1. 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)

2. 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”

3. 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+
Figure 1. Segregation distortion in Drosophila melanogaster. A: Males heterozygous for an SD chromosome and an SD+ chromosome carrying the recessive eye color markers cn and bw (which together produce a white-eyed phenotype when homozygous) crossed with homozygous cn bw females, transmit the SD chromosome to almost 100% of the offspring rather than to the expected 50%. The k value for this example would be If females are the heterozygous parents in the cross illustrated, the SD chromosome would be transmitted according to Mendelian expectation. Because there is no recombination in Drosophila males, the cn and bw markers are transmitted as a unit. B: Diagrammatic representation (not drawn to scale) of the genetic components of SD chromosomes and their distribution along the second chromosome. Thin lines represent the euchromatic portion of the chromosome; thick lines represent the centric heterochromatin. The centromere is shown as a solid circle. Sd, the primary locus responsible for distortion is located towards the euchromatic base of the left arm. The upward modifiers of distortion are located at various positions along the chromosome: E(SD) is located in the centric heterochromatin of the left arm, M(SD) in the euchromatic base of the right arm, and St(SD) in the distal tip of the right arm. Rsp, the target of distortion is located in the centric heterochromatin of the right arm. A typical SDþ chromosome carries wild-type alleles of all the distorter elements and a sensitive allele of Rsp. SD chromosomes carry an insensitive Rsp allele.
How does this compare with the expected (Mendelian) result?
[Kusano et al. BioEssays 25:108]

4. The segregation distorter (SD) system of Drosophila melanogaster
SD = distorter (“driver”) allele (dominant, gain-of-function mutation)
SD+ = wild-type allele
SD+
Female
Male
Progeny
SD cn+ bw+ /
SD+ cn bw
SD+ cn bw /
50 red eye
SD cn+ bw+
50 white eye
99 red eye
1 white eye

5. 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-cedntric region
Rsp-i 50 copies
Rsp-s 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: )

6. Current models of SD action
Figure 7 Current models of SD action. (A) Sd–RanGAP directly binds Rsp repeats, disrupting chromatin condensation in Rsps-bearing spermatids causing spermatid dysfunction either as a consequence of disrupted nuclear transport or some other cellular function of RanGAP. (B) Sd–RanGAP disrupts nuclear transport globally, but Rsps-bearing spermatids are disproportionately sensitive to this disruption because large blocks of Rsp act as a sink for chromatin modifiers when their access to the nucleus is limited. (C) Rsp rasiRNAs, presumably required for postmeiotic chromatin condensation, are exported from the nucleus, where they form ribonucleoprotein (RNP) complexes; however, the RNP complexes fail to target chromatin modifiers to the genomic Rsp satellite because of some disrupted RanGAP, or ran-like, function (see text). Although the disruption is shown as a failure to reenter the nucleus due to disrupted transport, a disrupted Ran-GTP/Ran-GDP (or ran-like-GTP/ran-like-GDP) gradient could affect chromatin condensation more directly.
Larracuente & Presgraves, Genetics 192:33

7. 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

8. Transmission bias - gametophytic effects in plants
(Mosher & Melnyk Trends Plant Sci 15:204)
Figure 1. Gametophytic development and fertilization. During gametogenesis, haploid spores in male and female portions of the flower undergo two to three mitotic divisions to generate the maternal megagametophyte (ovule) and paternal microgametophyte (pollen grain). The maternal spore goes through three rounds of mitosis before cytokinesis to generate seven cells including the haploid egg cell (EC) and the homodiploid central cell (CC). The paternal spore first divides asymmetrically to form the large vegetative cell (VC) and smaller generative cell (GC). The generative cell is engulfed by the vegetative cell before a second mitosis occurs to generate two haploid sperm cells (SC) contained within the cytoplasm of the vegetative cell (VC). Fertilization occurs when the vegetative cell grows a pollen tube to deliver the sperm cells to the maternal gametophyte. One sperm cell fertilizes the egg cell and the second sperm cell separately fertilizes the central cell. The fertilized egg cell (fEC) develops into the diploid embryo while the fertilized central cell (fCC) grows to form the triploid endosperm. After an initial proliferative phase the endosperm decays to nourish the growing embryo and does not genetically contribute to the next generation.
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

9. Transmission bias - gametophytic effects in plants
mutation block 1N
(Mosher & Melnyk
Trends Plant Sci 15:204)
Figure 1. Gametophytic development and fertilization. During gametogenesis, haploid spores in male and female portions of the flower undergo two to three mitotic divisions to generate the maternal megagametophyte (ovule) and paternal microgametophyte (pollen grain). The maternal spore goes through three rounds of mitosis before cytokinesis to generate seven cells including the haploid egg cell (EC) and the homodiploid central cell (CC). The paternal spore first divides asymmetrically to form the large vegetative cell (VC) and smaller generative cell (GC). The generative cell is engulfed by the vegetative cell before a second mitosis occurs to generate two haploid sperm cells (SC) contained within the cytoplasm of the vegetative cell (VC). Fertilization occurs when the vegetative cell grows a pollen tube to deliver the sperm cells to the maternal gametophyte. One sperm cell fertilizes the egg cell and the second sperm cell separately fertilizes the central cell. The fertilized egg cell (fEC) develops into the diploid embryo while the fertilized central cell (fCC) grows to form the triploid endosperm. After an initial proliferative phase the endosperm decays to nourish the growing embryo and does not genetically contribute to the next generation.
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

