Journal of Genetics and Genomics

Prospects for synthetic biology in 21^st century agriculture

Xingyan Ye, Kezhen Qin, Alisdair R. Fernie, Youjun Zhang

2025, 52(8): 967-986. doi: 10.1016/j.jgg.2024.12.016

Abstract (15)

Abstract:
Plant synthetic biology has emerged as a transformative field in agriculture, offering innovative solutions to enhance food security, provide resilience to climate change, and transition to sustainable farming practices. By integrating advanced genetic tools, computational modeling, and systems biology, researchers can precisely modify plant genomes to enhance traits such as yield, stress tolerance, and nutrient use efficiency. The ability to design plants with specific characteristics tailored to diverse environmental conditions and agricultural needs holds great potential to address global food security challenges. Here, we highlight recent advancements and applications of plant synthetic biology in agriculture, focusing on key areas such as photosynthetic efficiency, nitrogen fixation, drought tolerance, pathogen resistance, nutrient use efficiency, biofortification, climate resilience, microbiology engineering, synthetic plant genomes, and the integration of artificial intelligence with synthetic biology. These innovations aim to maximize resource use efficiency, reduce reliance on external inputs, and mitigate environmental impacts associated with conventional agricultural practices. Despite challenges related to regulatory approval and public acceptance, the integration of synthetic biology in agriculture holds immense promise for creating more resilient and sustainable agricultural systems, contributing to global food security and environmental sustainability. Rigorous multi-field testing of these approaches will undoubtedly be required to ensure reproducibility.

Unlocking the small RNAs: local and systemic modulators for advancing agronomic enhancement

Wenqi Ouyang, Hongda Sun, Yuan Wang

2025, 52(8): 987-1000. doi: 10.1016/j.jgg.2024.12.011

Abstract (20)

Abstract:
Small regulatory RNAs (sRNAs) are essential regulators of gene expression across a wide range of organisms to precisely modulate gene activity based on sequence-specific recognition. In model plants like Arabidopsis thaliana, extensive research has primarily concentrated on 21- to 24-nucleotide (nt) sRNAs, particularly microRNAs (miRNAs). Recent advancements in cell and tissue isolation techniques, coupled with advanced sequencing technologies, are revealing a diverse array of preciously uncharacterized sRNA species. These include structural RNA fragments as well as numerous cell- and tissue-specific sRNAs that are active during distinct developmental stages, thereby enhancing our understanding of the precise and dynamic regulatory roles of sRNAs in plant development regulation. Additionally, a notable feature of sRNAs is their capacity for amplification and movement between cells and tissues, which facilitates long-distance communication—an adaptation critical to plants due to their sessile nature. In this review, we will discuss the classification and mechanisms of sRNAs action, using legumes as a primary example due to their essential engagement for the unique organ establishment of root nodules and long-distance signaling, and further illustrating the potential applications of sRNAs in modern agricultural breeding and environmentally sustainable plant protection strategies.

Genomic insights into the genetic diversity, lateral gaits and high-altitude adaptation of Chakouyi (CKY) horses

Yang-Kai Liu, Wei-Wei Fu, Zhong-Yu Wang, Sheng-Wei Pei, Kai-Hui Li, Wei-Wei Wu, Meng-Zhen Le, Xiang-Peng Yue

2025, 52(8): 1001-1010. doi: 10.1016/j.jgg.2024.11.008

Abstract (17)

Abstract:
Chakouyi (CKY) horses from the Qinghai‒Xizang Plateau are well known for their unique lateral gaits and high-altitude adaptation, but genetic mechanisms underlying these phenotypes remain unclear. This study presents a comparison of 60 newly resequenced genomes of gaited CKY horses with 139 public genomes from 19 horse breeds. Population structure analyses (admixture, PCA, and neighbor-joining tree) reveal a close genetic relationship between CKY and other highland breeds (Tibetan and Chaidamu horses). Compared with other Chinese breeds, CKY horses present reduced nucleotide diversity (θπ) and lower inbreeding (F_ROH coefficient), suggesting possible selective pressures. A key region on chromosome 23 (Chr23: 22.3–22.6 Mb) is associated with the lateral gaits and harbors a highly prevalent nonsense mutation (Chr 23:22,391,254 C>A, Ser301STOP) in the DMRT3 gene, with an 88% homozygosity rate, which is strongly correlated with the distinctive gait of CKY horses. Furthermore, selection signals reveal that the EPAS1 gene is related to high-altitude adaptation, and the CAT gene contributes to altitude resilience in CKY horses. These findings suggest that preserving genetic diversity is essential for maintaining the unique gaits and high-altitude adaptations of CKY horses.

Uncovering the chromatin-mediated transcriptional regulatory network governing cold stress responses in fish immune cells

He Jiao, Songqian Huang, Minghao Zhang, Qiao Huang, Chenyu Yan, Jingting Qi, Jiangbo Cheng, Yuan Xu, Xue Zhai, Xinwen Li, Siyao Zhan, Wei Li, Zhichao Wu, Jiulin Chan, Liangbiao Chen, Peng Hu

2025, 52(8): 1046-1057. doi: 10.1016/j.jgg.2025.01.008

Abstract (12)

Abstract:
Temperature fluctuations challenge ectothermic species, particularly tropical fish dependent on external temperatures for physiological regulation. However, the molecular mechanisms through which low-temperature stress impacts immune responses in these species, especially in relation to chromatin accessibility and epigenetic regulation, remain poorly understood. In this study, we investigate chromatin and transcriptional changes in the head kidney and thymus tissues of Nile tilapia (Oreochromis niloticus), a tropical fish of significant economic importance, under cold stress. By analyzing cis-regulatory elements in open chromatin regions and their associated transcription factors (TFs), we construct a comprehensive transcriptional regulatory network (TRN) governing immune responses, including DNA damage-induced apoptosis. Our analysis identifies 119 TFs within the TRN, with Stat1 emerging as a central hub exhibiting distinct binding dynamics under cold stress, as revealed by footprint analysis. Overexpression of Stat1 in immune cells leads to apoptosis and increases the expression of apoptosis-related genes, many of which contain Stat1-binding sites in their regulatory regions, emphasizing its critical role in immune cell survival during cold stress. These results provide insights into the transcriptional and epigenetic regulation of immune responses to cold stress in tilapia and highlight Stat1 as a promising target for enhancing cold tolerance in tropical fish species.

