Proteins that emerge de novo from noncoding DNA could negatively or positively influence cellular physiology in the sense of providing a possible adaptive advantage. Here, we employ two approaches to study such effects in a human cell line by expressing random sequences and mouse de novo genes that lack homologs in the human genome. We show that both approaches lead to differential growth effects of the cell clones dependent on the sequences they express. For the random sequences, 53% of the clones decreased in frequency, and about 8% increased in frequency in a joint growth experiment. Of the 14 mouse de novo genes tested in a similar joint growth experiment, 10 decreased, and 3 increased in frequency. When individually analysed, each mouse de novo gene triggers a unique transcriptomic response in the human cells, indicating mostly specific rather than generalized effects. Structural analysis of the de novo gene open reading frames (ORFs) reveals a range of intrinsic disorder scores and/or foldability into alpha-helices or beta sheets, but these do not correlate with their effects on the growth of the cells. Our results indicate that de novo evolved ORFs could easily become integrated into cellular regulatory pathways, since most interact with components of these pathways and could therefore become directly subject to positive selection if the general conditions allow this.
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http://dx.doi.org/10.1093/gbe/evae175 | DOI Listing |
Medicine (Baltimore)
January 2025
Department of Urology, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian, China.
Previous studies have suggested an association between autoimmune diseases (AIDs) and the risk of prostate cancer (PCa). However, the causal relationship between AID and PCa remained unclear. The purpose of this study was to investigate the causal association between 3 common AIDs, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS), and the risk of PCa.
View Article and Find Full Text PDFFASEB J
January 2025
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.
Inflammatory bowel disease (IBD) with the two predominant endophenotypes-Crohn's disease (CD) and ulcerative colitis (UC)-represents a group of chronic gastrointestinal inflammatory conditions. Since most genetic associations with IBD are often limited to independent subtypes, we reported a genome-wide association study (GWAS) cross-trait analysis combined with CD and UC to enhance statistical power. Initially, we detected 256 association signals at 54 genomic susceptibility loci and further characterized the functionality of variants within these regions.
View Article and Find Full Text PDFBrain Behav
January 2025
Department of Neurology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China.
Background: The involvement of immune cells in the pathophysiology of intracerebral hemorrhage (ICH) is becoming increasingly recognized, yet their specific causal contributions remain uncertain. The objective of this research is to uncover the potential causal interactions between diverse immune cells and ICH using Mendelian randomization (MR) analysis.
Methods: Genetic variants associated with 731 immune cell traits were sourced from a comprehensive genome-wide association study (GWAS) involving 3757 participants.
J Craniofac Surg
January 2025
Department of Craniomaxillofacial Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
This meta-analysis compares the accuracy of mandible-first and maxilla-first approaches in bimaxillary orthognathic surgery to improve clinical decision-making. A systematic search was performed in PubMed, Web of Science, Embase, and Cochrane databases up to August 2024. The analysis included randomized controlled trials and cohort studies with a minimum of 10 patients.
View Article and Find Full Text PDFJMIR Form Res
January 2025
Limburg Clinical Research Center/Mobile Health Unit, Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
Background: Consumer-oriented wearable devices (CWDs) such as smartphones and smartwatches have gained prominence for their ability to detect atrial fibrillation (AF) through proprietary algorithms using electrocardiography or photoplethysmography (PPG)-based digital recordings. Despite numerous individual validation studies, a direct comparison of interdevice performance is lacking.
Objective: This study aimed to evaluate and compare the ability of CWDs to distinguish between sinus rhythm and AF.
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