在人类和小鼠中,PRDM9是介质重组热点的主要决定因素
Science (New York, N.Y.)
|January 2, 2010
概括
Prdm9基因对于指定介质重组热点至关重要. 它的指DNA结合阵列决定了重组的发生地点,为其在哺乳动物中的全基因组分布提供了分子基础.
科学领域:
- 遗传学和基因组学 在
- 分子生物学分子生物学
- 生殖生物学 生殖生物学
背景情况:
- 对于遗传多样性来说必不可少的 meiotic 重组,在整个基因组中分布不均.
- 已知重组事件聚集在特定的基因组区域,称为热点.
- 这些热点的精确局部化背后的分子机制仍然不完全理解.
研究的目的:
- 确定负责介质重组热点规范的关键遗传因素.
- 阐明Prdm9基因在确定重组热点的位置和使用中的作用.
- 在哺乳动物中建立基因组复合的全基因组分布的分子基础.
主要方法:
- 在不同热点使用的小鼠菌株中对Prdm9基因指DNA结合阵列进行比较分析.
- 在人类PRDM9等位基的DNA结合特异性的in silico预测和体外实验验证.
- 在人类群体中,PRDM9指等位基因变体与全基因组热点使用模式之间的统计关联研究.
主要成果:
- Prdm9基因的指DNA结合阵列中的多态性与小鼠中明显的介质重组热点使用模式相关.
- 人类的PRDM9蛋白质,特别是其指域,预测并经过实验验证,可以结合在人体热点上丰富的13-mer DNA基因.
- 人类PRDM9等位基因变异与全基因组重组热点使用的变异有显著的关联,突出显示了它在人类群体中的作用.
结论:
- Prdm9基因是哺乳动物中介性重组热点规范的主要决定因素.
- 通过其指阵列介导的PRDM9的DNA结合特异性,将中介性重组的启动引导到特定的基因组位置.
- 这些发现为通过哺乳动物基因组观察到的介质重组分布提供了基本的分子解释.
相关概念视频
01:30Crossing Over
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, duplicated...
02:53Conservative Site-specific Recombination and Phase Variation
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...
02:32Exon Recombination
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 has three reading...
Exon shuffling follows “splice frame rules.” Each exon has three reading...
02:08Gene Conversion
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...
02:31Homologous Recombination
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...
01:20Mismatch Repair
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...