Microsatellite loci (tandem repeats of short nucleotide motifs) are highly abundant in eukaryotic genomes and often used as genetic markers because they can exhibit variation both within and between populations. Although widely recognized for their mutability and utility, the mutation rates of microsatellites have only been empirically estimated in a few species, and have rarely been compared across genotypes and populations within a species. Here, we investigate the dynamics of microsatellite mutation over long- and short-time periods by quantifying the starting abundance and mutation rates for microsatellites for six different genotypes of Daphnia magna, an aquatic microcrustacean, collected from three populations (Finland, Germany, and Israel). Using whole-genome sequences of these six starting genotypes, descendent mutation accumulation (MA) lines, and large population controls (non-MA lines), we find each genotype exhibits a distinctive initial microsatellite profile which clusters according to the population-of-origin. During the period of MA, we observe motif-specific, highly variable, and rapid microsatellite mutation rates across genotypes of D. magna, the average of which is order of magnitude greater than the recently reported rate observed in a single genotype of the congener, Daphnia pulex. In our experiment, genotypes with more microsatellites starting out exhibit greater losses and those with fewer microsatellites starting out exhibit greater gains-a context-dependent mutation bias that has not been reported previously. We discuss how genotype-specific mutation rates and spectra, in conjunction with evolutionary forces, can shape both the differential accumulation of repeat content in the genome and the evolution of mutation rates.
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http://dx.doi.org/10.1093/molbev/msz118 | DOI Listing |
Nat Cancer
January 2025
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution to the sampling bias problem by analyzing multiregion whole-exome and RNA sequencing data for 450 tumor regions from 184 patients with lung adenocarcinoma in the TRACERx study.
View Article and Find Full Text PDFEur J Dent
January 2025
Department of Fundamental Dental Medical Science, Kulliyyah of Dentistry, International Islamic University Malaysia, Kuantan, Pahang, Malaysia.
Objective: Oral squamous cell carcinoma (OSCC) is the prevailing type of oral cancer, representing poor prognosis and elevated mortality rates. Major risk factors for OSCC include the use of tobacco products, alcohol consumption, betel quid chewing, and genetic mutation. is traditionally consumed by cancer patients to fight against tumor growth.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
January 2025
Department of Medical Science and Biotechnology, I-Shou University, Kaohsiung City 82445, Taiwan. Electronic address:
Head and neck squamous cell carcinoma (HNSCC) cells have a high p53 mutation rate, but there were rare reported about the p53 gain of function through the prion-like aggregated form in p53 mutated HNSCC cells. Thioflavin T (ThT) is used to stain prion-like proteins in cells. Previously, we found that ThT and p53 staining were co-localized in HNSCC cells (Detroit 562 cells) with homozygous p53 R175H mutation.
View Article and Find Full Text PDFForensic Sci Int Genet
January 2025
Forensic DNA Division, National Forensic Service, Wonju, South Korea. Electronic address:
Y-chromosomal short tandem repeats (Y-STRs) at rapidly mutating (RM) loci have been suggested as tools for differentiating paternally related males. RMplex is a recently developed system that incorporates 26 RM loci and four fast-mutating (FM) loci, targeting 44 male-specific loci. Here, we evaluated the RMplex by estimating Y-STR mutation rates and the overall differentiation rates for 542 Korean father-son pairs, as well as the genetic population values for 409 unrelated males.
View Article and Find Full Text PDFACS Synth Biol
January 2025
Laboratory of Synthetic Microbiology, School of Chemical Engineering & Technology, Tianjin University, Tianjin 300072, P. R. China.
The fusion expression of deoxyribonucleic acid (DNA) replication-related proteins with nucleotide deaminase enzymes promotes random mutations in bacterial genomes, thereby increasing genetic diversity among the population. Most previous studies have focused on cytosine deaminase, which produces only C → T mutations, significantly limiting the variety of mutation types. In this study, we developed a fusion expression system by combining DnaG (RNA primase) with adenine deaminase TadA-8e (DnaG-TadA) in , which is capable of rapidly introducing A → G mutations into the genome, resulting in a 664-fold increase in terms of mutation rate.
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