Chen Chun-Hsi, Lin Hsuan-Yu, Pan Chia-Lin, Chen Feng-Chi
Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, 350 Taiwan.
BMC Res Notes. 2011 Aug 27;4:312. doi: 10.1186/1756-0500-4-312.
Organismal complexity is suggested to increase with the complexity of transcriptional and translational regulations. Supporting this notion is a recent study that demonstrated a higher level of tissue-specific gene expression in human than in mouse. However, whether this correlation can be extended beyond mammals remains unclear. In addition, 5' untranslated regions (5'UTRs), which have undergone stochastic elongation during evolution and potentially included an increased number of regulatory elements, may have played an important role in the emergence of organismal complexity. Although the lack of correlation between 5'UTR length and organismal complexity has been proposed, the underlying mechanisms remain unexplored.
In this study, we select the number of cell types as the measurement of organismal complexity and examine the correlation between (1) organismal complexity and transcriptional regulatory complexity; and (2) organismal complexity and 5'UTR length by comparing the 5'UTRs and multiple-tissue expression profiles of human (Homo sapiens), mouse (Mus musculus), and fruit fly (Drosophila melanogaster). The transcriptional regulatory complexity is measured by using the tissue specificity of gene expression and the ratio of non-constitutively expressed to constitutively expressed genes. We demonstrate that, whereas correlation (1) holds well in the three-way comparison, correlation (2) is not true. Results from a larger dataset that includes more than 15 species, ranging from yeast to human, also reject correlation (2). The reason for the failure of correlation (2) may be ascribed to: Firstly, longer 5'UTRs do not contribute to increased tissue specificity of gene expression. Secondly, the increased numbers of common translational regulatory elements in longer 5'UTRs do not lead to increased organismal complexity.
Our study has extended the evidence base for the correlation between organismal complexity and transcriptional regulatory complexity from mammals to fruit fly, the representative model organism of invertebrates. Furthermore, our results suggest that the elongation of 5'UTRs alone can not lead to the increase in regulatory complexity or the emergence of organismal complexity.
有观点认为,生物复杂性会随着转录和翻译调控的复杂性增加而提高。最近一项研究支持了这一观点,该研究表明人类组织特异性基因表达水平高于小鼠。然而,这种相关性是否能扩展到哺乳动物以外的生物仍不清楚。此外,5'非翻译区(5'UTR)在进化过程中经历了随机延长,可能包含了更多的调控元件,这可能在生物复杂性的出现中发挥了重要作用。尽管有人提出5'UTR长度与生物复杂性之间缺乏相关性,但其潜在机制仍未得到探索。
在本研究中,我们选择细胞类型的数量作为生物复杂性的衡量指标,并通过比较人类(智人)、小鼠(小家鼠)和果蝇(黑腹果蝇)的5'UTR和多组织表达谱,研究了(1)生物复杂性与转录调控复杂性之间的相关性;以及(2)生物复杂性与5'UTR长度之间的相关性。转录调控复杂性通过基因表达的组织特异性以及非组成性表达基因与组成性表达基因的比例来衡量。我们证明,虽然相关性(1)在三方比较中成立,但相关性(2)并不成立。来自包含从酵母到人类等15种以上物种的更大数据集的结果也否定了相关性(2)。相关性(2)不成立的原因可能是:首先,较长的5'UTR不会导致基因表达的组织特异性增加。其次,较长5'UTR中常见翻译调控元件数量的增加不会导致生物复杂性增加。
我们的研究将生物复杂性与转录调控复杂性之间相关性的证据基础从哺乳动物扩展到了果蝇,果蝇是无脊椎动物的代表性模式生物。此外,我们的结果表明,仅5'UTR的延长不会导致调控复杂性的增加或生物复杂性的出现。