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.

1. Distribution of events of positive selection and
population differentiation in a metabolic pathway: the
case of asparagine N-glycosylation

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. 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. 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 protein's stability and is
frequently used as a signal

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. 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. 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. 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. Downstream part of
Glycosylation is involved in
immunity
Protein A Protein A
Surface of host's cell Surface of pathogen

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. Results
 Signatures of high
FST are more
frequent in the
downstream part
of the pathway
 iHS signals are
more or less
equally
distributed

12. My group!
Protein A
● Jaume Bertranpetit (PI)
● Hafid Laayouni (my
supervisor)
● Ludovica Montanucci
● Pierre Luisi
● Brandon Invergo
● Marc Pybus
● Ferran Casals
● Martino Colombo