Moving to the nucleus .....
Biased transmission of alleles or entire
chromosomes
Segregation distortion (meiotic drive,
selfish DNA)
Gametophytic effects in plants
Biased or unusual patterns of gene
expression
Maternal effect genes
Imprinted genes (parent-of-origin
expression bias)
Paramutation (allelic cross-talk &
silencing)
Transmission bias - meiotic drive,
(segregation distortion, selfish DNA)
Any alteration of meiosis or subsequent
production of gametes that results in the
biased transmission of a particular
genotype
Seen in a wide array of taxa including
plants, insects and mammals
Drive systems can act through male or
female gametes, depending upon the
specific system
Drive systems can be located on
autosomes or sex chromosomes
Drive occurs through a variety of
molecular genetic mechanisms, each a
unique story
Once such mechanisms evolve they
have an extreme selective advantage in
nature – “selfish DNA”
Meiotic drive e.g. Segregation distorter
(SD) system of Drosophila
melanogaster
• Autosomal chromosome 2
• SD = distorter or “driver” allele (dominant,
gain-of-function mutation)
• SD+ = wild-type allele
SD+
SD+
SD
SD+
SD+
SD+
How does this compare with the expected
(Mendelian) result?
[Kusano et al. BioEssays 25:108]
The segregation distorter (SD) system
of Drosophila melanogaster
Which gamete (male or female) is
susceptible to action of the SD driver?
SD+
SD+
Female
Male
Progeny
SD cn+ bw+ /
SD+ cn bw
SD+ cn bw /
SD+ cn bw
50 red eye
SD cn+ bw+
SD+ cn bw
50 white eye
SD+ cn bw
SD+ cn bw
SD+ cn bw /
SD+ cn bw
SD cn+ bw+ /
SD+ cn bw
99 red eye
SD cn+ bw+
SD+ cn bw
1 white eye
SD+ cn bw
SD+ cn bw
Inheritance of the SD chromosome in
drosophila
SD = duplicated, variant
RanGTPase activating protein
(RanGAP)
• Enzymatically active
• Mis-localized to the nucleus
(vs. cytosol)
• RanGTPase functions:
nuclear transport, cell cycle
regulation
Rsp is a noncoding “satellite”
120 bp DNA repeat
• Peri-centric region
• Rsp-i 50 copies
• Rsp-s 500-700 copies
Sperm carrying the SD+ chromosome fail
due to chromosomes behaving badly
• Fail to replace histone with sperm specific
prolamine
• Fail to condense as appropriate for a
sperm nucleus
(Ganetzky, American Scientist 88:128-135)
Current models of SD action
Larracuente & Presgraves, Genetics 192:33
Transmission bias - meiotic drive
(segregation distortion)
Any alteration of meiosis or subsequent
production of gametes that results in the
biased transmission of a particular genotype
Most bias due to post-meiotic events during
gametogenesis
Most systems act through heterozygous
males, but female systems are known
Other examples:
t chromosome of mice: + sperm of t/+
males do not swim > excess of
fertilization by t sperm
X-linked drivers in drosophila: Y
sperm of XY males do not function
> excess of female progeny
X-linked drivers in Silene latifolia XY
males: Y pollen do not function
> excess of female progeny
Transmission bias - gametophytic
effects in plants
1N
1N
mutation block
(Mosher & Melnyk
Trends Plant Sci 15:204)
meiotic drive - any alteration of meiosis or
subsequent production of gametes that
results in the biased transmission of a
particular genotype
Genetic mutations that disrupt function of the
haploid gametophyte (embryo sac or pollen
grain)
• Failed gamete production
• Sex-specific transmission bias against
the mutation
Transmission bias - gametophytic
effects in plants
e.g. seth6 mutation disrupts pollen tube
growth in Arabidopsis:
Pollen of + / + plant:
All four tetrad
members function
4 pollen tubes are
germinating
Pollen of + / seth6
plant:
Only + tetrad (2/4)
members germinate
seth6 pollen fails to
germinate
[Lalanne et al. Genetics 167:1975]
Transmission bias - gametophytic
effects in plants
e.g. seth6 mutation disrupts pollen tube growth
in Arabidopsis:
Organism /
gene
♀
♂
progeny
genotype genotype genotype
Arabidopsis
+ / seth6
seth6
pollen function
+/+
+/+
463
+ / seth6 428
+/ +
+ / seth6
+/+
463
+ / seth6 5
+ / seth6
+ / seth6
What is
expected
here?
