genome organisation- 4 lectures

Question 1

key features of bacterial genomes

Answer 1

-short, often overlapping genes because of this- reliance on alternative splicing for proper gene expression
-higher levels of protein coding genes
-relatively few transcription start sites

Question 2

eukaryotic genome features

Answer 2

much lower percentage of coding genes, stuff like repetitive sequences and structural DNA more common- bc it’s harder to store large volumes of DNA, less selection pressure on small genome

Question 3

an average human gene consists of:

Answer 3

○ 4 exons
○ 1000bp CDS
○ 20kbp genomic footprint
○ 95% intron

Question 4

percentage of the human genome which is transcribed into RNA

Answer 4

5%- 1% of that is mRNA

Question 5

centromere features

Answer 5

5 million bp, consists of repeats called α-satellites

Question 6

telomere features

Answer 6

10k bp long, made of short repeats, 1% of the total genome

Question 7

types of repetitive DNA

Answer 7

satellites- short repeats
retrotransposons- larger regions which move themselves around the genome- LTRs, LINEs, SINEs, these make up around 30% of an average gene

Question 8

why is studying repetitive DNA useful to us?

Answer 8

repetitive DNA is useful for studying population genetics and conservation

Question 9

example of an organism with weird genome organisation

Answer 9

trypanosomes- 10k genes, with unusually few promoters- genome made up of transcriptional ‘units’
reliance on splicing, gene regulation happens post-translationally

Question 10

viral 3D genome organisation

Answer 10

generally not that compact, genes fitting inside a virion

Question 11

length/diameter ration for virus vs bacteria

Answer 11

100 vs 1500 (bacteria)

Question 12

bacterial genome features

Answer 12

more organised than viral- in a nucleoid in the middle of the cell, folded up nicely

Question 13

Hi-C

Answer 13

mapping DNA 3D structure by using proteins to ‘hold’ DNA together as it is organised in the organism, ends can be sequenced and we can map structure from this info

Question 14

eukaryotic DNA organisation

Answer 14

chromatin blah blah etc
-histone octamer
-147bp wrap around a nucleosome twice
-tails of the monomers extend out, these have opposite charges to the DNA to help mediate interactions

Question 15

acetylation vs methylation

Answer 15

acetylation removes basic charge, weakening interactions w DNA
methylation is more complex- doesn’t directly alter charge, changes histone affinity for various binding proteins, can therefore have both effects on transcription

Question 16

histone H1

Answer 16

interacts with core nucleosome and linker DNA, to stabilise chromatin- important in formation of the 30nm fibre which packs in nucleosomes

Question 17

example of some chromatin condensation states

Answer 17

11nm ‘beads on a string’
700nm whole section of chromosome

Question 18

TAD

Answer 18

topologically associated domain- mapped by stuff like Hi-C

Question 19

chromosome organisation

Answer 19

TAD > component > chromosome territory in the nucleus

Question 20

histone involvement in TAD formation

Answer 20

very cosnerved relationships between the two- ‘clustering; with some modifications, not clear if the histone code promotes the interactions, or the interactions spread the histone codes

Question 21

how are bacterial genes organised to increase efficiency of transcription?

Answer 21

quicker for genes closer to the origin to have 2 copies

Question 22

R number

Answer 22

dna replication time/cell division time- represents how much replication limits rate of cell division

Question 23

how does 3D organisation impact expression in bacteria?

Answer 23

genes closer to the surface of the nucleoid are more easily accessed by RNAP, or those located near RNAP clusters

Question 24

how many RNAP molecules in a cluster

Answer 24

350ish

Question 25

correlation between physical proximity and transcription levels

Answer 25

tend to be related- e.g. physically close genes are transcribed a similar amount, better to separate genes which need separate regulation

Question 26

term for physically close genes

Answer 26

‘gene neighbourhood’

Question 27

why does gene position not affect dosage in eukaryotes?

Answer 27

genes are in equal numbers most of the time, as mitosis is a v small part of the cell cycle

Question 28

how do DNA and polymerase organisation relate in eukaryotes

Answer 28

generally the DNA is pulled to fixed polymerases- so what happens with DNA is more dictated by other things

Question 29

example of eukaryotic gene clusters

Answer 29

primary metabolic clusters in plants- nitrate genes
secondary metabolic clusters- e.g. penicillin production

these clusters facilitate co-inheritance

Question 30

vertebrate gene clusters

Answer 30

hox genes- 4 clusters on 4 chromosomes involved in body type patterning

Question 31

impact recombinatory processes have on gene organisation

Answer 31

genes are more likely to spread near the telomeres- benefit to a gene being here?

Question 32

what is QTLM

Answer 32

quantitative trait locus mapping

Question 33

how does linkage disequilibrium impact QTL mapping?

Answer 33

harder to identify a location if there is higher LD, as the effect carries further away from a specific point

Question 34

how does R influence genome organisation?

Answer 34

in higher R species, some genes are even more likely to be close to the origin- e.g. RNAP genes and rDNA

Question 35

repetitive content vs genome size

Answer 35

proportion of repetitive content increases as genome size increases

Question 36

when can understanding genome organisarion be important?

Answer 36

health- e.g. how genetic variations cause disease, if the mechanism may involve these 3D structure variations
plant breeding- stuff nearer the telomeres impacts selection, so may impact which genes you select for etc
also vice versa- genes near the centromere are harder to pass on, so would then need to get the whole chromosome to be inherited