The University of Southampton
University of Southampton Institutional Repository

Phocid seal leptin: tertiary structure and hydrophobic receptor binding site preservation during distinct leptin gene evolution

Hammond, John A., Hauton, Chris, Bennett, Kimberley A. and Hall, Ailsa J. (2012) Phocid seal leptin: tertiary structure and hydrophobic receptor binding site preservation during distinct leptin gene evolution PLoS ONE, 7, (4), e35395. (doi:10.1371/journal.pone.0035395).

Record type: Article


The cytokine hormone leptin is a key signalling molecule in many pathways that control physiological functions. Although leptin demonstrates structural conservation in mammals, there is evidence of positive selection in primates, lagomorphs and chiropterans. We previously reported that the leptin genes of the grey and harbour seals (phocids) have significantly diverged from other mammals. Therefore we further investigated the diversification of leptin in phocids, other marine mammals and terrestrial taxa by sequencing the leptin genes of representative species. Phylogenetic reconstruction revealed that leptin diversification was pronounced within the phocid seals with a high dN/dS ratio of 2.8, indicating positive selection. We found significant evidence of positive selection along the branch leading to the phocids, within the phocid clade, but not over the dataset as a whole. Structural predictions indicate that the individual residues under selection are away from the leptin receptor (LEPR) binding site. Predictions of the surface electrostatic potential indicate that phocid seal leptin is notably different to other mammalian leptins, including the otariids. Cloning the grey seal leptin binding domain of LEPR confirmed that this was structurally conserved. These data, viewed in toto, support a hypothesis that phocid leptin divergence is unlikely to have arisen by random mutation. Based upon these phylogenetic and structural assessments, and considering the comparative physiology and varying life histories among species, we postulate that the unique phocid diving behaviour has produced this selection pressure. The Phocidae includes some of the deepest diving species, yet have the least modified lung structure to cope with pressure and volume changes experienced at depth. Therefore, greater surfactant production is required to facilitate rapid lung re-inflation upon surfacing, while maintaining patent airways. We suggest that this additional surfactant requirement is met by the leptin pulmonary surfactant production pathway which normally appears only to function in the mammalian foetus.

Other fetchObject.action_uri=info_doi%2F10.1371%2Fjournal.pone.0035395&representation=PDF - Version of Record
Available under License Other.
Download (763kB)

More information

Published date: 2012
Organisations: Ocean Biochemistry & Ecosystems


Local EPrints ID: 337592
ISSN: 1932-6203
PURE UUID: 29609e92-d77d-4bb4-8be6-7b143fd5026e
ORCID for Chris Hauton: ORCID iD

Catalogue record

Date deposited: 30 Apr 2012 09:00
Last modified: 18 Jul 2017 06:02

Export record



Author: John A. Hammond
Author: Chris Hauton ORCID iD
Author: Kimberley A. Bennett
Author: Ailsa J. Hall

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.