Distribution of miRNA genes in the pig genome

Background

Recent completion of swine genome may simplify the production of swine as a large biomedical model. Here we studied sequence and location of known swine miRNA genes, key regulators of protein-coding genes at the level of RNA, and compared them to human and mouse data to prioritize future molecular studies.

Results

Distribution of miRNA genes in pig genome shows no particular relation to different genomic features including protein coding genes - proportions of miRNA genes in intergenic regions, introns and exons roughly agree with the size of these regions in the pig genome. Our analyses indicate that host genes harbouring intragenic miRNAs are longer from other protein-coding genes, however, no important GO enrichment was found. Swine mature miRNAs show high sequence similarity to their human and mouse orthologues. Location of miRNA genes relative to protein-coding genes is also similar among studied species, however, there are differences in the precise position in particular intergenic regions and within particular hosts. The most prominent difference between pig and human miRNAs is a large group of pig-specific sequences (53% of swine miRNAs). We found no evidence that this group of evolutionary new pig miRNAs is different from old miRNAs genes with respect to genomic location except that they are less likely to be clustered.

Conclusions

There are differences in precise location of orthologues miRNA genes in particular intergenic regions and within particular hosts, and their meaning for coexpression with protein-coding genes deserves experimental studies. Functional studies of a large group of pig-specific sequences in future may reveal limits of the pig as a model organism to study human gene expression.

Electronic supplementary material

The online version of this article (doi:10.1186/s12863-015-0166-3) contains supplementary material, which is available to authorized users.     

Origin and evolution of human microRNAs from transposable elements

We sought to evaluate the extent of the contribution of transposable elements (TEs) to human microRNA (miRNA) genes along with the evolutionary dynamics of TE-derived human miRNAs. We found 55 experimentally characterized human miRNA genes that are derived from TEs, and these TE-derived miRNAs have the potential to regulate thousands of human genes. Sequence comparisons revealed that TE-derived human miRNAs are less conserved, on average, than non-TE-derived miRNAs. However, there are 18 TE-derived miRNAs that are relatively conserved, and 14 of these are related to the ancient L2 and MIR families. Comparison of miRNA vs. mRNA expression patterns for TE-derived miRNAs and their putative target genes showed numerous cases of anti-correlated expression that are consistent with regulation via mRNA degradation. In addition to the known human miRNAs that we show to be derived from TE sequences, we predict an additional 85 novel TE-derived miRNA genes. TE sequences are typically disregarded in genomic surveys for miRNA genes and target sites; this is a mistake. Our results indicate that TEs provide a natural mechanism for the origination miRNAs that can contribute to regulatory divergence between species as well as a rich source for the discovery of as yet unknown miRNA genes.     

microRNA complements in deuterostomes: origin and evolution of microRNAs

SUMMARY Although numerous studies have emphasized the role of microRNAs (miRNAs) in the control of many different cellular processes, they might also exert a profound effect on the macroevolution of animal body plans. It has been hypothesized that, because miRNAs increase genic precision and are continuously being added to metazoan genomes through geologic time, miRNAs might be instrumental for canalization of development and morphological evolution. Nonetheless, an outstanding question remains: how are new miRNAs constantly evolving? To address this question, we assessed the miRNA complements of four deuterostome species, chosen because of their sequenced genomes and well‐resolved phylogeny. Our comparative analysis shows that each of these four species is characterized by a unique repertoire of miRNAs, with few instances of miRNA loss. Moreover, we find that almost half of the miRNAs identified in this study are located in intronic regions of protein coding genes, suggesting that new miRNAs might arise from intronic regions in a process we term intronic exaptation. We also show that miRNAs often occur within cotranscribed clusters, and describe the biological function of one of these conserved clusters, the miR‐1/miR‐133 cluster. Taken together, our work shows that miRNAs can easily emerge within already transcribed regions of DNA, whether it be introns or preexisting clusters of miRNAs and/or miRNAs and protein coding genes, and because of their regulatory roles, these novel players change the structure of gene regulatory networks, with potential macroevolutionary results.     

miRNA–miRNA interaction implicates for potential mutual regulatory pattern

Background

Natural or endogenous sense/antisense miRNAs, located on sense and antisense strands in the same genomic region, respectively, are detected recently. However, little is known about these miRNA pairs, especially for their distributions in different animal species. We herein present systematic analysis of them in human, mouse and rat miRNAs, and their expression patterns based on deep sequencing datasets.

