Seleção darwiniana para sítios de glicosilação Asn associada em eucariotos e vírus filogeneticamente discrepantes

Darwinian selection for sites of Asn-linked glycosylation in phylogenetically disparate eukaryotes and viruses

Jike Cuia, Temple Smithb,c, Phillips W. Robbinsa,1 and John Samuelsona

+Author Affiliations

aDepartment of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, MA 02118; and

bGraduate Program in Bioinformatics, and

cDepartment of Biomedical Engineering, Boston University, Boston, MA 02215

Contributed by Phillips W. Robbins, May 28, 2009 (received for review February 20, 2009)

Abstract

Numerous protists and rare fungi have truncated Asn-linked glycan precursors and lack N-glycan-dependent quality control (QC) systems for glycoprotein folding in the endoplasmic reticulum. Here, we show that the abundance of sequons (NXT or NXS), which are sites for N-glycosylation of secreted and membrane proteins, varies by more than a factor of 4 among phylogenetically diverse eukaryotes, based on a few variables. There is positive correlation between the density of sequons and the AT content of coding regions, although no causality can be inferred. In contrast, there appears to be Darwinian selection for sequons containing Thr, but not Ser, in eukaryotes that have N-glycan-dependent QC systems. Selection for sequons with Thr, which nearly doubles the sequon density in human secreted and membrane proteins, occurs by an increased conditional probability that Asn and Thr are present in sequons rather than elsewhere. Increasing sequon densities of the hemagglutinin (HA) of influenza viruses A/H3N2 and A/H1N1 during the past few decades of human infection also result from an increased conditional probability that Asn, Thr, and Ser are present in sequons rather than elsewhere. In contrast, there is no selection on sequons by this mechanism in HA of A/H5N1 or 2009 A/H1N1 (Swine flu). Very strong selection for sequons with both Thr and Ser in glycoprotein of Mr 120,000 (gp120) of HIV and related retroviruses results from this same mechanism, as well as amino acid composition bias and increases in AT content. We conclude that there is Darwinian selection for sequons in phylogenetically disparate eukaryotes and viruses.

Asn-linked glycan evolution influenza sequon N-glycan-dependent quality control

Footnotes

1To whom correspondence should be addressed. E-mail: robbinsp@bu.edu

Author contributions: J.C., T.S., P.W.R., and J.S. designed research; J.C. performed research; T.S. contributed new reagents/analytic tools; J.C., T.S., P.W.R., and J.S. analyzed data; and P.W.R. and J.S. wrote the paper.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0905818106/DCSupplemental.

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