very first studies utilized pronuclear injection (PNI) of Cas9 mRNA and sgRNAs into the zygote stage embryos to create knockout and knockin mutations, the repertoire of techniques and collection of reagents for CRISPR editing has rapidly expanded. This presents researchers in the field with a versatility of choices for genetic engineering. However, there are not many comparative studies that analysed the efficacy of gene editing when Cas9 and sgRNA/ssDNA oligos were transferred to the embryos by different methodologies. Here, we aimed to compare two different methods, electroporation and PNI. One of the recent developments gaining wide use in mouse model research is the application of electroporation for the introduction of Cas9/sgRNA ribonucleoprotein complexes into zygote stage embryos. Here, we have used this technique to generate albino coat-coloured C57BL/6J mice by targeted inactivation of the mouse tyrosinase gene through indel or knockin mutations. We have also applied the PNI protocol with the same set of reagents, to compare the efficiency of the two techniques in generation of indel and knockin mutations. Although PNI results in signifi- cantly higher efficiency for knockin mutations, it requires specialized equipment setup and advanced training in embryo micromanipulation and microinjection. Therefore, for the generation of simple gene knockouts by indel mutations, electroporation can be used.

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited bone marrow failure syndrome, which is characterized by a severe thrombocytopenia at birth without predictive stigmata and by a risk for progression into aplastic anaemia and myeloid malignancy. While CAMT primarily arises from mutations in the MPL gene, recent discoveries have linked biallelic THPO mutations to some CAMT cases. In addition, loss of function monoallelic mutations in this gene have been identified as causing benign autosomal dominant thrombocytopenia. In this study, we report a case of CAMT linked to a homozygous mutation in the promoter region of THPO (c.-324C>T, NM_000460.4). computational analysis indicates that this mutation suppresses the binding of some essential transcription factors to the THPO promoter. Family segregation analysis shows a significant reduction in platelet counts among carriers of the mutation. Our patient received allogeneic haematopoietic stem cell transplantation (HSCT) from her HLA-matched sister (MSD), who carries the mutation. After allogeneic HSCT, the patient showed 100% full donor chimerism, but 1 year after HSCT, despite full donor chimerism, the patient did not complete recover from platelet count, and she has received romiplostim several times. Understanding the MPL-THPO pathway is vital for managing CAMT, emphasizing the importance of identifying and assessing patients' mutations for tailored treatment.

RNA modifications play a crucial role in regulating gene expression, splicing, decoding, translation, and degradation. Among the most studied modifications are adenosine-to-inosine (A-to-I) RNA editing and N⁶-methyladenosine (m⁶A). While m⁶A is reversible, enabling dynamic regulation of gene expression; A-to-I editing is irreversible, leading to permanent changes in RNA sequences. This raises a thought-provoking question: why do different RNA modifications have such distinct reversibility? Is this feature random or governed by evolutionary constraints? We interrogate the mechanistic (proximate cause) and evolutionary (ultimate cause) reasons for how and why inosine cannot be reversed by adding an amino group but m⁶A remains reversible, despite both modifications have the option to be degraded along with host RNAs. We also discuss whether inosine can have reader proteins like m⁶A to exert dynamic and regulatory control. Finally, we explore the evolutionary significance of these differences and their implications for future research in RNA modifications.