Abstract
BackgroundIntrons represent a potentially rich source of existing transcription for the evolution of novel microRNAs (miRNAs). Within the Hox gene clusters, a miRNA gene, miR-615, is located within the intron of the Hoxc5 gene. This miRNA has a restricted phylogenetic distribution, providing an opportunity to examine the origin and evolution of a new miRNA within the intron of a developmentally-important homeobox gene.ResultsAlignment and structural analyses show that the sequence is highly conserved across eutherian mammals and absent in non-mammalian tetrapods. Marsupials possess a similar sequence which we predict will not be efficiently processed as a miRNA. Our analyses suggest that transcription of HOXC5 in humans is accompanied by expression of miR-615 in all cases, but that the miRNA can also be transcribed independently of its host gene through the use of an intragenic promoter. We present scenarios for the evolution of miR-615 through intronic exaptation, and speculate on the acquisition of independent transcriptional regulation. Target prediction and transcriptomic analyses suggest that the dominant product of miR-615 is involved in the regulation of growth and a range of developmental processes.ConclusionsThe miR-615 gene evolved within the intron of Hoxc5 in the ancestor of placental mammals. Using miR-615 as a case study, we propose a model by which a functional miRNA can emerge within an intron gradually, by selection on secondary structure followed by evolution of an independent miRNA promoter. The location within a Hox gene intron is of particular interest as the miRNA is specific to placental mammals, is co-expressed with its host gene and may share complementary functions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13227-015-0027-1) contains supplementary material, which is available to authorized users.
Highlights
Introns represent a potentially rich source of existing transcription for the evolution of novel microRNAs
To determine whether miR-615 is present in other amniotes, we searched for its precursor gene sequence in the genomes of other eutherians, plus a marsupial (Monodelphis domestica), a monotreme (Ornithorhynchus anatinus) and three non-mammalian vertebrates
The Hox cluster miRNA mir-615 represents an interesting case of acquisition of a novel miRNA by intronic exaptation and an unusual example of a new functional gene arising within a conserved Hox gene cluster
Summary
Introns represent a potentially rich source of existing transcription for the evolution of novel microRNAs (miRNAs). Within the Hox gene clusters, a miRNA gene, miR-615, is located within the intron of the Hoxc gene. This miRNA has a restricted phylogenetic distribution, providing an opportunity to examine the origin and evolution of a new miRNA within the intron of a developmentally-important homeobox gene. We analyse the origin and evolution of miR615, a mammalian intronic miRNA located within a Hox cluster. Analyse and integrate data on the regulation, expression pattern and likely biological roles of miR-615, in concert with comparative analysis, and propose how the origin of this miRNA contributed to eutherian evolution and development. Homeobox genes form a large, diverse superclass with a wide range of roles in metazoan developmental biology.
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