Linkage, Crossing Over and Chromosome Mapping In

Eukaryotes

Exceptions to Mendelian Principle of Independent Assortment

• W. Bateson, R.C. Punnett – sweet pea, flower color and pollen length– P: red, long x white, short– F1: red, long– F2: 24:1:1:7 ????Red, long - 583; white, short – 170 ; parentalRed, short –26; white, long – 24; nonparental

Location of Mendel’s Genes

Trait Phenotype Alleles Chromosome

Seed form round-wrinkled R-r 7

Seed color yellow-green I-i 1

Pod color green-yellow Gp-gp 5

Pod texture smooth-wrinkled V-v 4

Flower color purple-white A-a 1

Flower location axial-terminal Fa-fa 4

Plant height tall-dwarf Le-le 4

Linked Genes

• Thomas Morgan, Alfred Sturtevant, 1911• Cross: two genes located on X-chromosome• y – yellow body; y+ - wild type, gray body • w – white eyes; w+ - wild type, red eyes• P: yyww x y+w+/Y• F1 – all females wild type, all males – mutant

phenotype• F2 – 98.7% parental phenotypes, 1.3% -yellow

body, red eyes or gray body, white eyes

Chromosome Mapping• The frequency of exchange could be taken as an estimate of

the relative distance between two genes along the chromosome

• Exchange occur due to recombination between loci during meiosis

• Non-parental gametes – recombinant gametes• Recombination frequency

RF = # recombinants / #total • Distance between two loci –

R = (# recombinants / #total ) x 100 = distance in cM (now mu – map units)

Chromosome Mapping

• 1% recombination between two genes equals one map unit – centiMorgan, cM

• Sturtevant, Bridges, 1923 – recombination is not restricted to X-linked genes

• In Drosophila, recombination occur only in females, not in males

• Confirmed the chromosomal theory of inheritance

Single Crossovers

• The closer are genes on the chromosome, the less likely it is that any single crossover event will occur between them

• The farther apart two linked genes are, the more likely that a random crossover event will occur

• At the distance > 50%, linkage cannot be determined – genes behave as unlinked

Crossing-over (CO)

• Breakage and rejoining of homologous DNA double helices

• Occurs only between nonsister chromatids at the same precise place – not really

• Visible in diplotene as chiasmata• Occurs between linked loci on same chromosome

– Cis (coupling): recessive alleles on same homolog (AB/ab)

– Trans (repulsion): recessive alleles on different homologs (Ab/aB)

Distance Between Two Linked Genes

• Grey and yellow body y+ and y• Wild type and white color of the eyes – w+

and w• Cross yy ww x y+w+ Y;

– then yy+ ww+ x yw YResults: yellow, white –490; wild type – 497;

yellow – 8; white - 5

Distance between three linked genes

• Grey and yellow body y+ and y• Wild type and white color of the eyes – w+

and w• Miniature - short wings vs wild type

Genetic Map

Figure 5-4 Copyright © 2006 Pearson Prentice Hall, Inc.

Independent assortmentConsequence of independent alignment of

chromosomes in meiotic bivalents

A/A ; B/B a/a ; b/b

A/a ; B/b

¼ A ; B P¼ A ; b R¼ a ; B R¼ a ; b P

OR

Alternate bivalants

A

Bb B

a aA

b

Alternate bivalents

Recombination• Creating new combinations of two or more pairs of

alleles

A/aB/b

a/ab/b

A/AB/B

AB

ab

AB

ab

Ab

aB

parental (P) genotypes recombinant (R) genotypes

parental genotypes

meiosis meiosis

meiosis

Independent assortment• For genes on different (nonhomologous) pairs of

chromosomes, recombinant frequency is always 50%

A/A ; B/B a/a ; b/b

A/a ; B/b

¼ A ; B P¼ A ; b R¼ a ; B R¼ a ; b P

A/A ; b/b a/a ; B/B

A/a ; B/b

¼ A ; B R¼ A ; b P¼ a ; B P¼ a ; b R

50%

recombinants

Figure 5-1a Copyright © 2006 Pearson Prentice Hall, Inc.

Figure 5-1b Copyright © 2006 Pearson Prentice Hall, Inc.

Figure 5-1c Copyright © 2006 Pearson Prentice Hall, Inc.

Crossing Over Is a Physical Exchange Between Chromatids

• That crossing over was the result of an exchange of genetic information between homologous chromosomes was definitively shown by the experiments initially performed by Harriet Creighton and Barbara McClintock (1931).

• They used a combination of genetic and cytological evidence in their proof.

Crossing Over Is a Physical Exchange Between Chromatids

• Used corn chromosome 9 markers: – c = colorless seed – wx = waxy endosperm

• Created a heterozygote with the following characteristics: – Repulsion configuration of genetic markers – Cytological landmarks on both ends of one

chromosome

Creighton and McClintock Experiment

• Chromosome 9– Large chromosome with 1:2 ratio in arms– Short arm possesses a large knob vs small and

no knob– Long arm carries translocation of chr 8 that

broke the arm near centromere– knob – Yg – C - Sh – Wx –translocation parent– Crossed to a plant knobless yg-c-sh-wx-normal

Linkage Problem

• In corn, gene C – colored seed, c – colorless• Gene S – full endosperm, s – shrunken• A true-breeding colored, full-seeded plant is

crossed with a colorless, shrunken-seededF1 - ?F1 plants test-crossed

Linkage Problem

Colored, full – 4,032colored, shrunken – 149colored, full – 152colorless, shrunken – 4, 035Total 8,368

Linkage Problem

Parental: colored, full 4,032 colored, shrunken 4, 035

Total 8,067Nonparental: colored, shrunken 149

colorless, full 152Total 301Rf: ____________________________________________If genes in repulsion?