genome organisation- 4 lectures Flashcards
key features of bacterial genomes
-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
eukaryotic genome features
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
an average human gene consists of:
○ 4 exons
○ 1000bp CDS
○ 20kbp genomic footprint
○ 95% intron
percentage of the human genome which is transcribed into RNA
5%- 1% of that is mRNA
centromere features
5 million bp, consists of repeats called α-satellites
telomere features
10k bp long, made of short repeats, 1% of the total genome
types of repetitive DNA
satellites- short repeats
retrotransposons- larger regions which move themselves around the genome- LTRs, LINEs, SINEs, these make up around 30% of an average gene
why is studying repetitive DNA useful to us?
repetitive DNA is useful for studying population genetics and conservation
example of an organism with weird genome organisation
trypanosomes- 10k genes, with unusually few promoters- genome made up of transcriptional ‘units’
reliance on splicing, gene regulation happens post-translationally
viral 3D genome organisation
generally not that compact, genes fitting inside a virion
length/diameter ration for virus vs bacteria
100 vs 1500 (bacteria)
bacterial genome features
more organised than viral- in a nucleoid in the middle of the cell, folded up nicely
Hi-C
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
eukaryotic DNA organisation
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
acetylation vs methylation
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
histone H1
interacts with core nucleosome and linker DNA, to stabilise chromatin- important in formation of the 30nm fibre which packs in nucleosomes
example of some chromatin condensation states
11nm ‘beads on a string’
700nm whole section of chromosome
TAD
topologically associated domain- mapped by stuff like Hi-C
chromosome organisation
TAD > component > chromosome territory in the nucleus
histone involvement in TAD formation
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
how are bacterial genes organised to increase efficiency of transcription?
quicker for genes closer to the origin to have 2 copies
R number
dna replication time/cell division time- represents how much replication limits rate of cell division
how does 3D organisation impact expression in bacteria?
genes closer to the surface of the nucleoid are more easily accessed by RNAP, or those located near RNAP clusters
how many RNAP molecules in a cluster
350ish
correlation between physical proximity and transcription levels
tend to be related- e.g. physically close genes are transcribed a similar amount, better to separate genes which need separate regulation
term for physically close genes
‘gene neighbourhood’
why does gene position not affect dosage in eukaryotes?
genes are in equal numbers most of the time, as mitosis is a v small part of the cell cycle
how do DNA and polymerase organisation relate in eukaryotes
generally the DNA is pulled to fixed polymerases- so what happens with DNA is more dictated by other things
example of eukaryotic gene clusters
primary metabolic clusters in plants- nitrate genes
secondary metabolic clusters- e.g. penicillin production
these clusters facilitate co-inheritance
vertebrate gene clusters
hox genes- 4 clusters on 4 chromosomes involved in body type patterning
impact recombinatory processes have on gene organisation
genes are more likely to spread near the telomeres- benefit to a gene being here?
what is QTLM
quantitative trait locus mapping
how does linkage disequilibrium impact QTL mapping?
harder to identify a location if there is higher LD, as the effect carries further away from a specific point
how does R influence genome organisation?
in higher R species, some genes are even more likely to be close to the origin- e.g. RNAP genes and rDNA
repetitive content vs genome size
proportion of repetitive content increases as genome size increases
when can understanding genome organisarion be important?
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
