Linkage and Crossing Over

AGB121

Dept. Of Animal Genetics & Breeding

Veterinary College, Hebbal, Bangalore

Terminologies to Know

• Linkage• Crossing over• Chiasma• Recombination• Gene mapping• Interference

Dr R Jayashree, Asst. Professor(AGB)

Linkage

• 2 genes on separate chromosomes assort independently at meiosis.

• 2 genes far apart on the same chromosome can also assort independently at meiosis.

• 2 genes close together on the same chromosome pair do not assort independently at meiosis.

• A recombination frequency << 50% between 2 genes shows that they are linked.

Dr R Jayashree, Asst. Professor(AGB)

Gene linkage was explained through fruit flies

• Morgan found that linked traits are on the same chromosome.

• Chromosomes, not genes, assort independently during meiosis.

Wild type Mutant

Dr R Jayashree, Asst. Professor(AGB)

Testcross to show that two genes are linked

When there is crossoverDr R Jayashree, Asst. Professor(AGB)

Complete Linkage: P1 Cross

In completelinkage onlyparentalgametes form

hvbw

hvbw

bwhv

bwhvP

:1

F1:bwhv

bwhv

Brown eyes –bwRed eyes –bw+Thin veins- hv+Heavy veins-hv

Dr R Jayashree, Asst. Professor(AGB)

Dr R Jayashree, Asst. Professor(AGB)

Crossing-over

Crossing-over is the reciprocal exchange of homologous chromatid segments of non-sister chromatid, involving the breaking and rejoining of DNA.

Dr R Jayashree, Asst. Professor(AGB)

Mechanism of Crossing-Over

Dr R Jayashree, Asst. Professor(AGB)

The relationship between crossing-over and map distanceDr R Jayashree, Asst. Professor(AGB)

Chiasma

A chiasma (plural chiasmata) represents the physical manifestation of a chromosomal crossover event

Dr R Jayashree, Asst. Professor(AGB)

Recombination

Crossing-over is the event leading to genetic recombination between linked genes in both prokaryotes and eukaryotes.

Recombinant gametes

Dr R Jayashree, Asst. Professor(AGB)

No Linkage-Independent Assortment

Linkage with Recombination

Linkage without Recombination

Creates only parental (noncrossover) gametes.

creates parental gametes and recombinant (crossover) gametes.

Dr R Jayashree, Asst. Professor(AGB)

Single Crossovers: Non-crossover (Parental) and Crossover (Recombinant) Gametes

Dr R Jayashree, Asst. Professor(AGB)

Progeny of single and double crossovers when two genes are linked

Dr R Jayashree, Asst. Professor(AGB)

Double Crossovers

Dr R Jayashree, Asst. Professor(AGB)

Types of Double Exchanges:Not All are Detectable

Dr R Jayashree, Asst. Professor(AGB)

Consequences of a double crossover in a triple heterozygote for three linked genes

Dr R Jayashree, Asst. Professor(AGB)

Rearrangement of the three genes to p j r

Dr R Jayashree, Asst. Professor(AGB)

Crosses of Two X-linked genes

Expect only parental types if no crossing over occursDr R Jayashree, Asst. Professor(AGB)

Dr R Jayashree, Asst. Professor(AGB)

Linkage Maps

Linkage maps/ Chromosome maps show the relative locations of genes on a chromosome determined from recombination rate

• Interlocus distance is proportional to the degree of crossing over between.

– Little or no crossing over in close genes.

– Frequent, even multiple crossovers between distant genes

Dr R Jayashree, Asst. Professor(AGB)

Morgan and Sturtevant (1913) used recombination frequencies to make a genetic map.

A 1% crossover rate is a genetic distance of 1 map unit (mu).

A map unit is also called a centimorgan (cM).

1% crossing over = 1 map unit (in humans 1mu = 1 million bp)

Dr R Jayashree, Asst. Professor(AGB)

Linkage maps estimate distances between genes

• The closer together two genes are, the more likely they will be inherited together.

• Cross-over frequencies are related to distances between genes.The higher the frequency, further the genes are apart

Dr R Jayashree, Asst. Professor(AGB)

Dr R Jayashree, Asst. Professor(AGB)

Three-point mapping, showing the testcross used and the resultant progeny

Dr R Jayashree, Asst. Professor(AGB)

Rewritten form of the testcross and testcross progeny based on the actual gene order p j r

c/o between j and r =22+22+4+2/500 =50/500 = 10%

c/o between p and j =52+46+4+2/500 =104/500 = 20.8%

Dr R Jayashree, Asst. Professor(AGB)

Interference

• Crossovers in adjacent chromosome regions are usually not independent. This interaction is called interference.

• A crossover in one region usually decreases the probability of a crossover in an adjacent region.

tsrecombinan double of # expected

tsrecombinan double of # observed1ce(I)Interferen

Dr R Jayashree, Asst. Professor(AGB)

Genetic Map of Drosophila melanogaster

Dr R Jayashree, Asst. Professor(AGB)

Morgan’s experimental crosses of white-eye and miniature-wing variants of Drosophila melanogaster

Dr R Jayashree, Asst. Professor(AGB)

In an individual heterozygous at two loci, there are two arrangements of alleles:

1. The cis (coupling) arrangement has both wild-type alleles on one homologous chromosome, and both mutants on the other

(e.g., w+ m+ and w m).w+ m+

w m

2. The trans arrangement has one mutant and one wild type

on each homolog (e.g., w+ m and w m+).

w+ m

w m+

Dr R Jayashree, Asst. Professor(AGB)

• Cross-over frequencies can be converted into map units.

• Ex: A 5% cross-over frequency equals 5 map units.

–gene A and gene B cross over 6.0 percent of the time

– gene B and gene C cross over 12.5 percent of the time

– gene A and gene C cross over 18.5 percent of the time