N-glycosylation: one pathway, two selective constraints

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This is a slideshow I prepared for presenting our paper published in BMC Evolutionary Biology http://www.biomedcentral.com/1471-2148/12/98/abstract

Apologies if the slides are not very clear, but I prepared it quickly and just for putting them in my blog.

See http://bioinfoblog.it/?p=1065 for the blog post.

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N-glycosylation: one pathway, two selective constraints

  1. 1. Distribution of events of positive selection andpopulation differentiation in a metabolic pathway: the case of asparagine N-glycosylation
  2. 2. Our hypothesis Selective constraints are  not uniform among  positions of a pathway Genes in upstream  positions, or with an  higher number of  interactions, should be  more selectively  constrained than  others
  3. 3. Pathway-level analysis Pathway databases are not yet ready for large scale  analysis  Too many false positives in the annotations  The same annotation can have multiple  interpretations So, the best approach is to focus on single  pathways, one at a time The pathway of N­Glycosylation is a good start for  studying how selective constraints are related to  pathway position and degree
  4. 4. What is Glycosylation? Glycosylation is a common form of post­ translational protein modification Almost 50% of the proteins in SwissProt are  glycosylated   (mostly membrane, secreted, signal proteins) Glycosylation increases the proteins stability and is  frequently used as a signal
  5. 5. N-glycosylation (upstream part)  Linear pathway  Produces a single sugar  called “N­Glycan  precursor”  This sugar is required  for the proper folding Adapted from Stanley, P., Schachter, H., & Taniguchi, N. (2009).N-Glycans. Essentials of Glycobiology. of most membrane  proteins
  6. 6. N-Glycosylation (upstream part) The product of the upstream part of the N­ Glycosylation pathway is used as a “label”  for the folding status of proteins. Folded proteins are marked with Unfolded proteins are marked with              or
  7. 7. N-Glycosylation (downstream part) Complex pathway  composed by  thousands of  reactions Produces multiple  sugars, important for  cell­to­cell  interactions Hossler, P., Mulukutla, B. C., & Hu, W.-S. (2007). Systems analysis of N-glycan processing in mammalian cells. PloS one, 2(1), e713. doi:10.1371/journal.pone.0000713
  8. 8. N-Glycosylation (downstream part) The products of the downstream part of the N­ Glycosylation pathway are used to “decorate”  proteins on the membrane Protein A Protein A Surface of linfocite Surface of erithrocite
  9. 9. Downstream part ofGlycosylation is involved in immunity Protein A Protein A Surface of hosts cell Surface of pathogen
  10. 10. Resume: structure of N- glycosylation pathway Upstream: linear and conserved among species Downstream: complex and related to immunity Hypothesis: genetic diversity should be higher in  the downstream part.
  11. 11. Results Signatures of high  FST are more  frequent in the  downstream part  of the pathway iHS signals are  more or less  equally  distributed
  12. 12. My group! Protein A ● Jaume Bertranpetit (PI) ● Hafid Laayouni (my  supervisor) ● Ludovica Montanucci ● Pierre Luisi ● Brandon Invergo ● Marc Pybus ● Ferran Casals ● Martino Colombo

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