Organelle Inheritance

Linkage and Recombination

9/16/24
Linkage Notation and Linkage analysis

• Terminology
• Uniparental Inheritance
• Linkage
• Parental type
• Recombinant
• Linked, unlinked, unknown linkage
• Map unit (mu)
What is the likely mode of inheritance in this pedigree?
Extra Chromosomal Inheritance
Organelle genomes
Pattern of inheritance in organelles

• Cytoplasmic inheritance
• Mitochondria and chloroplasts organelles present in the cytoplasm
• Present in males and females
• Uniparental inheritance
• Usually only one parent is responsible for the inheritance
• Usually, the maternal parent since in most organism the cytoplasm of the zygote is
inherited from the maternal parent
• Traits exhibit extensive phenotypic variation
• The inheritance of these organelles is not dependent on mitosis or meiosis
but are duplicated and randomly distributed into each daughter cell
• Rare human disease do show cytoplasmic inheritance
• These disorders arise from mutations in the genes within the mtDNA
Sites of mtDNA mutations in certain human diseases

We will skip polygenic inheritance and hybrid vigor.

Independent Assortment versus Linkage

• Linked genes are inherited together:

• modified Mendelian ratios
• Linked genes are separated by crossing over
• effect on gametes and on linkage
• constant for one gene pair (0.001% to 50%)
• Random incidence, a few per meiosis per chromosome
• Linear map for each chromosome (linkage group)
• Linkage map predicts linkage for all crosses
Linked genes do not assort independently
Arrangement of the alleles on the chromosome(s) is critical
for determining the outcome of a cross
Linkage relationship unknown
A/a B/b or Aa • Bb

Unlinked genes
d d D D
A/a; D/d
or Aa; Dd

Linked genes
AB/ab or Ab/aB

A
A
a
a
For genes independently assorting (on
different chromosomes, what is the
frequency of these gametes?

¼
¼
¼
Phenotypes of the offspring from a testcross directly reveal the
gametic genotypes of the dihybrid

• for unlinked genes, parental and

recombinants are produced in a 1:1:1:1
ratio
• 50% of offspring are parental
• 50% of offspring are recombinant

testcross of A/a; B/b x a/a; b/b:

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

1:1:1 :1
 Linked Genes-
Closely linked genes break the rule of
independent assortment
Closely linked genes

½ of gametes will be AB

½ of gametes will be ab
Closely linked alleles break the rule of independent
assortment
• Alleles that are closely linked
Po AB/AB x ab/ab on the same chromosome
segregate together in dihybrid
crosses
F1 AB/ab
• Segregation frequency is like
testcross of F1 AB/ab x ab/ab: single alleles in a monohybrid
AB Ab aB ab
cross – strictly linked
ab AB/ab Ab/ab aB/ab ab/ab • Segregation frequency in
dihybrid is like single alleles in
1: 0: 0: 1
a monohybrid cross
parental recombinants parental

Expect a 1 : 1 assortment of
parental genotypes in gametes
Closely linked alleles break the rule of independent
assortment
• Alleles that are closely linked
Po AB/AB x ab/ab on the same chromosome
segregate together in dihybrid
crosses
F1 X F1 AB/ab X AB/ab
• Segregation frequency is like
F2 single alleles in a monohybrid
½AB ½ab
cross – strictly linked
½AB • Segregation frequency in
½ab dihybrid is like single alleles in
a monohybrid cross
Closely linked alleles break the rule of independent
assortment
• Alleles that are closely linked on
Po AB/AB x ab/ab the same chromosome segregate
together in dihybrid crosses
F1 X F1 • Segregation frequency is like
AB/ab X AB/ab
single alleles in a monohybrid
F2 cross – strictly linked
½AB ½ab
• Segregation frequency in dihybrid
½AB ¼ A B/A B ¼ A B/a b is like single alleles in a
½ab ¼ ab/ A B ¼ a b/a b monohybrid cross

Phenotypic ratio of ¾ A B to ¼ a b
Closely linked alleles break the rule of independent
assortment
• Alleles that are closely linked
Po AB/AB x ab/ab on the same chromosome
segregate together in dihybrid
crosses
F1 AB/ab
• Segregation frequency is like
testcross of F1 AB/ab x ab/ab: single alleles in a monohybrid
AB Ab aB ab
cross – strictly linked
ab AB/ab Ab/ab aB/ab ab/ab • Segregation frequency in
dihybrid is like single alleles in
1: 0: 0: 1
a monohybrid cross
parental recombinants parental

Expect a 1 : 1 assortment of
parental genotypes in gametes
Linkage with crossovers versus
independent assortment
 Non-sister chromatids break and join reciprocally
at Meiosis division I, creating a ‘crossover’

