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 genesImprinted 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

[Kusano et al. BioEssays 25:108]

How does this compare with the expected (Mendelian) result?

• Autosomal chromosome 2• SD = distorter or “driver” allele (dominant,

gain-of-function mutation)• SD+ = wild-type allele

SD+SD+

Female Male Progeny

SD cn+ bw+ / SD+ cn bw

SD+ cn bw /

SD+ cn bw

50 red eyeSD cn+ bw+ SD+ cn bw

50 white eyeSD+ cn bw SD+ cn bw

SD+ cn bw /

SD+ cn bw

SD cn+ bw+ / SD+ cn bw

99 red eyeSD cn+ bw+ SD+ cn bw

1 white eyeSD+ cn bw SD+ cn bw

The segregation distorter (SD) system of Drosophila melanogaster

• SD = distorter (“driver”) allele (dominant, gain-of-function mutation)

• SD+ = wild-type alleleSD+

SD+

Inheritance of the SD chromosome in drosophila

(Ganetzky, American Scientist 88:128-135)

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

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 500-700 copies

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

(Mosher & Melnyk Trends Plant Sci 15:204)

Transmission bias - gametophytic effects in plants

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

1N1N

(Mosher & Melnyk Trends Plant Sci 15:204)

Transmission bias - gametophytic effects in plants

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

mutation block

1N1N

[Lalanne et al. Genetics 167:1975]

Transmission bias - gametophytic effects in plants

e.g. seth6 mutation disrupts pollen tube growth in Arabidopsis:

Pollen of + / + plant:All four tetrad

members function4 pollen tubes are

germinating

Pollen of + / seth6 plant:

Only + tetrad (2/4) members germinate

seth6 pollen fails to germinate

e.g. seth6 mutation disrupts pollen tube growth in Arabidopsis:

Organism / gene

♀ genotype

♂ genotype

progeny genotype

Arabidopsis

seth6

pollen function

+ / seth6 + / + + / + 463

+ / seth6 428

+ / + + / seth6 + / + 463

+ / seth6 5

+ / seth6 + / seth6 What is expected here?

Transmission bias - gametophytic effects in plants

[Modified from Grini et al. Genetics 162: 1911]

Developing ovules of cap1 / + plant:+ ovules develop; cap1 ovules abort

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 / + + / + + / + 367

+ / cap1 50

+ / + + / cap1 + / + 182

+ / cap1 189

+ / cap1 + / cap1 What is expected here?

[Modified from Grini et al. Genetics 162: 1911]

Transmission bias - gametophytic effects in plants

e.g. the cap1 mutation disrupts egg function in Arabidopsis:

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!

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

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

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)

e.g. Bicoid – maternal effect gene in drosophila development

Expression bias - Maternal effect mutations

maternal parent: bicoid +/+ bicoid – / –normal larva two tails, no head

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!

♀ genotype

♂

genotype

progeny 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 ♀

sinestral dextral

+ allele dominant for dextral coiling

s allele recessive for sinestral coiling

e.g. shell coiling I in Limnaea snail

Expression bias - Maternal effect mutations

♀ 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

e.g. short integument (sin) of Arabidopsis

True maternal effect mutations are rare in plant reproductive biology

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

Important maternal effect genes and their proposed rolesGene 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

Embryo cleavage

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]

Recent identification via molecular biology, not genetic mutation

Maternal effect genes are uncommon in mammals