Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Science. 2013 Dec 13;342(6164):1367-72. doi: 10.1126/science.1243490.
Genomes contain both a genetic code specifying amino acids and a regulatory code specifying transcription factor (TF) recognition sequences. We used genomic deoxyribonuclease I footprinting to map nucleotide resolution TF occupancy across the human exome in 81 diverse cell types. We found that ~15% of human codons are dual-use codons ("duons") that simultaneously specify both amino acids and TF recognition sites. Duons are highly conserved and have shaped protein evolution, and TF-imposed constraint appears to be a major driver of codon usage bias. Conversely, the regulatory code has been selectively depleted of TFs that recognize stop codons. More than 17% of single-nucleotide variants within duons directly alter TF binding. Pervasive dual encoding of amino acid and regulatory information appears to be a fundamental feature of genome evolution.
基因组既包含指定氨基酸的遗传密码，也包含指定转录因子（TF）识别序列的调控密码。我们使用基因组脱氧核糖核酸酶 I 足迹法在 81 种不同的细胞类型中绘制了人类外显子上核苷酸分辨率的 TF 占有率图谱。我们发现，大约 15%的人类密码子是双用途密码子（“duons”），它们同时指定了氨基酸和 TF 识别位点。Duons 高度保守，影响了蛋白质的进化，而 TF 施加的约束似乎是密码子使用偏好的主要驱动因素。相反，调控密码子中已经选择性地耗尽了识别终止密码子的 TF。Duons 内超过 17%的单核苷酸变异直接改变了 TF 的结合。氨基酸和调控信息的普遍双重编码似乎是基因组进化的一个基本特征。
