Dataset Information

ANRIL/CDKN2B-AS shows two-stage clade-specific evolution and becomes conserved after transposon insertions in simians.

ABSTRACT:

Background

Many long non-coding RNA (lncRNA) genes identified in mammals have multiple exons and functional domains, allowing them to bind to polycomb proteins, DNA methyltransferases, and specific DNA sequences to regulate genome methylation. Little is known about the origin and evolution of lncRNAs. ANRIL/CDKN2B-AS consists of 19 exons on human chromosome 9p21 and regulates the expression of three cyclin-dependent kinase inhibitors (CDKN2A/ARF/CDKN2B).

Results

ANRIL/CDKN2B-AS originated in placental mammals, obtained additional exons during mammalian evolution but gradually lost them during rodent evolution, and reached 19 exons only in simians. ANRIL lacks splicing signals in mammals. In simians, multiple transposons were inserted and transformed into exons of the ANRIL gene, after which ANRIL became highly conserved. A further survey reveals that multiple transposons exist in many lncRNAs.

Conclusions

ANRIL shows a two-stage, clade-specific evolutionary process and is fully developed only in simians. The domestication of multiple transposons indicates an impressive pattern of "evolutionary tinkering" and is likely to be important for ANRIL's structure and function. The evolution of lncRNAs and that of transposons may be highly co-opted in primates. Many lncRNAs may be functional only in simians.

SUBMITTER: He S

PROVIDER: S-EPMC3831594 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

ANRIL/CDKN2B-AS shows two-stage clade-specific evolution and becomes conserved after transposon insertions in simians.

He Sha S Gu Weiling W Li Yize Y Zhu Hao H

BMC evolutionary biology 20131113

<h4>Background</h4>Many long non-coding RNA (lncRNA) genes identified in mammals have multiple exons and functional domains, allowing them to bind to polycomb proteins, DNA methyltransferases, and specific DNA sequences to regulate genome methylation. Little is known about the origin and evolution of lncRNAs. ANRIL/CDKN2B-AS consists of 19 exons on human chromosome 9p21 and regulates the expression of three cyclin-dependent kinase inhibitors (CDKN2A/ARF/CDKN2B).<h4>Results</h4>ANRIL/CDKN2B-AS or ...[more]

PMID: 24225082

Similar Datasets

Project description:The methyl-CpG Binding Protein two gene (MECP2) encodes a multifunctional protein comprising two isoforms involved in nuclear organization and regulation of splicing and mRNA template activity. This gene is normally expressed in all tissues, with a higher expression level in the brain during neuronal maturation. Loss of MECP2 function is the primary cause of Rett syndrome (RTT) in humans, a dominant, X-linked disorder dramatically affecting neural and motor development.We investigated the molecular evolution of MECP2 in several primate taxa including 36 species in 16 genera of neotropical (platyrrhine) primates. The coding region of the MECP2_e2 isoform showed a high level of evolutionary conservation among humans and other primates, with amino acid substitutions in 14 codons and one in-frame insertion of a single serine codon, between codons 357 and 358, in Ateles paniscus. Most substitutions occurred in noncritical regions of MECP2 and the majority of the algorithms used for analyzing selection did not provide evidence of positive selection. Conversely, we found 48 sites under negative selection in different regions, 23 of which were consistently found by three different algorithms. Similar to an inverted Alu insert found previously in a lesser ape at a parallel location, one Alu insertion of approximately 300 bp in Cebus and Sapajus was found in intron 3. Phylogenetic reconstruction of the intron 3 data provided a topology that was coincident with the consensus arrangement of the primate taxa. RNAseq data in the neotropical primate Callimico goeldii revealed a novel transcript consisting of a noncontinuous region of the human-homologous intron 2 in this species; this transcript accounted for two putative polypeptides.Despite the remarkable evolutionary conservation of MECP2, one in-frame codon insertion was observed in A. paniscus, and one region of intron 3 was affected by a trans-specific Alu retrotransposition in two neotropical primate genera. Moreover, identification of novel MECP2 transcripts in Callimico suggests that part of a homologous human intronic region might be expressed, and that the potential open reading frame in this region might be a subject of interest in RTT patients who carry an apparently normal MECP2 sequence.

Project description:BACKGROUND:A critical topic of insertional mutagenesis experiments performed on model organisms is mapping the hits of artificial transposons (ATs) at nucleotide level accuracy. Mapping errors may occur when sequencing artifacts or mutations as single nucleotide polymorphisms (SNPs) and small indels are present very close to the junction between a genomic sequence and a transposon inverted repeat (TIR). Another particular item of insertional mutagenesis is mapping of the transposon self-insertions and, to our best knowledge, there is no publicly available mapping tool designed to analyze such molecular events. RESULTS:We developed Genome ARTIST, a pairwise gapped aligner tool which works out both issues by means of an original, robust mapping strategy. Genome ARTIST is not designed to use next-generation sequencing (NGS) data but to analyze ATs insertions obtained in small to medium-scale mutagenesis experiments. Genome ARTIST employs a heuristic approach to find DNA sequence similarities and harnesses a multi-step implementation of a Smith-Waterman adapted algorithm to compute the mapping alignments. The experience is enhanced by easily customizable parameters and a user-friendly interface that describes the genomic landscape surrounding the insertion. Genome ARTIST is functional with many genomes of bacteria and eukaryotes available in Ensembl and GenBank repositories. Our tool specifically harnesses the sequence annotation data provided by FlyBase for Drosophila melanogaster (the fruit fly), which enables mapping of insertions relative to various genomic features such as natural transposons. Genome ARTIST was tested against other alignment tools using relevant query sequences derived from the D. melanogaster and Mus musculus (mouse) genomes. Real and simulated query sequences were also comparatively inquired, revealing that Genome ARTIST is a very robust solution for mapping transposon insertions. CONCLUSIONS:Genome ARTIST is a stand-alone user-friendly application, designed for high-accuracy mapping of transposon insertions and self-insertions. The tool is also useful for routine aligning assessments like detection of SNPs or checking the specificity of primers and probes. Genome ARTIST is an open source software and is available for download at www.genomeartist.ro and at GitHub (https://github.com/genomeartist/genomeartist ).

Dataset Information

ANRIL/CDKN2B-AS shows two-stage clade-specific evolution and becomes conserved after transposon insertions in simians.

Background

Results

Conclusions

Publications

ANRIL/CDKN2B-AS shows two-stage clade-specific evolution and becomes conserved after transposon insertions in simians.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets