Loughran, NB, O'Connor, B, Ó'Fágáin, C et al. (1 more author) (2008) The phylogeny of the mammalian heme peroxidases and the evolution of their diverse functions. BMC Evolutionary Biology, 8 (1). 101. ISSN 1471-2148
Abstract
Background
The mammalian heme peroxidases (MHPs) are a medically important group of enzymes. Included in this group are myeloperoxidase, eosinophil peroxidase, lactoperoxidase, and thyroid peroxidase. These enzymes are associated with such diverse diseases as asthma, Alzheimer's disease and inflammatory vascular disease. Despite much effort to elucidate a clearer understanding of the function of the 4 major groups of this multigene family, we still do not have a clear understanding of their relationships to each other.
Results
Sufficient signal exists for the resolution of the evolutionary relationships of this family of enzymes. We demonstrate, using a root mean squared deviation statistic, how the removal of the fastest evolving sites aids in the minimisation of the effect of long branch attraction and the generation of a highly supported phylogeny. Based on this phylogeny we have pinpointed the amino acid positions that have most likely contributed to the diverse functions of these enzymes. Many of these residues are in close proximity to sites implicated in protein misfolding, loss of function or disease.
Conclusion
Our analysis of all available genomic sequence data for the MHPs from all available completed mammalian genomes, involved sophisticated methods of phylogeny reconstruction and data treatment. Our study has (i) fully resolved the phylogeny of the MHPs and the subsequent pattern of gene duplication, and (ii), we have detected amino acids under positive selection that have most likely contributed to the observed functional shifts in each type of MHP.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2008 Loughran et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Root Means Square Deviation; Gene Duplication Event; Much Recent Common Ancestor; Long Branch Attraction; Functional Shift |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 09 Sep 2019 10:23 |
Last Modified: | 23 Jun 2023 22:11 |
Status: | Published |
Publisher: | BMC |
Identification Number: | 10.1186/1471-2148-8-101 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:103530 |