Pattern of similarity between Europeans and Neanderthals

Green et al. Science 328, 710 (2010)

Summary of recent human history

Reich et al. Nature 468, 1053 (2010)

Adaptive evolution in human brain development genes

Neutral Balancing Selection Selective Sweep

Gene Trees and Evolutionary Hypotheses

Effect of selection on Tajima’s D

selective sweep

balancing selection

neutral

D = 0

Many low frequency

variants and singletons,D negative

Pairwise differences (k)

increase faster than SD positive

Sampling localities of babblers

Carpentarian barrier

temporalisrubeculus

Tajima’s test of neutrality for 12populations (A-K)

• In this diagram, each letter represents a different population

• Under neutrality, k and s should be equal, as they estimate the same quantity

(Edwards, 1997)

Tajima’s D = (or k) - D

(K same as

The site frequency spectrum under selection and neutrality

Nielsen, Annu. Rev. Genet. 2005. 39:197–218

Neutral polymorphism and divergence

D = 2(low )

t (in generations)

Divergence

Polymorphism = 4Nlow

Polymorphism = 4Nhigh

D = 2(high )

Ratio D/2t /4N

t

The HKA test of selection

• Compares the level of polymorphism within species with the level of divergence between species– Expected level of polymorphism is estimated from the

level of divergence– Ratio of polymorphism to divergence should be the

same for all neutral loci and is set by the mutation rate for a locus

– Level of neutral divergence should be unaffected by occasional selective sweeps

Divergence Between Species at Locus X

VariationWithinSpeciesat Locus X

Frequency-Dependent SelectionBalancing Selection

Adaptive Divergence Selective Sweep

A Prediction of the Neutral Theory of Molecular Evolution

And Departures from Neutrality

NeutralZone

Fixed Poly

Locus 1 50 5

330

HKATest

Locus 2

Hudson Kreitman Aguadétest

Fast/Slowpolymorphism

Adh locus Adh-dup

polymorphism

Fixed Poly

Locus 1 50 5

330

HKATest

Locus 2

16

50

20

13

P < 0.02

Adh

Adh-dup

FFFFSSSS

FastFastFastFastSlowSlowSlowSlow

Adjacent silent sitesin linkage disequilibrium

Distant sites in Linkage Equiluilibrium

The “footprint” of balancing selection at Adh in DrosophilaAdapted from Kreitman and Hudson (1991) Genetics 127:565-82

Effect of selective sweep on linked sites

Behavior of selection statistics around the target of selection

Nielsen, Annu. Rev. Genet. 2005. 39:197–218

Selective sweep in Microcephalin

Zebra Finch: a population genomics model system

N=8N=8

N=8

N=8

N=12

2kb

10 kb

Locus 1Locus 2 Locus 3

Seven ‘locus trios’

Balakrishnan, C.B. & Edwards, S. V. 2009. Genetics 181: 645-660

0

0.005

0.01

0.015

0.02

0.025

0.03

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26

Nu

cleoti

de d

ivers

ity

Balakrishnan, C.B. & Edwards, S. V. 2009. Genetics 181: 645-660

Reduced polymorphism in island finches

13 monomorphic loci in island finches

Australian mainland Timor (island)

Austosomes Z chromosome

= 0.01 = 0.003

Low levels of linkage disequilibrium in mainland birds

LD measured in r2

Enhanced LD in island zebra finches

Balakrishnan, C.B. & Edwards, S. V. 2009. Genetics 181: 645-660

The effect of selection and mutation on levels of variability within and between species

Nielsen, Annu. Rev. Genet. 2005. 39:197–218

A plethora of statistical tests of departures from neutrality