Methods and results

The phenomenon of miRNA–miRNA interaction could be detected in different animal species. The common miRNAs pairs were found across species. These miRNA pairs could form miRNA:miRNA duplex with complete complementary structure, and were prone to be located on specific chromosomes. They might be homologous miRNA genes (especially in human), or clustered in a gene cluster (especially in rat), or simultaneously detected in different genomic regions due to multicopy pre-miRNAs. Remarkably, some miRNA pairs, located in different genomic regions, also showed complementarity as well as endogenous sense/antisense miRNAs. Based on published deep sequencing datasets, one member of miRNA pairs always was abundantly expressed, whereas another was quite rare. Rare common target mRNAs of these miRNA pairs were predicted.

Conclusions

Interaction between miRNAs and significant expression divergence implied complex potential mutual regulatory pattern in the miRNA world. The study would enrich miRNA regulatory network.     

Low microsatellite frequencies in neuron and brain expressed microRNAs

The locations of microsatellites in mammalian genomes are restricted by purifying selection in a number of ways. For example, with the exception of some trinucleotide repeats they are excluded from protein coding regions of genomes because of their tendency to cause frameshift mutations. Here we investigate whether purifying selection might affect the types and frequencies of microsatellites in microRNA (miRNA). We concentrate on miRNAs expressed in neurons and the brain (NB-miRNAs) as microsatellites in these genes might give rise to similar effects as disease-causing repeats in protein coding genes. We show that in human miRNAs in general AG and AT microsatellites are reduced in frequency compared to AC repeats and that NB-miRNA genes contain significantly fewer microsatellites than expected from frequencies of microsatellites in other miRNA genes. NB-miRNAs show lower levels of sequence divergence in comparisons of human-macaque orthologues and more often have detectable orthologues in non-human mammals than non-NB-miRNAs. This suggests that microsatellites in miRNAs may indeed be constrained by purifying selection and that the strength of this selection may differ between NB-miRNAs and non-NB-miRNAs. We identify a number of ways in which the potential disruption of pre-miRNA secondary structure might result in purifying selection. However other, non-selective forces could also play a role in generating the biases observed in miRNA microsatellites.     

Data mining for miRNAs and their targets in the Triticeae.

MicroRNAs (miRNAs) and the mRNA targets of miRNAs were identified by sequence complementarity within a DNA sequence database for species of the Triticeae. Data screening identified 28 miRNA precursor sequences from 15 miRNA families that contained conserved mature miRNA sequences within predicted stem-loop structures. In addition, the identification of 337 target sequences among Triticeae genes provided further evidence of the existence of 26 miRNA families in the cereals. MicroRNA targets included genes that are homologous to known targets in diverse model species as well as novel targets. MicroRNA precursors and targets were identified in 10 related species, though the great majority of them were identified in bread wheat, Triticum aestivum, and barley, Hordeum vulgare, the two species with the largest EST data sets among the Triticeae.     

Altered miRNA repertoire in the simplified chordate, Oikopleura dioica

Recent studies reveal correlation between microRNA (miRNA) innovation and increased developmental complexity. This is exemplified by dramatic expansion of the miRNA inventory in vertebrates, a lineage where genome duplication has played a significant evolutionary role. Urochordates, the closest extant group to the vertebrates, exhibit an opposite trend to genome and morphological simplification. We show that the urochordate, larvacean, Oikopleura dioica, possesses the requisite miRNA biogenic machinery. The miRNAs isolated by small RNA cloning were expressed throughout the short life cycle, a number of which were stocked as maternal determinants prior to rapid embryonic development. We identify sex-specific miRNAs that appeared as male/female gonad differentiation became apparent and were maintained throughout spermatogenesis. Whereas 80% of mammalian miRNAs are hosted in introns of protein-coding genes, the majority of O. dioica miRNA loci were located in antisense orientations to such genes. Including sister group ascidians in analysis of the urochordate miRNA repertoire, we find that 11 highly conserved bilaterian miRNA families have been lost or derived to the point they are not recognizable in urochordates and a further 4 of these families are absent in larvaceans. Subsequent to this loss/derivation, at least 29 novel miRNA families have been acquired in larvaceans. This suggests a profound reorganization of the miRNA repertoire integral to evolution in the urochordate lineage.