Chapter 8: The Battle of the Sexes

Stick insect  -- virgin birth --- female lay fertile eggs without ever mating with a male and perfectly healthy little stick insects emerge from these eggs. --- chromosomes all came from the mother. For us and out rodent relatives the only way to generate live young is by having DNA from both a mother and a father.  --- insects, fish amphibians reptiles and even birds all have a few species that can reproduce parthenogenetically.

Mammal characteristics --- hair and three bones in or middle ear.

1)     The most primitive examples of mammals--- duck billed platypus and echida --- lay eggs.

2)     Marsupials --- kangaroo and Tasmanian devil

3)     Placental mammal humans tigers mice blue whales eutherian mammals

We cant escape our(evolutionary) past

This battle of the sexes in mammals has reached an evolutionary Mexican stanf-off.

Azim Surani created the mouse zygotes that contained only paternal DNA or only maternal DNA --- all the chromosome had come from the mother, the placental tissues were very underdeveloped. VS. all the chromosomes from the father the embryo was even more retarded but there was much better production of the placental tissues. --- male chromosome pushes the developmental programme in favor of the placenta, whereas a maternally derived genome has less of a drive towards the placenta, and more towards the embryo itself.

All these data suggested that something in the male chromosomes pushes the developmental programme in favor of the placenta, whereas a maternally-derived genome has less of a drive towards the placenta, and more towards the embryo itself.

For chromosome 11, Bruce Cattanach created mice that had inherited two copies from their mother and none from their father, or vice versa. Figure 8.1

There are factors in the paternal chromosomes that push towards development of larger offspring. Factors in the maternal chromosomes either act in the opposite direction or are broadly neutral.

Sex discrimination

Because the two copies of the chromosome behave differently depending on their parent of origin, chromosome 11 is known as an imprinted chromosome. --- only certain stretches of chromosome 11 are imprinted.

Imprinted regions are stretches of the genome where we can detect parent of organ effects on offspring.

In the chromosome 11, genes associated with placental growth are switched on and are very active in the copy of the chromosome inherited from the father, --- this carries risks of nutrient depletion for the mother who is carrying the fetus and a compensatory mechanism has evolved, --- the copies of these same genes on the maternal chromosome tend to be switched off and this limits the placental growth.

Mice insulin like growth factor 2 (Igf2) --- promote embryonic growth, and is normally expressed only from the paternally-derived coy of chromosome 7. ---- when the mutation was passed on from the mother, the young mice looked the same as any other mice. --- this is because the Igf2 gene is normally switched off on the maternal chromosome anyway 

But when mutant Igf2 gene was passed down from father to offspring, the mice in the litter were much smaller than usual.  This was because the one copy of the Igf2 gene that they relied on for strong fetal growth had been switched off by the mutation.

100 imprinted genes in mice and about half this number in human.

Imprinting evolved about 150 million years ago, and it really only occurs to a great extent in placenta mammals.

When imprinting goes bad

Prader-Willi syndrome(PWS)  --- 1/20,000 live births. ---low birth weight, floppy muscles, difficult to feed.

Angelman syndrome(AS)  severe mental retardation, small brain size and very little speech. Laugh spontaneously for no obvious reason. --- happy puppets

abnormal chromosome 15 from father --- PWS  when abnormal chromosome 15 from mother --- AS

Another way in which patients can inherit PWS or AS. ---- uniparental disomy --- one parent contributing two chromosomes. ---- the children have two normal copies of chromosome 15. The trouble is, they’ve inherited both from their mother, and none from their father. -- PWS

AS --- normal copies of chromosome 15 but both from the father.

Gene UBE3A lacked --- no UBE3A  protein in its brain. ----- symptoms of Angelman syndrome.

Paternal SNORD116 gene--- no inherit this region of chromosome 15 from its father --- Prader-Willi syndrome.

Beckwith-Wiedemann syndrome --- over-growth of tissues, over developed muscles including tongue, --- both the maternal and paternal copies of a gene on chromosome 11 get switched on , when normally only paternally-derived version should be expressed. Key gene seems to be IGF2  

Silver-Russell syndrome---- IGF2 protein expression is depressed, and the growth fo the fetus is dampened down.  

Epigenetic imprint

Imprinting refers to a situation where there is expression of only one member of a pair of genes, and the expression may be either maternal or paternal .

If a paternally inherited region of a chromosome is methylated, the paternally derived genes in this region will be repress.

You put your imprint on, you take your imprint off…

1)     The sperm that enters the egg has epigenetic modification on it

2)     The epigenetic modifications get taken off, except at the imprinted regions (in the immediate post-fertilization zygote)

3)     Epigenetic modifications get taken off, including at the imprinted regions (as the primordial germ cells break away from the somatic differentiation pathway)

4)     Epigenetic modifications get put on (as the sperm develops)

This could seem like an unnecessarily complicated way to get back to where we started from, but it’s essential.