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Genome-wide comparative analysis of microRNAs in three non-human primates.

ABSTRACT: BACKGROUND: MicroRNAs (miRNAs) are negative regulators of gene expression in multicellular eukaryotes. With the recently completed sequencing of three primate genomes, the study of miRNA evolution within the primate lineage has only begun and may be expected to provide the genetic and molecular explanations for many phenotypic differences between human and non-human primates. FINDINGS: We scanned all three genomes of non-human primates, including chimpanzee (Pan troglodytes), orangutan (Pongo pygmaeus), and rhesus monkey (Macaca mulatta), for homologs of human miRNA genes. Besides sequence homology analysis, our comparative method relies on various postprocessing filters to verify other features of miRNAs, including, in particular, their precursor structure or their occurrence (prediction) in other primate genomes. Our study allows direct comparisons between the different species in terms of their miRNA repertoire, their evolutionary distance to human, the effects of filters, as well as the identification of common and species-specific miRNAs in the primate lineage. More than 500 novel putative miRNA genes have been discovered in orangutan that show at least 85 percent identity in precursor sequence. Only about 40 percent are found to be 100 percent identical with their human ortholog. CONCLUSION: Homologs of human precursor miRNAs with perfect or near-perfect sequence identity may be considered to be likely functional in other primates. The computational identification of homologs with less similar sequence, instead, requires further evidence to be provided.

SUBMITTER: Brameier M

PROVIDER: S-EPMC2850348 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Genome-wide comparative analysis of microRNAs in three non-human primates.

Brameier Markus M

BMC research notes 20100309

<h4>Background</h4>MicroRNAs (miRNAs) are negative regulators of gene expression in multicellular eukaryotes. With the recently completed sequencing of three primate genomes, the study of miRNA evolution within the primate lineage has only begun and may be expected to provide the genetic and molecular explanations for many phenotypic differences between human and non-human primates.<h4>Findings</h4>We scanned all three genomes of non-human primates, including chimpanzee (Pan troglodytes), orangu ...[more]

PMID: 20214803

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Project description:BackgroundBecause species-specific gene expression is driven by species-specific regulation, understanding the relationship between sequence and function of the regulatory regions in different species will help elucidate how differences among species arise. Despite active experimental and computational research, relationships among sequence, conservation, and function are still poorly understood.ResultsWe compared transcription factor occupied segments (TFos) for 116 human and 35 mouse TFs in 546 human and 125 mouse cell types and tissues from the Human and the Mouse ENCODE projects. We based the map between human and mouse TFos on a one-to-one nucleotide cross-species mapper, bnMapper, that utilizes whole genome alignments (WGA). Our analysis shows that TFos are under evolutionary constraint, but a substantial portion (25.1% of mouse and 25.85% of human on average) of the TFos does not have a homologous sequence on the other species; this portion varies among cell types and TFs. Furthermore, 47.67% and 57.01% of the homologous TFos sequence shows binding activity on the other species for human and mouse respectively. However, 79.87% and 69.22% is repurposed such that it binds the same TF in different cells or different TFs in the same cells. Remarkably, within the set of repurposed TFos, the corresponding genome regions in the other species are preferred locations of novel TFos. These events suggest exaptation of some functional regulatory sequences into new function. Despite TFos repurposing, we did not find substantial changes in their predicted target genes, suggesting that CRMs buffer evolutionary events allowing little or no change in the TFos - target gene associations. Thus, the small portion of TFos with strictly conserved occupancy underestimates the degree of conservation of regulatory interactions.ConclusionWe mapped regulatory sequences from an extensive number of TFs and cell types between human and mouse using WGA. A comparative analysis of this correspondence unveiled the extent of the shared regulatory sequence across TFs and cell types under study. Importantly, a large part of the shared regulatory sequence is repurposed on the other species. This sequence, fueled by turnover events, provides a strong case for exaptation in regulatory elements.

Dataset Information

Genome-wide comparative analysis of microRNAs in three non-human primates.

Publications

Genome-wide comparative analysis of microRNAs in three non-human primates.

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