The plausible reason why the length of 5' untranslated region is unrelated to organismal complexity

BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.