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Identification of Distant Agouti-Like Sequences and Re-Evaluation of the Evolutionary History of the Agouti-Related Peptide (AgRP)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 7, e40982- p.Article in journal (Refereed) Published
Abstract [en]

The Agouti-like peptides including AgRP, ASIP and the teleost-specific A2 (ASIP2 and AgRP2) peptides have potent and diverse functional roles in feeding, pigmentation and background adaptation mechanisms. There are contradictory theories about the evolution of the Agouti-like peptide family as well the nomenclature. Here we performed comprehensive mining and annotation of vertebrate Agouti-like sequences. We identified A2 sequences from salmon, trout, seabass, cod, cichlid, tilapia, gilt-headed sea bream, Antarctic toothfish, rainbow smelt, common carp, channel catfish and interestingly also in lobe-finned fish. Moreover, we surprisingly found eight novel homologues from the kingdom of arthropods and three from fungi, some sharing the characteristic C-x(6)-C-C motif which are present in the Agouti-like sequences, as well as approximate sequence length (130 amino acids), positioning of the motif sequence and sharing of exon-intron structures that are similar to the other Agouti-like peptides providing further support for the common origin of these sequences. Phylogenetic analysis shows that the AgRP sequences cluster basally in the tree, suggesting that these sequences split from a cluster containing both the ASIP and the A2 sequences. We also used a novel approach to determine the statistical evidence for synteny, a sinusoidal Hough transform pattern recognition technique. Our analysis shows that the teleost AgRP2 resides in a chromosomal region that has synteny with Hsa 8, but we found no convincing synteny between the regions that A2, AgRP and ASIP reside in, which would support that the Agouti-like peptides were formed by whole genome tetraplodization events. Here we suggest that the Agouti-like peptide genes were formed through classical subsequent gene duplications where the AgRP is the most distantly related to the three other members of that group, first splitting from a common ancestor to ASIP and A2, and then later the A2 split from ASIP followed by a split resulting in ASIP2 and AgRP2.

Place, publisher, year, edition, pages
2012. Vol. 7, no 7, e40982- p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-179576DOI: 10.1371/journal.pone.0040982ISI: 000306466100103OAI: oai:DiVA.org:uu-179576DiVA: diva2:545396
Available from: 2012-08-20 Created: 2012-08-20 Last updated: 2017-12-07Bibliographically approved

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Västermark, ÅkeKrishnan, ArunkumarFredriksson, RobertSchiöth, Helgi B.
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