Structure and expression pattern of Oct4 gene are conserved in vole Microtus rossiaemeridionalis

<p>Abstract</p> <p>Background</p> <p>Oct4 is a POU-domain transcriptional factor which is essential for maintaining pluripotency in several mammalian species. The mouse, human, and bovine <it>Oct4 </it>orthologs display a high conservation of nucleotide sequence and genomic organization.</p> <p>Results</p> <p>Here we report an isolation of a common vole (<it>Microtus rossiaemeridionalis) Oct4 </it>ortholog. Organization and exon-intron structure of vole <it>Oct4 </it>gene are similar to the gene organization in other mammalian species. It consists of five exons and a regulatory region including the minimal promoter, proximal and distal enhancers. Promoter and regulatory regions of the vole <it>Oct4 </it>gene also display a high similarity to the corresponding regions of <it>Oct4 </it>in other mammalian species, and are active during the transient transfection within luciferase reporter constructs into mouse P19 embryonic carcinoma cells and TG-2a embryonic stem cells. The vole <it>Oct4 </it>gene expression is detectable starting from the morula stage and until day 17 of embryonic development.</p> <p>Conclusion</p> <p>Genomic organization of this gene and its intron-exon structure in vole are identical to those in all previously studied species: it comprises five exons and the regulatory region containing several conserved elements. The activity of the <it>Oct4 </it>gene in vole, as well as in mouse, is confined only to pluripotent cells.</p

Negative Correlation between Expression Level and Evolutionary Rate of Long Intergenic Noncoding RNAs

Mammalian genomes contain numerous genes for long noncoding RNAs (lncRNAs). The functions of the lncRNAs remain largely unknown but their evolution appears to be constrained by purifying selection, albeit relatively weakly. To gain insights into the mode of evolution and the functional range of the lncRNA, they can be compared with much better characterized protein-coding genes. The evolutionary rate of the protein-coding genes shows a universal negative correlation with expression: highly expressed genes are on average more conserved during evolution than the genes with lower expression levels. This correlation was conceptualized in the misfolding-driven protein evolution hypothesis according to which misfolding is the principal cost incurred by protein expression. We sought to determine whether long intergenic ncRNAs (lincRNAs) follow the same evolutionary trend and indeed detected a moderate but statistically significant negative correlation between the evolutionary rate and expression level of human and mouse lincRNA genes. The magnitude of the correlation for the lincRNAs is similar to that for equal-sized sets of protein-coding genes with similar levels of sequence conservation. Additionally, the expression level of the lincRNAs is significantly and positively correlated with the predicted extent of lincRNA molecule folding (base-pairing), however, the contributions of evolutionary rates and folding to the expression level are independent. Thus, the anticorrelation between evolutionary rate and expression level appears to be a general feature of gene evolution that might be caused by similar deleterious effects of protein and RNA misfolding and/or other factors, for example, the number of interacting partners of the gene product

Characterization of the Genomic Xist Locus in Rodents Reveals Conservation of Overall Gene Structure and Tandem Repeats but Rapid Evolution of Unique Sequence

The Xist locus plays a central role in the regulation of X chromosome inactivation in mammals, although its exact mode of action remains to be elucidated. Evolutionary studies are important in identifying conserved genomic regions and defining their possible function. Here we report cloning, sequence analysis, and detailed characterization of the Xist gene from four closely related species of common vole (field mouse), Microtus arvalis. Our analysis reveals that there is overall conservation of Xist gene structure both between different vole species and relative to mouse and human Xist/XIST. Within transcribed sequence, there is significant conservation over five short regions of unique sequence and also over Xist-specific tandem repeats. The majority of unique sequences, however, are evolving at an unexpectedly high rate. This is also evident from analysis of flanking sequences, which reveals a very high rate of rearrangement and invasion of dispersed repeats. We discuss these results in the context of Xist gene function and evolution. [The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AJ310127–AJ310130 and AJ311670.