S-sulfenylation-mediated inhibition of the GSNOR1 activity regulates ovule development in Arabidopsis

Shina Sun, Peng-Fei Jia, Wan Wang, Lichao Chen, Xinru Gong, Huifang Lin, Rong Wu, Wei-Cai Yang, Hong-Ju Li, Jianru Zuo, Hongyan Guo

2025, 52(8): 1034-1045. doi: 10.1016/j.jgg.2025.01.007

Abstract (4)

Abstract:
Reactive oxygen species (ROS) and nitric oxide (NO) are two critical classes of signaling molecules that regulate plant development and stress responses. The intracellular level of S-nitrosoglutathione (GSNO), a major bioactive NO species, is regulated by the highly conserved GSNO reductase (GSNOR). However, the molecular mechanisms underlying ROS-mediated regulation of GSNOR remain largely unclear. Here, we show that H₂O₂ negatively regulates the activity of GSNOR1 during ovule development in Arabidopsis. S-sulfenylation of GSNOR1 at Cys-284 inhibits its enzymatic activity. A GSNOR1^C284S mutation causes a reduction of the total SNO level in pistils, thereby disrupting NO homeostasis and eventually leading to defective ovule development. These findings illustrate a unique mechanism by which ROS regulates ovule development through S-sulfenylation-mediated inhibition of the GSNOR activity, thereby establishing a molecular link between ROS and NO signaling pathways in reproductive development.

Biallelic variants in SREBF2 cause autosomal recessive spastic paraplegia

Qiao Wei, Wenlu Fan, Hong-Fu Li, Pei-Shan Wang, Man Xu, Hai-Lin Dong, Hao Yu, Jialan Lyu, Wen-Jiao Luo, Dian-Fu Chen, Wanzhong Ge, Zhi-Ying Wu

2025, 52(8): 1021-1033. doi: 10.1016/j.jgg.2025.01.004

Abstract (10)

Abstract:
Hereditary spastic paraplegias (HSPs) refer to a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by the degeneration of motor neurons. To date, a significant number of patients still have not received a definite genetic diagnosis. Therefore, identifying unreported causative genes continues to be of great importance. Here, we perform whole-exome sequencing in a cohort of Chinese HSP patients. Three homozygous variants (p.L604W, p.S517F, and p.T984A) within the sterol regulatory element-binding factor 2 (SREBF2) gene are identified in one autosomal recessive family and two sporadic patients, respectively. Co-segregation is confirmed by Sanger sequencing in all available members. The three variants are rare in the public or in-house database and are predicted to be damaging. The biological impacts of variants in SREBF2 are examined by functional experiments in patient-derived fibroblasts and Drosophila. We find that the variants upregulate cellular cholesterol due to the overactivation of SREBP2, eventually impairing the autophagosomal and lysosomal functions. The overexpression of the mature form of SREBP2 leads to locomotion defects in Drosophila. Our findings identify SREBF2 as a causative gene for HSP and highlight the impairment of cholesterol as a critical pathway for HSP.

Vitamin D receptor regulates methyltransferase like 14 to mitigate colitis-associated colorectal cancer

Zheng Wang, Lingjuan Jiang, Xiaoyin Bai, Mingyue Guo, Runing Zhou, Qingyang Zhou, Hong Yang, Jiaming Qian

2025, 52(8): 1011-1020. doi: 10.1016/j.jgg.2024.12.020

Abstract (23)

Abstract:
Colitis-associated colorectal cancer (CAC), a serious complication of ulcerative colitis (UC), is associated with a poor prognosis. The vitamin D receptor (VDR) is recognized for its protective role in UC and CAC through the maintenance of intestinal barrier integrity and the regulation of inflammation. This study demonstrates a significant reduction in m⁶A-related genes, particularly methyltransferase like 14 (METTL14), in UC and CAC patients and identifies an association between METTL14 and VDR. In the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced mouse model, vitamin D treatment increases METTL14 expression and reduces tumor burden, while Vdr-knockout mice exhibit lower METTL14 levels and increased tumorigenesis. In vitro, the VDR agonist calcipotriol upregulates METTL14 in NCM460 cells, with this effect attenuated by VDR knockdown. VDR knockdown in DLD-1 colon cancer cells decreases METTL14 expression and promotes proliferation, which is reversed by METTL14 overexpression. Mechanistic studies reveal that VDR regulates METTL14 expression via promoter binding, modulating key target genes such as SOX4, DROSH, and PHLPP2. This study highlights the role of the VDR–METTL14 axis as a protective mechanism in CAC and suggests its potential as a therapeutic target for preventing and treating CAC.

Erratum to “GenomeSyn: a bioinformatics tool for visualizing genome synteny and structural variations” [J. Genet. Genom. (2022) 49, 1174–1176]