Abstract

Eukaryotic genomes are pervasively transcribed. A large fraction of the transcriptional output consists of long, mRNA-like, non-protein-coding transcripts (mlncRNAs). The evolutionary history of mlncRNAs is still largely uncharted territory. In this contribution, we explore in detail the evolutionary traces of the eosinophil granule ontogeny transcript (EGOT), an experimentally confirmed representative of an abundant class of totally intronic non-coding transcripts (TINs). EGOT is located antisense to an intron of the ITPR1 gene. We computationally identify putative EGOT orthologs in the genomes of 32 different amniotes, including orthologs from primates, rodents, ungulates, carnivores, afrotherians, and xenarthrans, as well as putative candidates from basal amniotes, such as opossum or platypus. We investigate the EGOT gene phylogeny, analyze patterns of sequence conservation, and the evolutionary conservation of the EGOT gene structure. We show that EGO-B, the spliced isoform, may be present throughout the placental mammals, but most likely dates back even further. We demonstrate here for the first time that the whole EGOT locus is highly structured, containing several evolutionary conserved, and thermodynamic stable secondary structures. Our analyses allow us to postulate novel functional roles of a hitherto poorly understood region at the intron of EGO-B which is highly conserved at the sequence level. The region contains a novel ITPR1 exon and also conserved RNA secondary structures together with a conserved TATA-like element, which putatively acts as a promoter of an independent regulatory element.

Highlights

  • Large surveys of transcriptomes, such as ENCODE (ENCODE Project Consortium et al, 2007) and FANTOM (Maeda et al, 2006), demonstrated that eukaryotic genomes are pervasively transcribed (Jacquier, 2009)

  • We explore in detail the evolution of one particular example of the latter class, the eosinophil granule ontogeny transcript (EGOT)

  • We have traced here the evolutionary history of EGOT, one of the first totally intronic long ncRNA that has been studied in detail

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Summary

Introduction

Large surveys of transcriptomes, such as ENCODE (ENCODE Project Consortium et al, 2007) and FANTOM (Maeda et al, 2006), demonstrated that eukaryotic genomes are pervasively transcribed (Jacquier, 2009). MRNA-like, non-proteincoding transcripts (mlncRNAs) are an important component of this transcriptional output, often arising from regions unlinked to annotated protein-coding genes (Khalil et al, 2009). The evidence for wide-spread evolutionary constraints on the sequence evolution of ncRNAs is the most direct evidence that at least a large fraction of them is functional, we know very little about the evolutionary history of individual transcripts. In contrast to protein-coding genes or short structured ncRNAs, for which comprehensive evolutionary information is available in databases like Pfam (Finn et al, 2010) or Rfam (Gardner et al, 2011), there is no comparable resource for long ncRNAs. The lncRNA database (Amaral et al, 2011) is a first pioneering step in this direction, predominately compiling non-coding transcripts from the model organisms human and mouse

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