PRDM9は,ヒトとマウスのメオティック再結合ホットスポットの主要な決定因子です
Science (New York, N.Y.)
|January 2, 2010
まとめ
Prdm9遺伝子は,メオティック再結合ホットスポットを指定するために重要である. その亜鉛指のDNA結合配列は,再結合がどこで起こるかを決定し,哺乳類のゲノム全体に分布するための分子基盤を提供します.
科学分野:
- 遺伝学とゲノミクス
- 分子生物学は分子生物学である.
- 生殖生物学 生殖生物学
背景:
- 遺伝的多様性にとって不可欠なメオティック再結合は,ゲノム全体に均等に分布していない.
- 再結合イベントは,ホットスポットと呼ばれる特定のゲノム領域にクラスタリングすることが知られている.
- これらのホットスポットの正確な位置を決定する分子メカニズムは,まだ完全に理解されていません.
研究 の 目的:
- ミエオティック再結合ホットスポットの特定に起因する重要な遺伝的要因を特定する.
- 再結合ホットスポットの位置と使用を決定するPrdm9遺伝子の役割を明らかにする.
- 哺乳類における中間再結合の全ゲノム分布のための分子基礎を確立する.
主な方法:
- 異なるホットスポット利用のマウス株におけるPrdm9遺伝子亜鉛指DNA結合配列の比較分析.
- ヒトのPRDM9アレルのDNA結合特異性のインシリコ予測とインビトロ実験的検証.
- PRDM9亜鉛指アレル変異体とヒト集団における全ゲノムホットスポット使用パターンとの統計的関連性研究.
主要な成果:
- Prdm9遺伝子の亜鉛指DNA結合配列のポリモルフィズムは,マウスの異なるメオティック再結合ホットスポット使用パターンと相関しています.
- 人間のPRDM9タンパク質,特にその亜鉛指ドメインは,ヒトのホットスポットで濃縮された13メルのDNAモチーフを結合すると予測され,実験的に検証されています.
- 人間のPRDM9アレル変異は,ゲノム全体の再結合ホットスポット利用の変異と有意な関連性を示し,ヒト集団におけるその役割を強調しています.
結論:
- Prdm9遺伝子は,哺乳類におけるメオティック再結合ホットスポット特異性の主要な決定因子である.
- PRDM9のDNA結合特異性は,その亜鉛指配列によって媒介され,特定のゲノム部位に中間再結合の開始を指示します.
- これらの発見は,哺乳類のゲノム全体で観察された中性再結合の分布に対する基本的な分子説明を提供します.
関連する概念動画
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...