10. 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
Figure 2.— Pollen morphology and in vitro germination efficiency for wild type and seth hemizygotes. (A–C) Mature +/seth6 tetrads stained with DAPI (A), Alexander stain (B), and fluorescein diacetate (C). (D–G) In vitro germination of wild-type (D) and +/seth6 (E) tetrads. (F) Histogram showing the percentage in vitro germination of pollen from wild-type (Ler) and hemizygous seth6, seth7, seth8, seth9, and seth10 plants. The standard error for 12 independent experiments is shown (n = 1200 pollen). (G) Pollen tube lengths of pollen from wild-type (Ler) and heterozygous seth8, seth9, and seth10 plants (n = 200 pollen). The standard error of 4 independent experiments is shown
Pollen of + / seth6 plant:
Only + tetrad (2/4) members germinate
seth6 pollen fails to germinate
[Lalanne et al. Genetics 167:1975]

11. Transmission bias - gametophytic effects in plants
e.g. seth6 mutation disrupts pollen tube growth in Arabidopsis:
Organism / gene
♀ genotype
♂ genotype
progeny genotype
Arabidopsis
seth6
pollen function
+ / seth6
+ / +
+ /
+ / seth6 428
+ / +
+ / seth
What is expected here?

12. 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
Figure 1.—Embryo sac and seed development in cap mutants. (A) Two classes of developing ovules in a cap1/CAP1 silique at 3 DAP as shown by scanning electron micrograph. Bar, 100 J
[Modified from Grini et al. Genetics 162: 1911]

13. Transmission bias - gametophytic effects in plants
e.g. the cap1 mutation disrupts egg function in Arabidopsis:
Organism / gene
♀ genotype
♂ genotype
progeny genotype
Arabidopsis
cap1
egg function
cap1 / +
+ / +
+ /
+ / cap
+ / +
+ / cap1
+ /
+ / cap
What is expected here?
Figure 1.—Embryo sac and seed development in cap mutants. (A) Two classes of developing ovules in a cap1/CAP1 silique at 3 DAP as shown by scanning electron micrograph. Bar, 100 J
[Modified from Grini et al. Genetics 162: 1911]

14. 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)

15. Expression bias - Maternal effect genes
Not to be confused with maternal inheritance!
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 and mammals
Reflects differences in developmental strategies among organisms

16. 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, The Making of a Fly)

17. Expression bias - Maternal effect mutations
e.g. Bicoid – maternal effect gene in drosophila development
Expression bias - Maternal effect mutations
maternal parent:
bicoid +/+ bicoid – / –
normal larva 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, The Making of a Fly)

18. 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)
all normal (all eggs of bicoid +/+ ♀ have normal polarity)
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!

19. Expression bias - Maternal effect mutations
e.g. shell coiling I in Limnaea snail
Expression bias - Maternal effect mutations
♀ genotype ♂
genotype
progeny genotype
progeny phenotype
+/+
s/s
+/s
all dextral (patterned in egg of +/+ ♀)
all sinestral
(patterned in egg of s/s ♀)
all dextral (dominant to s)
patterned in egg of +/s ♀
Example of left- and right coiling in gastropods:
figure at left side: Neptunea angulata as left (sinestral) coiled
figure at right side: Neptunea despecta as right (dextral) coiled.
[Nyst, PH (1878) Conchyliologie des terrains tertiaires de la Belgique. Ann Mus r Hist nat Belg 3:1-262
Scanned by Tom Meijer]
sinestral dextral
+ allele dominant for dextral coiling
s allele recessive for sinestral coiling

20. True maternal effect mutations are rare in plant reproductive biology
e.g. short integument (sin) of Arabidopsis
True maternal effect mutations are rare in plant reproductive biology
♀ genotype
♂ genotype
progeny genotype
progeny phenotype
sin -/-
sin +/+
sin +/-
all embryos abnormal cotyledons
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

21. Maternal effect genes are uncommon in mammals
Recent identification via molecular biology, not genetic mutation
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 & PYD9-containing 5
Nalp5 or MATER
Zygote arrest 1
Zar1
Cleavage
Stem cell enriched protein
Stella
Embryo development
Zn finger protein 36 like 2
Zfp36l2
Basonuclin
Bnc
[Cui & Kim, Reprod Fertil & Devel 19:25]