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The Hox cluster microRNA miR-615: a case study of intronic microRNA evolution.

Quah S, Holland PW - Evodevo (2015)

Bottom Line: The 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS UK.

ABSTRACT

Background: 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 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.

Results: Alignment 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.

Conclusions: The 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.

No MeSH data available.


Related in: MedlinePlus

Part of a Hoxc5 intronic alignment across tetrapods corresponding to the eutherian mir-615 region, extracted from an alignment of Hoxc5 loci including exons. The complete alignment is provided in Additional file 3
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Fig2: Part of a Hoxc5 intronic alignment across tetrapods corresponding to the eutherian mir-615 region, extracted from an alignment of Hoxc5 loci including exons. The complete alignment is provided in Additional file 3

Mentions: The syntenic position of mir-615 within a highly conserved Hox gene allows for direct comparisons of the corresponding region to be made between vertebrate species. In human and mouse, mir-615 is located within the intron of Hoxc5. We performed alignments of this intron and its flanking coding exons across the four main eutherian lineages (Laurasiatheria, Euarchontoglires, Afrotheria, and Xenarthra), non-eutherian mammals and other tetrapods to examine sequence conservation across the syntenic position of mir-615 (Fig. 2, Additional file 3: Supplement S3A). As no sequence data for Hoxc5 were available for Xenarthra, we sequenced the corresponding region from sloth (Choloepus didactylus) and anteater (Myrmecophaga tridactyla) using primers designed against highly conserved regions within vertebrate Hoxc5 coding regions (Additional file 1: Supplement S1). Sequence alignments reveal strong similarity to other eutherian mir-615 loci (Fig. 2). In marsupials, both the Tasmanian devil (Sarcophilus harrisii) and the tammar wallaby (Macropus eugenii) possess a sequence resembling eutherian mir-615 within Hoxc5. However, the regions corresponding to the mature miR-615 products differ slightly from the corresponding eutherian versions. We were unable to amplify the Hoxc5 gene from any monotremes with the same primers. This genomic region is also missing in the platypus (Ornithorhynchus anatinus) genome assembly.Fig. 2


The Hox cluster microRNA miR-615: a case study of intronic microRNA evolution.

Quah S, Holland PW - Evodevo (2015)

Part of a Hoxc5 intronic alignment across tetrapods corresponding to the eutherian mir-615 region, extracted from an alignment of Hoxc5 loci including exons. The complete alignment is provided in Additional file 3
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4597612&req=5

Fig2: Part of a Hoxc5 intronic alignment across tetrapods corresponding to the eutherian mir-615 region, extracted from an alignment of Hoxc5 loci including exons. The complete alignment is provided in Additional file 3
Mentions: The syntenic position of mir-615 within a highly conserved Hox gene allows for direct comparisons of the corresponding region to be made between vertebrate species. In human and mouse, mir-615 is located within the intron of Hoxc5. We performed alignments of this intron and its flanking coding exons across the four main eutherian lineages (Laurasiatheria, Euarchontoglires, Afrotheria, and Xenarthra), non-eutherian mammals and other tetrapods to examine sequence conservation across the syntenic position of mir-615 (Fig. 2, Additional file 3: Supplement S3A). As no sequence data for Hoxc5 were available for Xenarthra, we sequenced the corresponding region from sloth (Choloepus didactylus) and anteater (Myrmecophaga tridactyla) using primers designed against highly conserved regions within vertebrate Hoxc5 coding regions (Additional file 1: Supplement S1). Sequence alignments reveal strong similarity to other eutherian mir-615 loci (Fig. 2). In marsupials, both the Tasmanian devil (Sarcophilus harrisii) and the tammar wallaby (Macropus eugenii) possess a sequence resembling eutherian mir-615 within Hoxc5. However, the regions corresponding to the mature miR-615 products differ slightly from the corresponding eutherian versions. We were unable to amplify the Hoxc5 gene from any monotremes with the same primers. This genomic region is also missing in the platypus (Ornithorhynchus anatinus) genome assembly.Fig. 2

Bottom Line: The 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS UK.

ABSTRACT

Background: 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 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.

Results: Alignment 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.

Conclusions: The 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.

No MeSH data available.


Related in: MedlinePlus