Population Genetics

Evolution depends upon mutation

to create new alleles.

Evolution occurs as a result of population

level changes in allele frequencies.

What evolutionary forces alter

allele frequencies?

How do allele frequencies changein a population from generationto generation?

Hardy-Weinberg Principle

(1) Allele frequencies in a population will not change, generation after generation.

(2) If allele frequencies are given by p and q, the genotype frequencies will be given by p2, 2pq, and q2.

When none of the evolutionary forces (selection, mutation, drift, migration, non-random mating) are operative:

Allele frequencies in the gene pool:

A: 12 / 20 = 0.6a: 8 / 20 = 0.4

Alleles Combine to Yield Genotypic Frequencies

Our mice grow-up and generate gametesfor next generations gene pool

Allele frequency across generations: A General Single Locus, 2 Allele Model

Freq A1 = pFreq A2 = q

Inbreeding Decreases the Frequencyof Heterozygotes

Inbreeding can reducemean fitness by“revealing” deleteriousrecessive alleles.

Inbreeding Depression in Humans

Inbreeding coefficient (F) = Probability that two alleles are identical by descent

AB

0.5

0.5

0.5

(0.5)4 = 0.0625

A

0.5

A

AA

AB

0.5

0.5

0.5

(0.5)4 = 0.0625

B

0.5

B

BB

0.0625 + 0.0625 = 0.125

What is F for an individual of half sib parents?

Box 9B, Figure 1(2) Change of Genotype Frequencies by Inbreeding

Heterozygosity inan inbred population =

Heterozygosity in arandom mating

population

Prob. not IBD

H F = HO (1 - F)

Anytime F is greater than 0, the frequency of heterozygotes islower in an inbred population than in a random mating population.

x

Heterozygosity and Inbreeding

Box 9B, Figure 2. Change of Genotype Frequencies by Inbreeding

9.10 Inbreeding depression in humans

9.11 The golden lion tamarin is a small, highly endangered Brazilian monkey

9.12 Population decline and increase in an inbred population of adders in Sweden

Inbreeding increases egg failure in Parus major

Can organisms avoid inbreeding depression?

Mate ChoiceGenetic Incompatibility

Dispersal

Why did fitness decreaseafter early efforts wereimplemented to conserve remnant populations?

Prairie chicken almost went extinctin the 1950’s.

Average number of nDNA alleles per locus

Illinois Illinois Other Pops in pre-bottleneck present Midwest

5.12 3.67 5.33-5.88

Loss of HabitatExtinction or reduced population sizes

Gene Flow - reduced / eliminated

Genetic Drift and Non-random MatingLoss of heterozygosity

Deleterious alleles increase in frequency

Inbreeding Depression -- lowered fitness

Extinction or reduced population sizes

Measuring Genetic Variation in Natural Populations

Historical Method: Examining protein variation via electrophoresis

Modern Method: DNA sequencing and typing

TTCTTCAGGGGAGGGGGTGGAANATAAAAACAAAAACCCTACAATGTATATTCATCGCCCATAATCGGCTACTTAGACA

More than one allele at 30-50% of all loci in a population.Such loci are called polymorphic.

LDH-B cline in Fundulus

Most populations harbor considerable genetic diversity

Heterozygosity0.10 0.20 0.30

Heterozygosity has a couple of interpretations:

1) Average percentage of loci that are heterozygous per individual.

or

2) Average percentage of individuals that are heterozygous per loci.

Polymorphism

Polymorphism: when two or more alleles at a locus exist in a population at the same time.

Nucleotide diversity:

= xixjijij

Seq 1 G A G G T G C A A C 0.4Seq 2 G A G G A C C A A C 0.5Seq 3 G A G C T G G A A G 0.1

1 2 31

2 0.2

3 0.3 0.5

Freq(x)

(0.4)(0.5)(0.2) + (0.4)(0.1)(0.3) + (0.5)(0.1)(0.5) = 0.077

considers # differencesand allele frequency

In Theory:

Under infinite-sites model: Expectation (

4Ne = frequency of heterozygotes per nucleotide site

Nucleotide diversity is low in humans

Average nucleotide diversity per site across loci

ATCCGGCTTTCGAK = 3 for-->ATCCGAATTTCGA

ATTCGCCTTTCGA

K= Number of segregating (variable) sites in a sample of alleles.

