Genetic Linkage

Two pops may have the sameallele frequencies but differentchromosome frequencies.

Conditions for Linkage Equilibrium(Two locus case)

1) Frequency of B is the same on chromosome A and a

2) Frequency of haplotypes AB, ab, Ab, aB can be calculated from allele frequencies A=p, a=q, B=t, and b=s.

f(AB) = pt f(ab) = qs f(Ab) = ps f(aB) = pt

3) Coefficient of linkage disequilibrium (D) = 0

f(AB) x f(ab) - f(Ab) x f(aB) = D

ps x qt - pt x qs = 0

(ranges from -0.25 to +0.25)

Hardy Weinberg Principle for Two Loci

Chromosome frequencies remain unchanged across generations if loci are in linkage equilibria.

If loci are in linkage disequilibria, the chromosome frequencies will move closer to linkage equilibrium each generation.

What Creates Linkage Disequilibrium in a Population?

selection, drift, and population admixture

Effects of Selection on Chromosome Frequencies

ab/ab = body size of value 10each additional A or B adds 1 valuepredators eat all individuals of size 12 or less

65.28%survive

65.28%survive

Freq a = (0.1536 + 0.1536) / .6528)/2

= 0.24

Freq b = (0.0576 + 0.0576) / .6528)/2

= 0.09

Freq ab = .24 x .09 = .02

however!

Locus A and B are in disequilibrium among the survivors

Genetic Drift, followed by selection can cause linkage disequilibrium

Admixture

Combination of Two Different Gene Pools

Recombination Breaks Down Linkage Disequilibria

The rate of decline in LD increases with r

LD declines over time (rate depending on r)

r = D sqrt(pqst)

Concept of Linkage

aA

B b

Meiosis

Law of Independent Assortment

AB

Ab

aB

ab

= 0.25

= 0.25

= 0.25

= 0.25

All allele combinations in gametes

equally probable

A a

B b

Meiosis

Probability of recombination = 0.5

AB

Ab

aB

ab

= 0.25

= 0.25

= 0.25

= 0.25All allele combinations

in gametesequally probable

A aB b Meiosis

Probability of recombination = 0.3

A aB b Meiosis

Probability of recombination = 0.1

AB

Ab

aB

ab

All allele combinations in gametes NOTequally probable

= 0.15

= 0.15

= 0.35

= 0.35

AB

Ab

aB

ab

= 0.05

= 0.05

= 0.45

= 0.45

Linked Loci

All allele combinations in gametes NOTequally probable

Concept: The closer two loci are on a chromosome, the lower the probability of recombination.

Why important?

(1) Affects rate that LD is broken down.

(2) Allows one to determine the linear order of genes on a chromosome (make a genome map).

(3) Maps allow for the localization of genes, mutant phenotypes, and QTL in the genome.

Selection hasan effect on

frequency of Balleles

Selection at a single locus affects other loci under LD

LD among 1504 markerLoci on HumanChromosome 22.(Dawson et al. 2002)

Time (generations)

Link

age

Dis

equi

libria

Decay of LD

Present level

For neutral alleles: Genetic drift is the primary evolutionarymechanism. So:

Indicates alleles at the locus may be under selection.

How does LD help identify genes that may be underpositive natural selection?

If LD is not detectable, indicates that an allele is old.Expect old and frequent alleles, or old and rare alleles,But do not expect young, high frequency alleles.

If LD is detectable, indicates that an allele is young.Expect magnitude of LD is proportional to the age of an allele.

G6PD polymorphismand deficiency

Countries with malariahave highest frequencyof a reduced-activity allele.

Characterized SNPs for G6PD locus of 230 men

Nine different G6PD alleles diagnosed by 11 SNPs

Sabeti et al., 2002

Typed each allele for 14 SNPs outside the G6PD locus

LD is higher for the G6PD-202A allele;suggests positive selection

Probabilitythat 2 randomlychosen “a” chromosomeshave the same snpsacross a physicaldistance

The Evolutionary Biology of Sex

Kiwi Milk weed aphid

There is Amazing Diversity in Reproductive Mode

BlueheadedWrasse

Sexual Reproduction Probably Evolved Early In Life

DandelionTaraxacum officinale

Bdelloid rotifer

Examples of parthenogenesis

What Mode of Reproduction is Better?

An asexual female will have 2x as many grandchildren!

Why Aren’t All Species Asexual?

Because asexual populations accumulate deleterious mutations

Termed: Muller’s Rachet

Possibly leads to extinction

None of the 444 cultures hadhigher fitness than the wild type

Evidence for Muller’s Ratchet: Andersson and Hughes (1996)

Barrett and Charlesworth, (1991)

Eichhornia paniculata

Flower number declined ina natural out crossingpopulation, and heterosiswas observed.

Flower number stayedrelatively constant ina naturally self-fertilizingpopulation

Recombination Breaks the Ratchet

Sex maybe advantageousbecause it can recreatefavorable multilocus genotypes

However, adaptation by this process is only faster in largepopulations

However, Suppression of Recombinationis Important in the Evolution

of Sex Chromosomes

Hypotheses for Short-Term Advantages of Sex

• Recombination allows repair of damaged DNA

• Genetically diverse progeny may outcompete asexual progeny

• Muller’s ratchet

• Deleterious mutations are more easily purged in sexual pops

• Rate of evolution is higher in large sexual populations