Why does Muller’s ratchet apply to the Y chromosome?
Muller’s ratchet: any part of the genome inherited as an indivisible block will be required to pass on any deleterious mutations to the next generation
Large portions of Y chromosome are inherited as indivisible blocks to males of next gen, therefore Muller’s ratchet applies
Why are there palindromes on the Y chromosome?
Palindromes (inverted duplicates) allow for gene conversion
Local recombination between similar blocks
Intrachromosomal gene conversion replaces a defective gene with duplicate that is not mutant on the same chromosome
prevents mutations
What happens with respect to X inactivation in an XY individual? An XXX individual?
No X-inactivation in an XY
Two Xs are inactivated in each cell of XXX individual
Summarize the events that must occur during the process of inactivating an X chromosome.
long non-coding RNA called XIST is expressed from the X-chromosome that will be inactivated, XIST coats chromosome
XIST recruits proteins that can modify histones
histones are changed such that they tightly wrap DNA - no space for transcription or RNA polymerase
changes to histones also include recruiting certain types of histones to inactive X
DNA is methylated at CpG sites in gene promoters → locks in silencing
inactive X goes to periphery of nucleus
transcriptionally silent compartments are generally found in periphery
What is a long non-coding RNA?
type of RNA - 1kb +
does not produce protein
What two things can skew the random nature of X inactivation and make it more likely that a person’s cells will all have the same inactivated X?
strong deleterious mutation on one X required for cell survival → cells that inactivate normal X might die or be at a competitive disadvantage
more cells inactivate mutant X
mutation in the promoter of XIST that affects its expression
X expressing more XIST gets selected for inactivation
What are two possible reasons that genes on the X escape inactivation?
females need a greater amount than males of that gene
there is a homolog of that gene on the Y chromosome and both sexes express the same amount
don’t need to inactivate to obtain equal dosage
What are histone marks and how are they associated with gene expression?
marks are modifications that control how tightly DNA is wrapped around nucleosome - 9 different types (so far)
more compact wrapping = suppressed expression (TFs cannot access DNA)
less compact = increased expression
What type of experiment is used to assess the amount and locations of a particular histone mark in the genome?
ChIP-seq → quantitative results at exact locations in genome
immunofluorescence → location of brithness
What mechanism causes CpG’s to be lost if they are not close to a gene promoter?
5 mC deamination
CpG sites far from gene promoter tend to be methylated
when cytosine is spontaneously deaminated it is converted to uracil → usually is repaired
in 5mC deamination, U is converted to thymine making a G-T
loss of a CpG
highly error prone