Dataset Information

Mutperiod: Analysis of periodic mutation rates in nucleosomes.

ABSTRACT: Nucleosomes modulate DNA damage and repair, resulting in periodic mutation rates in nucleosomal DNA. Previous research has characterized these patterns in many sequenced tumor genomes; however, computational tools to identify and quantify these periodicities have not been developed for the broader scientific community. Here, we describe mutperiod, a Python and R based toolset that quantifies nucleosome mutational periodicities and compares them across different genetic and cellular backgrounds. We use mutperiod to demonstrate that DNA mismatch repair contributes to the nucleosome mutational periodicity observed in esophageal adenocarcinomas, and that the strength of this mutational periodicity varies in different chromatin states.

SUBMITTER: Morledge-Hampton B

PROVIDER: S-EPMC8349767 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Mutperiod: Analysis of periodic mutation rates in nucleosomes.

Morledge-Hampton Benjamin B Wyrick John J JJ

Computational and structural biotechnology journal 20210726

Nucleosomes modulate DNA damage and repair, resulting in periodic mutation rates in nucleosomal DNA. Previous research has characterized these patterns in many sequenced tumor genomes; however, computational tools to identify and quantify these periodicities have not been developed for the broader scientific community. Here, we describe mutperiod, a Python and R based toolset that quantifies nucleosome mutational periodicities and compares them across different genetic and cellular backgrounds. ...[more]

PMID: 34527191

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Project description:The causes and consequences of spatiotemporal variation in mutation rates remain to be explored in nearly all organisms. Here we examine relationships between local mutation rates and replication timing in three bacterial species whose genomes have multiple chromosomes: Vibrio fischeri, Vibrio cholerae, and Burkholderia cenocepacia Following five mutation accumulation experiments with these bacteria conducted in the near absence of natural selection, the genomes of clones from each lineage were sequenced and analyzed to identify variation in mutation rates and spectra. In lineages lacking mismatch repair, base substitution mutation rates vary in a mirrored wave-like pattern on opposing replichores of the large chromosomes of V. fischeri and V. cholerae, where concurrently replicated regions experience similar base substitution mutation rates. The base substitution mutation rates on the small chromosome are less variable in both species but occur at similar rates to those in the concurrently replicated regions of the large chromosome. Neither nucleotide composition nor frequency of nucleotide motifs differed among regions experiencing high and low base substitution rates, which along with the inferred ~800-kb wave period suggests that the source of the periodicity is not sequence specific but rather a systematic process related to the cell cycle. These results support the notion that base substitution mutation rates are likely to vary systematically across many bacterial genomes, which exposes certain genes to elevated deleterious mutational load.IMPORTANCE That mutation rates vary within bacterial genomes is well known, but the detailed study of these biases has been made possible only recently with contemporary sequencing methods. We applied these methods to understand how bacterial genomes with multiple chromosomes, like those of Vibrio and Burkholderia, might experience heterogeneous mutation rates because of their unusual replication and the greater genetic diversity found on smaller chromosomes. This study captured thousands of mutations and revealed wave-like rate variation that is synchronized with replication timing and not explained by sequence context. The scale of this rate variation over hundreds of kilobases of DNA strongly suggests that a temporally regulated cellular process may generate wave-like variation in mutation risk. These findings add to our understanding of how mutation risk is distributed across bacterial and likely also eukaryotic genomes, owing to their highly conserved replication and repair machinery.

Project description:Rapidly mutating Y-STRs (RM Y-STRs) harbor great potential to distinguish male relatives and achieve male identification. However, forensic applications were greatly limited by the small number of the initially identified 14 RM Y-STRs. Recently, with the emergence of 12 novel RM Y-STRs, an integrated panel named RMplex was introduced, which contains all 26 RM Y-STRs and four fast mutating Y-STRs (FM Y-STRs). To obtain the first data on the mutation rates and father-son differentiation rates of the 30 newly proposed Y-STRs in Chinese populations, we performed an empirical mutation study on 307 DNA-confirmed Chinese paternal pairs. Previously reported mutation rates for 14 RM Y-STRs in Chinese and European populations were pooled and merged with our data. The highest meiosis number for the two groups reached 4771 and 2687, respectively. Five loci showed significant differences between the populations (DYS570, DYS399S1, DYS547, DYS612, and DYF403S1b). For the new panel covering 30 Y-STR loci, our results show extensive differences in the mutation rates between the two populations, as well. 10 RM Y-STR loci showed relatively low mutation rates (10-3-10-2 per meiosis) and 2 FM Y-STR loci had rapid mutation rates (> 10-2 per meiosis) in the Chinese population. Several-fold differences in mutation rates were found in nine Y-STR loci between the Chinese and reference populations, with two loci having significantly higher mutation rates and one locus with a significantly lower mutation rate in the Chinese population (P < 0.05). Eighteen RM Y-STRs (> 10-2 per meiosis), 8 FM Y-STR loci (5×10-3-10-2 per meiosis), 3 moderately mutating Y-STRs (MM Y-STRs, 10-3-5×10-3 per meiosis), and one locus with no observed mutation events were identified in the Chinese population. 40.06% of the Chinese paternity pairs were discriminated with RMplex while only 20.84% with the initial 14 RM Y-STRs, indicating that RMplex is beneficial for distinguishing paternally related males. Future studies on populations of different genetic backgrounds are necessary to obtain comprehensive estimates of mutation rates at these new loci.

Dataset Information

Mutperiod: Analysis of periodic mutation rates in nucleosomes.

Publications

Mutperiod: Analysis of periodic mutation rates in nucleosomes.

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