对6515个外体的分析揭示了大多数人类蛋白质编码变体的最近起源
Wenqing Fu1, Timothy D O'Connor, Goo Jun
1Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. wqfu@u.washington.edu
Nature
|December 4, 2012
概括
大多数人类蛋白质编码突变是最近出现的,在过去的1万年内. 疾病基因不成比例地携带更年轻,有害的单核酸变体 (SNV),影响人类进化和疾病基因发现.
科学领域:
- 人类进化遗传学 人类进化遗传学
- 人口遗传学 人口遗传学
- 基因组学就是基因组学.
背景情况:
- 了解人类进化历史需要对基因突变进行约会.
- 最近的人口增长表明,许多突变在进化上是年轻的.
- 识别突变年龄有助于发现疾病基因.
研究的目的:
- 量化评估人类群体中突变的年龄分布.
- 调查最近人类历史对遗传变异的影响.
- 为疾病基因发现提供洞察力.
主要方法:
- 在6515个个体中重新测序了15336个基因.
- 对于1,146,401个自体单核酸变体 (SNVs) 的年龄推断.
- 跨祖先群体和基因类型的变异年龄和频率的比较.
主要成果:
- 大约73%的编码蛋白质的SNV和86%的有害SNV在过去的5000至1万年中出现.
- 与其他基因相比,有害的SNV在疾病基因中平均更年轻.
- 与非洲裔美国人相比,欧洲裔美国人在关键基因中显示出过多的有害变异.
结论:
- 最近的人类历史显著塑造了当前有害SNVs的负担.
- 突变年龄是理解人类遗传变异和疾病的关键因素.
- 这些发现为在疾病基因发现工作中优先考虑变异提供了实际指导.
相关概念视频
Exon 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...
Organization of Genes
Overview
Gene Evolution - Fast or Slow?
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
Gene Evolution - Fast or Slow?
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
Genome Size and the Evolution of New Genes
While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.
Genome Size and the Evolution of New Genes
While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.


