下罗斯楼梯,或者如何选择更少的重组热点维持它们的存在
Zachary Baker1,2, Molly Przeworski1,2,3, Guy Sella2,3
1Department of Systems Biology, Columbia University, New York, United States.
eLife
|October 13, 2023
概括
PRDM9蛋白的快速演变是由于需要恢复对称结合,以便在半分裂过程中有效修复双链断裂 (DSB). 这确保了适当的同源染色体配对和成功的繁殖.
科学领域:
- 遗传学 遗传学是一种遗传学.
- 进化生物学 进化生物学
- 分子生物学分子生物学
背景情况:
- 介质重组发生在热点,PRDM9蛋白的DNA结合特异性决定了人类和小鼠的双链断裂 (DSB) 位置.
- 在DNA相互作用的残留物中,PRDM9迅速进化,但此前这种进化的模型与最近的实验发现不一致.
研究的目的:
- 调查PRDM9快速演变的替代假设,重点关注恢复对称结合的必要性,以有效修复DSB.
- 模拟PRDM9的进化动态,将其结合性与种群遗传过程联系起来.
主要方法:
- 开发了PRDM9进化的第一原则模型,结合了绑定动力学和种群遗传学.
- 分析了PRDM9结合部位使用率,对称结合和进化周转率之间的关系.
主要成果:
- 失去强的PRDM9结合部位会导致较弱部位的使用增加,从而减少对称结合.
- 这种减少有利于新的PRDM9等位基因,这些等位基因重新建立了较小的一组强结位,推动了快速的进化周转.
- 新的PRDM9等位基因的优势在于限制有效结合部位的使用,而不是增加整体结合.
结论:
- 快速的PRDM9进化是由于需要保持有效的对称结合来维护DSB修复和同源配对的需求.
- 介质重组热点可能已经进化,以提高DSB修复效率和/或同类配对.
相关概念视频
Crossing Over
4.4K
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,...
4.4K
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
Gene Conversion
9.8K
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
9.8K
Homologous Recombination
50.6K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
50.6K
Mismatch Repair
4.9K
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...
4.9K
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