Polymorphism is also estimated by:

Expectation (K

In Theory:

Where a = 1 + 1/2 + 1/3 +……..1/n-1

(75 x 2) + (24) / (102 x 2) = 85.3

75/102 + 1/2 (24/102) = 85.3

Counting alleles

or

Genotypic frequencies

Sequencing Studies Have Revealed Enormous Genetic Diversity

CFTR Locus

Measuring Genetic Variation in Natural Populations

Other Methods:

EST approach

AFLPs

Microsatellites

AAAAAAAA

TTTTTTTTT

Exon3` UTR

An EST is a tiny portion of an entire gene

TTTTTTTTT

ContextualRegion

PolymorphicRegion

Figure 4. Venn diagram of BLAST comparisons among amphibian EST projects. Values provided are numbers of reciprocal best BLAST hits (E<10-20) among quality masked A. mexicanum and A. t. tigrinum assemblies and a publicly available X. tropicalis EST assembly.

A. mex. 7909

A. t. tig. 69122296

523

X. trop.34,296

465 353

A. mexicanum16214 bp

Unseq

UnseqUnseq

Unseq

UnseqUnseq

Unseq

12S rRNA16S rRNAND1ND2

cox 1cox 3ATP6 cox 2ATP8

ND5

cyt b

A. tigrinum15967 bp

D-loopUnseq

Unseq

12S rRNA16S rRNAND1ND2

cox1cox2ATP8ATP6cox3ND3ND4LND4

ND5cyt b

EST Projects: A quick way to obtain complete mtDNA genome sequence.

Mt DNA : 22 tRNAs, 2 rRNAs, 13 mRNAHomoplasmic, maternal transmission, evolves quicklyApproximately 1-2% sequence divergence / million years

0

1

2

3

4

5

6

7

0 500 1000 1500 2000

EST Length (bp)

# SNPs

# SNPs per EST

A. mexicanum A. t. tigrinum

~ 5% mtDNA sequence divergence

Microsatellites

See Figure 3.19 for pict showing gel separation of microsat alleles

Co-dominant marker typeFound in essentially all genomesEvolve at a very high rate (10-3 - 10-4 per locus per gamete per generation)

A A T C C T A G T A T A T A

T T A G G A T C A T A T A T G T G C T T A A

5’ 3’

T T A G G A T C A T A T A T G T G C T T A A

A A T C T A T A T A C A C G A A T T 5’ 3’

TA

A GTC

Replication inserting TA

A A T C T A T A

T T A G G A T C A T A T A T G T G C T T A A

5’ 3’

TA

A GTC

Insertion during DNA replication

A A T C C T A G T A T A T A

T T A G G A T C A T A T A T G T G C T T A A

5’ 3’

A A T C C T A G T A T A T A

T T A G A T A T G T G C T T A A

5’ 3’

GA

TAT C

Mispairing of DNAduring replication

A A T C C T A G T A T A C A C G A A T T

T T A G A T A T G T G C T T A A

5’ 3’

GA

TAT C

T A is excised

Replication of DNA

Deletion during DNA replication

A A T C C T A G T A T A T A C A C G A A T T

T T A G G A T C A T A T A T G T G C T T A A

5’ 3’

A G

A A T C T A T A T A C A C G A A T T

T T A G G A T C A T A T A T G T G C T T A A

5’ 3’

TA

TC

Excision and repair inserts TA

G T

A A T C T A T A C A C G A A T T

T T A G G A T C A T A T T T A A

5’ 3’

TA

A GTC

AT

CG

Slipped-strand mispairing

Insertion in non-replicating DNA

AFLP (Amplified Fragment Length Polymorphisms)

RD of DNA

Ligation of adaptorscreates PCR primerrecognition sequence

Subsequent selective PCRallows sampling of for

restrictionlength polymorphisms

E M M

Allele 1

E M

Allele 2

AFLP Gel

Representative Molecular Approaches Genetic/Phylogenetic Resolution vs Appropriateness

Clonality Parentage Populations Species

Restriction Fragment Analysis * * ** ***

DNA sequencing/typing overkill overkill *** ***

mt DNA na na ** ***

AFLPs * * * *

Microsatellites *** *** ** na

From Avise’s book