对XBB.1.5和BQ.1.1的深度突变扫描显示,在SARS-CoV-2进化过程中,正在进行的表观性漂移
Ashley L Taylor1, Tyler N Starr1
1Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
PLoS pathogens
|December 29, 2023
概括
由于表皮病,SARS-CoV-2的演变继续发生转变,影响像Omicron这样的病毒变体. 正在进行的深度突变扫描显示了尖端受体结合域 (RBD) 中被容忍的突变和删除,指导了未来的病毒进化.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 进化生物学 进化生物学
背景情况:
- 突变相互作用的表观症 (epistasis) 显著影响SARS-CoV-2的进化,正如Omicron变种的出现所示.
- 了解正在进行的表观变化对于预测SARS-CoV-2 (严重急性呼吸系统综合征冠状病毒2) 演变的轨迹至关重要.
研究的目的:
- 调查最近的SARS-CoV-2变种 (BQ.1.1,XBB.1.5) 尖端受体结合域 (RBD) 中的突变和缺失对ACE2结合和蛋白质表达的影响.
- 将当前的突变模式与早期的病毒菌株进行比较,以确定正在进行的表皮性漂移.
主要方法:
- 对SARS-CoV-2变种BQ.1.1和XBB.1.5.5进行了深度突变扫描.
- 评估了尖端RBD中所有单氨基酸替代和单共删除对ACE2结合亲和力和蛋白质表达的影响.
- 结果与之前分析的病毒株进行了比较.
主要成果:
- 发现许多突变可以耐受或增强ACE2受体结合.
- 网站对单个codon删除的耐受性通常与对氨基酸突变的耐受性保持一致.
- 确定正在进行的表皮病漂移,包括R493Q逆转和453,455和456位置的突变之间的相互作用,例如EG.5血统中的F456L.
结论:
- 最近的SARS-CoV-2替代物并没有像N501Y那样引起剧烈的表皮性转移,但表皮性漂移仍然存在.
- 在RBD中观察到被容忍的删除,包括BA.2.86中的Δ483,这表明可能存在indel变异.
- 突发性漂移继续塑造SARS-CoV-2的进化,可能将其引导到新的序列空间.
相关概念视频
Single Nucleotide Polymorphisms-SNPs
15.1K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.1K
Evolutionary Relationships through Genome Comparisons
5.7K
Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...
5.7K
Incomplete Dominance
22.6K
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
22.6K
Genetic Screens
5.0K
Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
5.0K
Gene Duplication and Divergence
6.1K
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...
6.1K
Exon Recombination
3.6K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...
Exon shuffling follows “splice frame rules.” Each exon...
3.6K


