Genomes encode for genes and non-coding DNA, both capable of transcriptional activity. However, unlike canonical genes, many transcripts from non-coding DNA have limited evidence of conservation or function. Here, to determine how much biological noise is expected from non-genic sequences, we quantify the regulatory activity of evolutionarily naive DNA using RNA-seq in yeast and computational predictions in humans. In yeast, more than 99% of naive DNA bases were transcribed. Unlike the evolved transcriptome, naive transcripts frequently overlapped with opposite sense transcripts, suggesting selection favored coherent gene structures in the yeast genome. In humans, regulation-associated chromatin activity is predicted to be common in naive dinucleotide-content-matched randomized DNA. Here, naive and evolved DNA have similar co-occurrence and cell-type specificity of chromatin marks, challenging these as indicators of selection. However, in both yeast and humans, extreme high activities were rare in naive DNA, suggesting they result from selection. Overall, basal regulatory activity seems to be the default, which selection can hone to evolve a function or, if detrimental, repress.

基因组编码基因和非编码 DNA，两者都具有转录活性。然而，与规范基因不同，许多非编码 DNA 的转录物的保守性或功能证据有限。在这里，为了确定非基因序列预期有多少生物噪音，我们使用酵母中的 RNA-seq 和人类中的计算预测来量化进化上原始 DNA 的调控活动。在酵母中，超过 99% 的原始 DNA 碱基都被转录。与进化的转录组不同，原始转录本经常与相反意义的转录本重叠，这表明选择有利于酵母基因组中的连贯基因结构。在人类中，与调节相关的染色质活性预计在原始二核苷酸含量匹配的随机 DNA 中很常见。在这里，幼稚和进化的 DNA 具有相似的共现性和染色质标记的细胞类型特异性，对这些作为选择指标提出了挑战。然而，在酵母和人类中，原始 DNA 中很少有极高的活性，这表明它们是选择的结果。总体而言，基础调节活动似乎是默认的，选择可以磨练其进化功能，或者如果有害，则可以抑制。