Characteristics of pseudogene degeneration at the coding level are well-known, such as a shift toward neutral rates of nonsynonymous substitutions and gain of frameshift mutations. In contrast, degeneration of pseudogene transcriptional regulation is not well understood. Here, we test two predictions of regulatory degeneration along a pseudogenized lineage: 1) Decreased transcription factor (TF) binding and 2) accelerated evolution in putative cis-regulatory regions.We find evidence for decreased TF binding levels nearby two primate pseudogenes compared with functional liver genes. However, the majority of TF-bound sequences nearby pseudogenes do not show evidence for lineage-specific accelerated rates of evolution. We conclude that decreases in TF binding level could be a marker for regulatory degeneration, while sequence degeneration in primate cis-regulatory modules may be obscured by background rates of TF binding site turnover.
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http://dx.doi.org/10.1093/molbev/msw030 | DOI Listing |
J Genet Genomics
January 2025
Department of Medical Genetics and Center for Rare Diseases, the Second Affiliated Hospital of Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation, Hangzhou, Zhejiang 310009, China; Nanhu Brain-computer Interface Institute, Hangzhou, Zhejiang 311100, China; MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310012, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai 200031, China; Lead contact. Electronic address:
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.
View Article and Find Full Text PDFMol Cell Probes
January 2025
Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland, Mittlere Strasse 91, CH-4031. Electronic address:
The rapid advancements in the field of genetics have significantly propelled the development of gene therapies, paving the way for innovative treatments of various hereditary disorders. This review focuses on the genetics of ophthalmologic conditions, highlighting the currently approved ophthalmic gene therapy and exploring emerging therapeutic strategies under development. Inherited retinal dystrophies represent a heterogeneous group of genetic disorders that manifest across a broad spectrum from infancy to late middle age.
View Article and Find Full Text PDFJ Inflamm Res
January 2025
Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Background: Osteoarthritis (OA) is a leading cause of pain, disability, and reduced mobility worldwide, characterized by metabolic imbalances in chondrocytes, extracellular matrix (ECM), and subchondral bone. Emerging evidence highlights the critical role of long non-coding RNAs (lncRNAs) in OA pathogenesis. This study focuses on lncRNA PTS-1, a novel lncRNA, to explore its function and regulatory mechanisms in OA progression.
View Article and Find Full Text PDFJ Transl Med
January 2025
Division of Spine, Department of Orthopedics, Tongji Hospital affiliated to Tongji University, Tongji University School of Medicine, Shanghai, 200065, China.
Background: Ferroptosis and immune responses are critical pathological events in spinal cord injury (SCI), whereas relative molecular and cellular mechanisms remain unclear.
Methods: Micro-array datasets (GSE45006, GSE69334), RNA sequencing (RNA-seq) dataset (GSE151371), spatial transcriptome datasets (GSE214349, GSE184369), and single cell RNA sequencing (scRNA-seq) datasets (GSE162610, GSE226286) were available from the Gene Expression Omnibus (GEO) database. Through weighted gene co-expression network analysis and differential expression analysis in GSE45006, we identified differentially expressed time- and immune-related genes (DETIRGs) associated with chronic SCI and differentially expressed ferroptosis- and immune-related genes (DEFIRGs), which were validated in GSE151371.
Cell Rep
January 2025
Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA; Graduate Program in Cell and Molecular Biology, University of Michigan, Ann Arbor, MI, USA; Medical Scientist Training Program, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA. Electronic address:
The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation.
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