几十年来,众所周知,人类DNA中大量的基因表现出重叠;然而,这些重叠的生物学和进化意义仍然知之甚少。这项研究的重点是调查重叠的特定情况,其中重叠的DNA区域包含蛋白质编码基因的编码DNA序列(CDS)。结果表明,重叠CDS编码的蛋白质比非重叠CDS编码的蛋白质表现出更大的紊乱。此外,这些DNA区域被鉴定为富含GC。这可以部分归因于来自两个不同阅读框而不是一个阅读框的终止密码子的缺失。此外,发现这些区域的单核苷酸多态性(SNP)位点较少,可能是由于重叠状态引起的限制,其中突变可能同时影响两个基因。在阐明这些属性的同时,NR1D1-THRA基因对是一种特殊情况,具有高度结构化的蛋白质,并且在整个欧洲哺乳动物中具有明显保守的序列。NR1D1和THRA都是在其C端缺乏配体结合域的核受体,这是这些基因对重叠的区域。NR1D1基因参与昼夜节律的调节,虽然THRA基因编码甲状腺激素受体,两者都在各种生理过程中起着至关重要的作用。这项研究表明,除了他们既定的功能之外,这些基因的特殊重叠的CDS区域可能编码额外的蛋白质片段,但未被发现,生物学角色。
For several decades, it has been known that a substantial number of genes within human DNA exhibit overlap; however, the biological and evolutionary significance of these overlaps remain poorly understood. This study focused on investigating specific instances of overlap where the overlapping DNA region encompasses the coding DNA sequences (CDSs) of protein-coding genes. The results revealed that proteins encoded by overlapping CDSs exhibit greater disorder than those from nonoverlapping CDSs. Additionally, these DNA regions were identified as GC-rich. This could be partially attributed to the absence of stop codons from two distinct reading frames rather than one. Furthermore, these regions were found to harbour fewer single-nucleotide polymorphism (SNP) sites, possibly due to constraints arising from the overlapping state where mutations could affect two genes simultaneously.While elucidating these properties, the NR1D1-THRA gene pair emerged as an exceptional
case with highly structured proteins and a distinctly conserved sequence across eutherian mammals. Both NR1D1 and THRA are nuclear receptors lacking a ligand-binding domain at their C-terminus, which is the region where these gene pairs overlap. The NR1D1 gene is involved in the regulation of circadian rhythm, while the THRA gene encodes a thyroid hormone receptor, and both play crucial roles in various physiological processes. This study suggests that, in addition to their well-established functions, the specifically overlapping CDS regions of these genes may encode protein segments with additional, yet undiscovered, biological roles.