How to detect natural selection Using online tools

1. Detecting natural
Selection using
B I O 5 3 4
Tu t o r i a l B y F a b r i c e K e n t a t c h i m e

2. Background on
natural selection
What is natural
selection?
Types of selections
Some statistical
methods to detect
selection
Detecting
selection in HLA-C
gene in some
mammal species
What is Data
monkey tool
HLA-C gene and its
importance
Purifying, neutral
and diversifying
selection of HLA-C
gene in some
mammal species
Tutorial’s outline

3. What is natural selection?

4. How does
selection work?
• Differential reproduction is caused by differences
among individuals in such traits as:
• mortality
• fertility (offspring)
• fecundity (gametes)
• mating success
• viability of offspring
• All these factors
together influence an individual’s
• fitness: a measure of an individual’s ability to
survive and reproduce relative to the rest of
the population

5. Types of
selections
• Stabilizing,
• directional
• diversifying selection
Most protein coding genes evolve under purifying selection of widely varying strength, to preserve
protein function, and a few evolve under positive selection

6. Purifying Selection
• Negative Selection
• Acts to select out deleterious mutations in coding or regulatory sequences
• Tends to maintain constancy of DNA sequences... More constant than would be expected with new
mutations and if genetic drift were acting alone (dN/dS < 1)

7. Diversifying
selection
• Diversifying selection: Natural
selection simultaneously favors
phenotypes at both extremes of the
distribution.
• Individuals at the extremes contribute
more offspring than those in the center,
producing two peaks in the distribution
of a particular trait

8. Some statistical methods to detect
selection
Natural
selection
Fixed
Effects
Likelihood
(FEL)
BUSTED
MEME
Uses a maximum-likelihood approach to infer
nonsynonymous (dN)and synonymous (dS)
substitution rate on a pair site basis for a given coding
alignment and corresponding phylogeny. The
assumption is that the selection pressure for each site
is constant along the entire phylogeny.
Mixed Effects Model of Evolution
employs a mixed-effects maximum
likelihood approach to test the hypothesis
that individual sites have been subject to
episodic positive or diversifying selection.
In other words, MEME aims to detect
sites evolving under positive selection
under a proportion of branches.
Branch-site Unrestricted Statistical Test
for Episodic Diversification) provides a gene-
wide (not site-specific) test for positive
selection by asking whether a gene has
experienced positive selection at at least one
site on at least one branch.

9. FEL The rate matrix for the
model used in the FEL
method is
Sergei L. Kosakovsky Pond and Simon D. W. Frost
(2005)

10. ?

11. What is data monkey?
Detects natural selection
MEME
FEL
BUSTED
Aligned sequences

12. HLA-C gene
and its
importance
• MHC is important in immune response
• VERY diverse in humans (i.e., many
alleles)
• Chimpanzees have experienced a
selective sweep at MHC (i.e., few
alleles)
• May be subject to frequency dependent
selection if pathogens have evolved to
evade immune detection in individuals
carrying the higher frequency alleles

13. Alpha/beta site-
level estimate
for HAL-C gene
selection in
some mammal
and bird
species

14. Protein alignment shows E
(glutamic acid) it’s been replaced by
M (methionine) and Y (tyrosine) and
G (glycine)
Datamonkey 2.0: a modern web application for characterizing selective and other evolutionary processes
Mol. Biol. Evol. 35(3):773–777
Wayne Delport, Art F. Poon, Simon D. W. Frost and Sergei L. Kosakovsky Pond
Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology
Bioinformatics 26(19): 2455-2457
Sergei L. Kosakovsky Pond and Simon D. W. Frost (2005)
Datamonkey: rapid detection of selective pressure on individual sites of codon alignments
Bioinformatics 21(10): 2531-2533