Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylationReport as inadecuate




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BMC Evolutionary Biology

, 12:98

First Online: 25 June 2012Received: 31 December 2011Accepted: 25 June 2012DOI: 10.1186-1471-2148-12-98

Cite this article as: Dall’Olio, G.M., Laayouni, H., Luisi, P.
et al.
BMC Evol Biol 2012 12: 98.
doi:10.1186-1471-2148-12-98

Abstract

BackgroundAsparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes.
This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment and innate immunity.
Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection.
We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints.

ResultsOur results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway.
Moreover, events of positive selection are frequent on genes that are known to be at bifurcation points, and that are identified as being in key position by a network-level analysis such as MGAT3 and GCS1.

ConclusionsThese findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations.
Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints.
Our results support the hypothesis that genes involved in constitutive processes can be expected to show lower population differentiation, while genes involved in traits related to the environment should show higher variability.
Taken together, this work broadens our knowledge on how events of population differentiation and of positive selection are distributed among different parts of a metabolic pathway.

KeywordsHomo sapiens Positive selection Population differentiation Asparagine N-Glycosylation Glycosylation Pathway analysis Calnexin-calreticulin cycle Adaptation to environment Electronic supplementary materialThe online version of this article doi:10.1186-1471-2148-12-98 contains supplementary material, which is available to authorized users.

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Author: Giovanni Marco Dall’Olio - Hafid Laayouni - Pierre Luisi - Martin Sikora - Ludovica Montanucci - Jaume Bertranpetit

Source: https://link.springer.com/



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