Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Chen CH

PROVIDER: S-EPMC3224463 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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

Chen Chun-Hsi CH Lin Hsuan-Yu HY Pan Chia-Lin CL Chen Feng-Chi FC

BMC research notes 20110827

<h4>Background</h4>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 numb ...[more]

PMID: 21871111

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Project description:Repeats in coding and non-coding regions have increasingly been associated with many human genetic disorders, such as Richieri-Costa-Pereira syndrome (RCPS). RCPS, mostly characterized by midline cleft mandible, Robin sequence and limb defects, is an autosomal-recessive acrofacial dysostosis mainly reported in Brazilian patients. This disorder is caused by decreased levels of EIF4A3, mostly due to an increased number of repeats at the EIF4A3 5'UTR. EIF4A3 5'UTR alleles are CG-rich and vary in size and organization of three types of motifs. An exclusive allelic pattern was identified among affected individuals, in which the CGCA-motif is the most prevalent, herein referred as "disease-associated CGCA-20nt motif." The origin of the pathogenic alleles containing the disease-associated motif, as well as the functional effects of the 5'UTR motifs on EIF4A3 expression, to date, are entirely unknown. Here, we characterized 43 different EIF4A3 5'UTR alleles in a cohort of 380 unaffected individuals. We identified eight heterozygous unaffected individuals harboring the disease-associated CGCA-20nt motif and our haplotype analyses indicate that there are more than one haplotype associated with RCPS. The combined analysis of number, motif organization and haplotypic diversity, as well as the observation of two apparently distinct haplotypes associated with the disease-associated CGCA-20nt motif, suggest that the RCPS alleles might have arisen from independent unequal crossing-over events between ancient alleles at least twice. Moreover, we have shown that the number and sequence of motifs in the 5'UTR region is associated with EIF4A3 repression, which is not mediated by CpG methylation. In conclusion, this study has shown that the large number of repeats in EIF4A3 does not represent a dynamic mutation and RCPS can arise in any population harboring alleles with the CGCA-20nt motif. We also provided further evidence that EIF4A3 5'UTR is a regulatory region and the size and sequence type of the repeats at 5'UTR may contribute to clinical variability in RCPS.

Dataset Information

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

Background

Results

Conclusions

Publications

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

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