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Open Access Highly Accessed Research article

The phylogeny of the mammalian heme peroxidases and the evolution of their diverse functions

Noeleen B Loughran1, Brendan O'Connor2, Ciarán Ó'Fágáin2 and Mary J O'Connell12*

Author affiliations

1 Bioinformatics and Molecular Evolution Group, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland

2 School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland

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Citation and License

BMC Evolutionary Biology 2008, 8:101  doi:10.1186/1471-2148-8-101

Published: 27 March 2008

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.