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

Abstract

BackgroundMilk 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.ResultsWe 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 < 10-8 for 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.ConclusionThe 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).

Identification and evolution of the orphan genes in the domestic silkworm,Bombyx mori

“…The theoretical pI (isoelectric point) of a protein is important for solubility, subcellular localization and interaction [32,33]. Thus, the shift of the value is always considered as the changes of the protein functions [34]. We found that silkworm orphan proteins have significantly higher average pI value (9.18 ± 2.41) than nonorphan proteins (7.62 ± 2.09) (Mann-Whitney U test, P < 0.001) ( Fig.…”

Lama glama αS1-casein: Identification of new polymorphisms in the CSN1S1 gene

“…The first amino acid change has no effect on the polarity of the mature protein, whereas the second slightly shifts the predicted isoelectric point (pI) from 4.78 to 4.85 as consequence of the different chemical properties of the involved amino acid, from neutral (tyrosine) to basic (histidine). As pI and charge of milk proteins are important for their interactions and properties (Khaldi and Shield, 2011), protein variants were submitted to the NetSurfP ver. 1.1 software (http://www.cbs.dtu.dk/ services/NetSurfP/) to predict the secondary structure and detect potential modifications of the surface accessibility for the investigated amino acid.…”

Association of rs1042522 Polymorphism with Increased Risk of Prostate Adenocarcinoma in the Pakistani Population and its HuGE Review

“…The biochemical differences, nature and location of amino acid substitution can affect the protein in various ways and is therefore important to determine whether it can alter the protein function. Isoelectric focusing point (pI) and charge is important for the solubility and interaction of a protein (Nandi et al, 2005;Khaldi and Shields, 2011). It is clear from the research that, pI of a protein can vary due to insertions, deletions, substitutions and the ecology of the organism (Kiraga et al, 2007).…”

“…Isoelectric focusing point (pI) and charge is important for the solubility and interaction of a protein (Nandi et al, 2005;Khaldi and Shields, 2011). Theoretical pI of the p53 proteins were predicted by using Bioinformatics tools and were observed 6.34 and 6.47 for the native and polymorphic respectively.…”