• After a crossover, a single meiosis yields both parental and recombinant type
gametes
• Crossing over: reciprocal recombination at prophase I of meiosis (tetrads) –
homologous recombination
• Crossover points can be observed as chiasmata
• Crossover frequency between alleles depends on the distance between them
Linked genes segregate differently
after a crossover event
For linked genes, recombination frequencies are less
than 50%
• Recombination frequency: calculated
using the frequency of both reciprocal
products of recombination.
• Sum of all recombinant gametes
• The % of recombinant chromosomes is
characteristic of each gene pair and
mainly reflects gene-gene distance
• Recombination frequency is calculated by
• Determining the percent of
recombinants produced.
• Summing the # of recombinant
progeny/Total progeny X 100%
Recombination frequency can be used to demonstrate linkage

Morgan was examining double mutants affecting eye

color and wing size and crossed pr+ ∙ vg+ x pr ∙ vg to
generate dihybrid:
✓ pr+ - red eyes (wild type; dominant) pr - purple eyes
✓ vg+ - normal wings (wild type; dominant) vg – short
(vestigal) wings
Morgan’s testcross (dihybrid x recessive homozygote):
Thomas Hunt Morgan
pr+/pr . vg+/vg x pr/pr . vg/vg

gamete frequencies inferred from

testcross:
pr+ . vg+ 1339 47.2% parental
pr . vg 1195 42.1% parental
pr+ . vg 151 5.3%
10.7%
. +
pr vg 154 5.4% recombinants
total 2839
 Morgan hypothesized pr and vg are linked
gamete frequencies inferred from
- parental pr and vg alleles
testcross: segregate together most of the
time
pr+ . vg+ 1339 47.2% parental
pr . vg 1195 42.1% parental - but at some frequency (R = #
recombinant gametes/total
pr+ . vg 151 5.3%
gametes scored = 10.7%),
pr . vg+ 154 5.4% recombination occurs between
total 2839 these alleles during meiosis
- The % of recombinant
chromosomes (R) is
characteristic of each gene pair
and mainly reflects gene-gene
distance
- A testcross gives %
recombination directly
 Map distance between genes
gamete frequencies inferred from
testcross:
pr+ . vg+ 1339 47.2% parental
pr . vg 1195 42.1% parental
pr+ . vg 151 5.3%
pr . vg+ 154 5.4%
total 2839

• Linkage groups can be arranged on linear genetic maps, with one

map unit (centiMorgan) = distance between two genes with R =1%.
• Distance between pr and vg is 10.7 mu.
• Recombination maps can be used to generate maps of
chromosomes
 Review: recombination frequency in testcross
indicates whether genes are linked or unlinked

testcross
pr+/pr . vg+/vg x pr/pr . vg/vg
dihybrid tester

Cause of Frequency of Description gamete frequency

recombination recombination P:R:R:P

Independent 50 unlinked 1:1:1:1

assortment
Crossovers 0 < R < 50 partially linked < 1: > 0 : > 0 : <1

Linkage 0 strictly linked 1:0:0:1

Summary of Linkage Analysis via Testcross

• Unlinked genes (located on different chromosomes)

• Equal proportions of both parental types and two recombinant types are
produced
• Independent Assortment- Frequency of Recombination = 0.5
• Linked genes do not assort independently
• Completely linked genes (no crossing over)
• Only parental progeny produced
• Frequency of Recombination = 0
• Linked genes with some crossing over between the genes
• More parental types are produced than recombinants progeny
• Frequency of recombination 0 < R < 0.5
• Recombination frequency is calculated by summing the # of
recombinant progeny/ Total progeny X 100%
Gene Mapping with Recombination Frequency

• Genetic Maps
• “distances” between genes related to recombination
frequency
• crossover events are random across the chromosome
• map units (m.u.), 1 m.u. = 1% recombination
• genetic distances measured with recombination
frequencies are approximately additive
• Physical Map
• Using physical distances
• number of base pairs
Genetic Map

• Distance between A to B is 5 m.u.

• Distance between B to C is 10 m.u.
• Can we draw a map of these three genes?
• The order could be A—B----—C
• Or
• The order could be C—A—B
Genetic Map
• Distance between A to B is 5 m.u.
• Distance between B to C is 10 m.u.
• Can we draw a map of these three genes?
• Distance between A to C is 15 m.u.
15 m.u.

A 5 m.u. B 10 m.u. C

• Distance between A to D is 8 m.u.

What is the order of these four genes?
A to D 8 m.u.
23 m.u.
13 m.u.

8 m.u. 5 m.u.
D A B 10 m.u. C

• A to D 8 m.u.
• B to D 13 m.u.
• C to D 23 m.u.
Generating genetic maps of
chromosomes
• Number of linkage groups = Number of chromosomes
• Combining many two gene crosses will yield a complete
chromosome map
• Very labor intensive
• In the next lecture, you will learn how to analyze three gene
crosses which makes mapping easier.