Lecture 3

  1. 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

  1. 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

  1. 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

  1. Summarize the events that must occur during the process of inactivating an X chromosome.

  2. long non-coding RNA called XIST is expressed from the X-chromosome that will be inactivated, XIST coats chromosome

  3. XIST recruits proteins that can modify histones

  4. histones are changed such that they tightly wrap DNA - no space for transcription or RNA polymerase

  5. changes to histones also include recruiting certain types of histones to inactive X

  6. DNA is methylated at CpG sites in gene promoters → locks in silencing

  7. inactive X goes to periphery of nucleus

    • transcriptionally silent compartments are generally found in periphery

  8. What is a long non-coding RNA?

  • type of RNA - 1kb +

  • does not produce protein

  1. 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?

  2. 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

  3. mutation in the promoter of XIST that affects its expression

    • X expressing more XIST gets selected for inactivation

  4. 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

  1. 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

  1. 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

  1. 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