黑腹果蝇常染色体基因朱砂隐性可见突变的基因内 DNA 变化的剂量、LET 和基因依赖模式

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2025-02-26 DOI:10.1016/j.mrgentox.2025.503857

I.D. Alexandrov, M.V. Alexandrova, K.P. Afanasyeva, N.E. Kharchenko

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引用次数: 0

摘要

对2个自发、26个γ射线-和10个中子/中子+ γ射线诱导的cn基因/点突变体进行了序列分析。一个自发突变体研究了整个母系序列（4644 bp，完全基因转换）。第二个突变体包含DNA变化簇，包括部分基因转换（束长度为1087 bp），以及扩展缺失（47 bp）和外显子2的一个单碱基替换。在γ射线和中子/中子+ γ射线诱导的cn突变体中，几乎相同的DNA变化谱使它们有可能被归为一组36个辐射诱导的突变体。在研究的36个突变体中，5个（13.9%）突变体在cn基因组区研究序列内没有任何DNA变化。剩下的31个突变体包含36个DNA变化。有3个（8.3%）单碱基替换，2个（5.5%）长1 - 3 bp的帧移或索引，14个（38.9%）长度为5-21 bp的扩展缺失，12个（33.3%）基因转换事件，2个（5.5%）来源不明的大插入（~ 6.0 kb）， 1个（2.8%）大缺失（640 bp）， 1个（2.8%）扩展插入（8 bp）， 1个（2.8%）插入/重复（505 bp）。在12个基因转化事件中，完全转化事件7个，部分转化事件5个。部分转化的突变体的束长度为44 ~ 2247 bp。根据文献资料，基因转换、延长缺失和插入等DNA变化，必须分别是同源重组、单链退火和非同源末端加入修复途径的产物。我们提出DNA变化的初始DNA损伤是不同类型的DNA双链断裂（DSB）：(i)复杂的DSB，（ii）不太复杂的DSB，和（iii）简单的DSB。将cn基因/点突变体的DNA变化谱与黑色突变体的DNA变化谱进行比较，值得注意的是，不同基因组区域的DNA变化比例可能不同。

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The dose-, LET-, and gene-dependent patterns of intragenic DNA changes underlying recessive visible mutations at the autosomal gene cinnabar of Drosophila melanogaster

Sequence analysis of 2 spontaneous, 26 γ-ray- and 10 neutron/neutron + γ-ray-induced cn gene/point mutants was performed. One spontaneous mutant had the entire maternal сn¹ sequence studied (4644 bp, full gene conversion). The second mutant contained cluster of DNA changes consisting of a partial gene conversion (tract length of 1087 bp), as well as an extended deletion (47 bp) and one single-base substitution in exon 2. Almost the same spectra of DNA changes in γ-ray- and neutron/neutron + γ-ray-induced cn mutants made it possible to unite them into one group of 36 radiation-induced mutants. Among the 36 mutants studied, 5 mutants (13.9 %) did’t have any DNA changes within the studied sequence of the cn genomic region. The 31 remaining mutants contained 36 DNA changes. There were 3 (8.3 %) single-base substitutions, 2 (5.5 %) frameshifts or indels 1–3-bp long, 14 (38.9 %) extended deletions of 5–21 bp in length, 12 (33.3 %) gene conversion events, 2 (5.5 %) large insertion (∼ 6.0 kb) of unidentified origin, and 1 (2.8 %) large (640 bp) deletion, 1 (2.8 %) extended insertion (8 bp), 1 (2.8 %) insertion/duplication (505 bp). Among 12 gene conversion events, there were 7 full and 5 partial events. The tract length in the mutants with partial conversion varies from 44 to 2247 bp. According to literature data such DNA changes as gene conversion, extended deletions, and indels must be the products of homologous recombination, single-strand annealing, and non-homologous ends joining repair pathways, respectively. We propose that the initial DNA lesions for DNA changes are different types of DNA double-strand breaks (DSB): (i) complex DSBs, (ii) less complex DSBs, and (iii) simple DSBs. Comparing the spectrum of DNA changes in the cn gene/point mutants with that in black one, it is important to note that the ratio of DNA changes in various genomic regions may be different.

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来源期刊

Mutation research. Genetic toxicology and environmental mutagenesis 生物-毒理学

CiteScore

3.80

自引率

5.30%

发文量

审稿时长

105 days

期刊介绍： Mutation Research - Genetic Toxicology and Environmental Mutagenesis (MRGTEM) publishes papers advancing knowledge in the field of genetic toxicology. Papers are welcomed in the following areas: New developments in genotoxicity testing of chemical agents (e.g. improvements in methodology of assay systems and interpretation of results). Alternatives to and refinement of the use of animals in genotoxicity testing. Nano-genotoxicology, the study of genotoxicity hazards and risks related to novel man-made nanomaterials. Studies of epigenetic changes in relation to genotoxic effects. The use of structure-activity relationships in predicting genotoxic effects. The isolation and chemical characterization of novel environmental mutagens. The measurement of genotoxic effects in human populations, when accompanied by quantitative measurements of environmental or occupational exposures. The application of novel technologies for assessing the hazard and risks associated with genotoxic substances (e.g. OMICS or other high-throughput approaches to genotoxicity testing). MRGTEM is now accepting submissions for a new section of the journal: Current Topics in Genotoxicity Testing, that will be dedicated to the discussion of current issues relating to design, interpretation and strategic use of genotoxicity tests. This section is envisaged to include discussions relating to the development of new international testing guidelines, but also to wider topics in the field. The evaluation of contrasting or opposing viewpoints is welcomed as long as the presentation is in accordance with the journal''s aims, scope, and policies.