Transmission bias - gametophytic
effects in plants
e.g. the cap1 mutation disrupts egg function
in Arabidopsis:
Developing ovules of cap1 / + plant:
+ ovules develop; cap1 ovules abort
[Modified from Grini et al. Genetics 162: 1911]
Transmission bias - gametophytic
effects in plants
e.g. the cap1 mutation disrupts egg function
in Arabidopsis:
Organism /
gene
♀
♂
progeny
genotype genotype genotype
Arabidopsis
cap1
egg function
cap1 / +
+/+
+/+
367
+ / cap1 50
+/ +
+ / cap1
+/+
182
+ / cap1 189
+ / cap1
+ / cap1
What is
expected
here?
[Modified from Grini et al. Genetics 162: 1911]
Moving to the nucleus .....
Biased transmission of alleles or entire
chromosomes
Segregation distortion (meiotic drive,
selfish DNA)
Gametophytic effects in plants
Biased or unusual patterns of gene
expression
Maternal effect genes
Imprinted genes (parent-of-origin
expression bias)
Paramutation (allelic cross-talk &
silencing)
Expression bias - Maternal effect
genes
Not to be confused with maternal inheritance
or maternal environmental effects!
The genotype of the mother determines the
phenotype of the progeny:
Maternal genes produce RNAs and/or
proteins that locate to the egg
Function in early development
Directly influencing phenotype
All the progeny of a single maternal parent
have the same phenotypes, even though
they may have different genotypes!
An important developmental mechanism in
drosophila
A few examples in plants
A growing number of examples in
mammals
Expression bias - Maternal effect
mutations
e.g. Bicoid – maternal effect gene in
drosophila development
Asymmetric environment of egg
development
Maternally produced bicoid mRNA locates
to the anterior of the egg
Translated post-fertilization
Establishes anterior identity of the embryo
(Lawrence, 1992. The Making of a Fly)
Expression bias - Maternal effect
mutations
e.g. Bicoid – maternal effect gene in
drosophila development
maternal parent:
bicoid +/+
normal larva
bicoid – / –
two tails, no head
Partial rescue eggs from bicoid – / – female:
Inject anterior cytoplasm from eggs of bicoid
+/+ female into anterior of eggs from bicoid
– / – female
(Lawrence, 1992. The Making of a Fly)
Maternal effect mutations –
Mendelian genotypes &
non-Mendelian phenotypes!
♀ genotype
♂ genotype
progeny
genotype
progeny
phenotype
bicoid -/-
bicoid +/+
bicoid -/+
all lethal (all
eggs of
bicoid -/- ♀
lack polarity)
bicoid +/+
bicoid -/-
bicoid -/+
all normal
(all eggs of
bicoid +/+ ♀
have normal
polarity)
bicoid +/-
bicoid +/-
bicoid +/+
bicoid +/bicoid -/-
all normal
(bicoid – is
recessive;
all eggs of
+/- ♀ are
normal)
Recover bicoid -/- progeny genotypes in
Mendelian ratios!
All progeny of a maternal parent have the
same phenotype, even though they have
different genotypes!
Expression bias - Maternal effect
mutations
e.g. shell coiling I in Limnaea snail
♀
♂
progeny
genotype genotype genotype
progeny
phenotype
+/+
s/s
+/s
all dextral
(patterned in egg
of +/+ ♀)
s/s
+/+
+/s
all sinestral
(patterned in egg
of s/s ♀)
+/s
+/s
+/+
+/s
s/s
all dextral
(dominant to s)
patterned in egg of
+/s ♀
+ allele dominant for dextral
coiling
s allele recessive for
sinestral coiling
sinestral dextral
A growing number of examples in
mammals
Often identification via molecular studies of
oocytes
Important maternal effect genes and their
proposed roles
Gene name
Gene
symbol
Proposed role
Heat shock factor 1
Hsf1
Embryo cleavage
Nucleoplasmin 2
Npm2
Nucleolar biogenesis
NACHT, L rich
repeat & PYD9containing 5
Nalp5 or Embryo cleavage
MATER
Zygote arrest 1
Zar1
Cleavage
Stem cell enriched
protein
Stella
Embryo development
Zn finger protein 36
like 2
Zfp36l2
Cleavage
Basonuclin
Bnc
Cleavage
[Cui & Kim, Reprod Fertil & Devel 19:25]
Maternal effects in mammals - an
interesting twist? Shells and Heart: Are
Human Laterality and Chirality of Snails
Controlled by the Same Maternal Genes?
[Oliverio et al. Am J Med Genet 152A:2419]
True maternal effect mutations are
rare in plants
e.g. short integument (sin) of Arabidopsis
♀ genotype ♂
genotype
progeny
genotype
progeny
phenotype
sin -/-
sin +/+
sin +/-
all embryos
abnormal
cotyledons
sin +/+
sin -/-
sin +/-
all normal
embryos
sin +/-
sin +/-
sin +/+
sin +/sin -/-
all normal
embryos
True maternal effect mutations, where
diploid maternal genotype governs progeny
phenotype are rare in plants
Gametophytic effects, where haploid female
gametophyte genotype influences
development, are much more common