Computational Genomics Group, Institute for Bioinnovation, Biomedical Sciences Research Center "Alexander Fleming", Vari, Greece.
School of Medicine, University of Crete, Heraklion, Greece.
Mol Biol Evol. 2023 Mar 4;40(3). doi: 10.1093/molbev/msad059.
Intergenic genomic regions have essential regulatory and structural roles that impose constraints on their sequences. But regions that do not currently encode proteins also carry the potential to do so in the future. De novo gene emergence, the evolution of novel genes out of previously noncoding sequences has now been established as a potent force for genomic novelty. Recently, it was shown that intergenic regions in the genome of Saccharomyces cerevisiae harbor pervasive cryptic potential to, if theoretically translated, form transmembrane domains (TM domains) more frequently than expected by chance given their nucleotide composition, a property that we refer to as TM-forming enrichment. The source and biological relevance of this property is unknown. Here, we expand the investigation into the TM-forming potential of intergenic regions to the entire Saccharomycotina budding yeast subphylum, in an effort to explain this property and understand its importance. We find pervasive but variable enrichment in TM-forming potential across the subphylum regardless of the composition and average size of intergenic regions. This cryptic property is evenly spread across the genome, cannot be explained by the hydrophobic content of the sequence, and does not appear to localize to regions containing regulatory motifs. This TM-forming enrichment specifically, and not the actual TM-forming potential, is associated, across genomes, with more TM domains in evolutionarily young genes. Our findings shed light on this newly discovered feature of yeast genomes and constitute a first step toward understanding its evolutionary importance.
基因间基因组区域具有重要的调节和结构作用，这对它们的序列施加了限制。但是，目前不编码蛋白质的区域也有可能在未来编码蛋白质。新基因的从头出现，即从以前的非编码序列中进化出新基因，现已被确立为基因组创新的强大力量。最近，已经证明酿酒酵母基因组中的基因间区域具有普遍的潜在能力，如果从理论上进行翻译，它们比根据其核苷酸组成偶然形成跨膜结构域（TM 结构域）的频率更高，我们将这种特性称为 TM 形成富集。这种特性的来源和生物学相关性尚不清楚。在这里，我们将基因间区域的 TM 形成潜力的研究扩展到整个 Saccharomycotina 出芽酵母亚门，以努力解释这种特性并理解其重要性。我们发现，无论基因间区域的组成和平均大小如何，整个亚门都存在普遍但可变的 TM 形成潜力富集。这种隐性特性均匀分布在整个基因组中，不能用序列的疏水性内容来解释，也似乎不定位在含有调节基序的区域。这种 TM 形成富集，而不是实际的 TM 形成潜力，与进化年轻基因中更多的 TM 结构域相关。我们的发现揭示了酵母基因组中这一新发现的特征，并为理解其进化重要性迈出了第一步。
