Shift in the isoelectric-point of milk proteins as a consequence of adaptive divergence between the milks of mammalian species

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Background: Milk proteins are required to proceed through a variety of conditions of radically varying pH, which are not identical across mammalian digestive systems. We wished to investigate if the shifts in these requirements have resulted in marked changes in the isoelectric point and charge of milk proteins during evolution.Results: We investigated nine major milk proteins in 13 mammals. In comparison with a group of orthologous non-milk proteins, we found that 3 proteins κ-casein, lactadherin, and muc1 have undergone the highest change in isoelectric point during evolution. The pattern of non-synonymous substitutions indicate that selection has played a role in the isoelectric point shift, since residues that show significant evidence of positive selection are much more likely to be charged (p = 0.03 for κ-casein; p < 10-8for muc1). However, this selection does not appear to be solely due to adaptation to the diversity of mammalian digestive systems, since striking changes are seen among species that resemble each other in terms of their digestion.Conclusion: The changes in charge are most likely due to changes of other protein functions, rather than an adaptation to the different mammalian digestive systems. These functions may include differences in bioactive peptide releases in the gut between different mammals, which are known to be a major contributing factor in the functional and nutritional value of mammalian milk. This raises the question of whether bovine milk is optimal in terms of particular protein functions, for human nutrition and possibly disease resistance.This article was reviewed by Fyodor Kondrashov, David Liberles (nominated by David Ardell), and Christophe Lefevre (nominated by Mark Ragan). © 2011 Khaldi and Shields; licensee BioMed Central Ltd.




Khaldi, N., & Shields, D. C. (2011). Shift in the isoelectric-point of milk proteins as a consequence of adaptive divergence between the milks of mammalian species. Biology Direct, 6.

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