再组合使时间信号平滑,因为宿主内HIV基因的潜伏时间被破坏
Lauren A Castro1,2, Thomas Leitner3, Ethan Romero-Severson3
1Information Systems and Modeling, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Virus evolution
|July 3, 2023
概括
潜伏的HIV前病毒的重新激活会破坏进化信号,但再组合令人惊地恢复了它们. 这项研究模拟了宿主体内的HIV进化,以了解这些复杂的动态及其遗传学表征.
科学领域:
- 进化生物学 进化生物学
- 病毒学 病毒学
- 计算生物学 计算生物学
背景情况:
- 人类免疫缺陷病毒 (HIV) 在宿主内部的进化对由于病毒潜伏反应和重组而导致的基因重建提出了挑战.
- 暂病毒延迟可以破坏家族遗传树的时间信号,导致进化速率的变化.
- 重组复杂化艾滋病毒的动态,混合基因组和创造非二分化进化结构.
研究的目的:
- 开发一种基于凝聚的模拟器,用于宿主内部的HIV进化,包括延迟,重组和种群大小动态.
- 为了研究真正复杂的家谱 (祖先重组图 - ARG) 和观察到的家族遗传树之间的关系.
- 了解延迟和重组如何影响家族遗传信号及其可恢复性.
主要方法:
- 开发了一个基于凝聚的模拟器模型,在宿主HIV进化中建模,包括延迟,重组和有效的人口规模.
- 将ARG分解为独特的站点树来计算距离矩阵和相应的分叉树,以与标准的族系进行比较.
- 采用近似贝叶斯计算与统计探测器来调整模拟模型与九个纵向采样在宿主内艾滋病毒基因.
主要成果:
- 值得注意的是,重组发现可以通过重新引入较旧的潜在基因组的碎片来恢复因延迟中断的时间信号.
- 重组实际上是对现有异质性的平均值,无论是来自混合时间信号还是人口瓶.
- 延迟和重组的信号可以在标准的家族遗传树中观察到,尽管这些树是真正的进化历史的不完美表现.
结论:
- 开发的模拟系统提供了一个工具,用于调查潜伏,重组和人群规模瓶在宿主HIV进化中的复杂相互作用.
- 在面对延迟诱导的干扰时,重组在维持基因信号方面发挥着至关重要的作用.
- 这项研究表明,标准的遗传学方法仍然可以揭示复杂进化过程的信号,如延迟和重组.
相关概念视频
Viral Recombination
23.5K
Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
23.5K
Size and Structure of Viral Genomes
65
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
65
Conservative Site-specific Recombination and Phase Variation
6.0K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.0K
Crossing Over
4.5K
Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I,...
4.5K
Retrovirus Life Cycles
46.2K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
46.2K
Homologous Recombination
4.7K
4.7K


