Detection of the footprint
of natural selection in the
genome
Genomics
Advanced Genetics
2015-2016
Noelia Pérez Pereira
Contents
 Introduction
Natural selection
Modes of selection
Detecting natural selection
 Detecting natural selection at macroevolutionary level
Gene-based methods
Other rate-based methods
INTRODUCTION
Natural selection
Mechanisms that explain adaptation of populations to their environment
Beneficial traits (those that improve an individual’s chances to
survive and reproduce) tend to become more frequent in
populations over time.
Vitti et al. (2013)
Natural selection
Mechanisms that explain adaptation of populations to their environment
Beneficial traits (those that improve an individual’s chances to
survive and reproduce) tend to become more frequent in
populations over time.
Vitti et al. (2013)
Natural selection
Mechanisms that explain adaptation of populations to their environment
Beneficial traits (those that improve an individual’s chances to
survive and reproduce) tend to become more frequent in
populations over time.
Vitti et al. (2013)
Modes of selection
Modified from Quintana-Murci & Clark (2013)
Detecting natural selection
Microevolution
Polymorphism data
Divergence data
Macroevolution
Detecting selection at the
MACROEVOLUTIONARY
level
Methods for macroevolution
Vitti et al. (2013)
Gene-based methods
1. Ka/Ks ratio
Ka =
Synonymous changes are assumed to be neutral
non-synonymous changes
non-synonymous sites
Ks =
synonymous changes
synonymous sites
Vitti et al. (2013)
Gene-based methods
1. Ka/Ks ratio
Ka =
Synonymous changes are assumed to be neutral
non-synonymous changes
non-synonymous sites
Ks =
synonymous changes
synonymous sites
Ka / Ks > 1
Ka / Ks = 1
Ka / Ks < 1
Positive selection
Genetic drift
Purifying selection
λ>μ
λ=μ
λ<μ
Gene-based methods
2. McDonald-Kreitman test (MKT)
Positive selection
Pn
Ps
Dn
< Ds
Fixed difference
Polymorphic site
Null hypothesis
Purifying selection
Pn
Ps
Dn
= Ds
Pn
Ps
>
Dn
Ds
Egea et al. (2008)
Gene-based methods
2. McDonald-Kreitman test (MKT)
http://mkt.uab.cat/mkt/
 Single-locus MKT
Standard MKT: coding regions
Advanced MKT: closely linked regions
 Multi-locus MKT
2x2 contingency table
Other rate-based methods
1. Hudson-Kreitman Aguadé (HKA)
Levels of polymorphism and divergence should be correlated (because both are
primarily functions of the mutation rate) unless selection causes one to exceed the
other
D
P
Value
• Diversity within the species is
reduced
ratio
D: fixed interspecific differences
P: within-species polymorphisms
across loci
• Change contributing to speciation
was accelerated
Value
• Balancing selection between species
Vitti et al. (2013)
Other rate-based methods
2. Comparative genomic data
Regions that undergo accelerated change in one lineage but are conserved in
related lineages are probable candidates for selection
Comparative analysis
of 29 mammalian
genomes
5.5% of the human
genome: purifying
selection
(∼1,2% exons)
3.6 millions of
conserved elements
References
Vitti, J. J., Grossman, S. R., & Sabeti, P. C. (2013). Detecting natural selection in genomic
data. Annual review of genetics. 47:97-120.
Quintana-Murci, L., & Clark, A. G. (2013). Population genetic tools for dissecting innate
immunity in humans. Nature Reviews Immunology.13(4):280-293.
Hurst LD. (2002). The Ka/Ks ratio: diagnosing the form of sequence evolution. Trends Genet.
18(9):486.
Egea R, Casillas S, Barbadilla A. (2008). Standard and generalized McDonald-Kreitman test: a
website to detect selection by comparing different classes of DNA sites. Nucleic Acids Res.
36:W157–62.
Lindblad-Toh, K., Garber, M., Zuk, O., Lin, M. F., Parker, B. J., Washietl, S., ... & Ward, L. D.
(2011). A high-resolution map of human evolutionary constraint using 29 mammals.
Nature. 478(7370):476-482.
Thank you for your
attention
Genomics
Advanced Genetics
2015-2016
Noelia Pérez Pereira