Lecture 3

Why does Muller’s ratchet apply to the Y chromosome?

Because large portions of the Y chromosome are inherited as indivisible blocks, leading to the transmission of deleterious mutations.

What is 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

What is a palindrome in the context of the Y chromosome?

Inverted duplicates that allow for gene conversion and local recombination between similar blocks.
Prevents mutations by allowing replacement of defective gene with duplicate that is not mutant on same chromosome

What are the consequences of X inactivation in an XY individual?

There is no X-inactivation

What happens to X chromosomes in an XXX individual regarding inactivation?

Two X chromosomes are inactivated in each cell.

What is the role of XIST in X inactivation?

A long non-coding RNA that coats the chromosome to be inactivated and recruits proteins that modify histones.

How does DNA methylation contribute to X inactivation?

DNA is methylated at CpG sites in gene promoters to lock in silencing of the inactive X chromosome.

List events that must occur during process of X inactivation

XIST is expressed from X that will be inactivated and coast chromosome
XIST recruits proteins that modify histones
Histones wrap DNA tightly - no space for transcription or RNA poly
Changes also recruit certain types of histones to inactivate X
DNA is methylated at CpG sites in promoters → silencing
Inactive X goes to periphery of nucleus

What defines a long non-coding RNA?

A type of RNA that is longer than 1kb and does not produce protein.

What can skew the random nature of X inactivation?

Strong deleterious mutations on X required for cell survival or mutations in the XIST promoter affecting expression.

• more cells inactivate mutant X

• X expressing more XIST gets selected for inactivation

What are two possible reasons that genes on X escape inactivation

Females need greater amount of gene than males
There is a homolog of that gene on the Y chromosome and both sexes express same amount (don’t need to inactivate to obtain equal dosage)

What are histone marks?

Modifications that control how tightly DNA is wrapped around nucleosomes, affecting gene expression.
- more compact wrapping = suppressed expression

What technique is used to evaluate histone mark locations in the genome?

ChIP-seq provides quantitative results at exact locations, while immunofluorescence shows relative brightness of different locations