更新的埃尔德曼揭示了串联重复副本号码是相变的,影响M. 结核病在整个进化时间尺度上的适应
Samuel J Modlin1, Nachiket Thosar1, Paulina M Mejía-Ponce1
1Laboratory for Pathogenesis of Clinical Drug Resistance and Persistence, School of Public Health, San Diego State University, San Diego, California, USA.
mSystems
|December 17, 2025
概括
高质量的Mycobacterium结核病参考基因组对于了解疾病至关重要. 超深度测序揭示了当前埃尔德曼菌株基因组中的错误,并确定了基因变异驱动适应的新机制.
科学领域:
- 基因组学就是基因组学.
- 微生物学 微生物学
- 进化生物学 进化生物学
背景情况:
- 高质量的参考基因组对于比较基因组学和Mycobacterium tuberculosis (Mtb) 中的基因型-表型映射至关重要.
- 目前的埃尔德曼参考基因组 (ErdmanSTJ) 含有不准确性,可能阻碍了Mtb研究.
研究的目的:
- 通过使用超深度HiFi测序来纠正和改进Mtb Erdman菌株参考基因组.
- 识别和描述结构变异 (SVs) 以及它们对Mtb进化和表型的影响.
主要方法:
- 超深度HiFi测序Mtb埃德曼菌株.
- 与现有的参考基因组相比,对小和结构变异的纠正.
- 对促进体双重重复制拷贝数变异 (CNVs) 和它们与基因功能相关性的分析.
主要成果:
- 修正后的ErdmanTI基因组揭示了ErdmanSTJ引用中的许多可能的错误.
- 确定了28种结构变异 (SV),其中一半可能是参考基因组中的错误.
- 在pe/ppe基因中发现了对框架内SVs的新奇偏差,以及促销者并列重复 (PTR) 的频繁的多细胞复制数变异 (CNVs).
- PTR CNV与表型的快速切换有关,包括氧化耐药性,生物膜形成,药物耐受性和糖利用.
结论:
- 超深度测序揭示了由PTR CNVs驱动的Mtb中常见的相变机制,此前被短读测序限制所掩盖.
- 这些发现为Mtb比较研究提供了改进的参考基因组,并揭示了适应性灵活性的重要机制.
- 该研究重构了Mtb的进化潜力,强调了由于测序限制和亚种群分辨率而低估的适应性灵活性.
相关概念视频
Mismatch Repair
6.2K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
6.2K
Mismatch Repair
43.4K
Overview
43.4K
Comparing Copy Number Variations and SNPs
18.5K
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
18.5K
Genome Copying Errors
5.0K
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
5.0K
Gene Duplication and Divergence
7.8K
The seminal work of Ohno in 1970 popularized the idea of gene duplication and divergence. DNA sequence comparison studies reveal that a large portion of the genes in bacteria, archaebacteria, and eukaryotes was generated by gene duplication and divergence, indicating its critical role in evolution.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...
7.8K
Gene Evolution - Fast or Slow?
7.9K
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
7.9K


