Gene duplication & Exon shuffling Flashcards
1
Q
How can a genome acquire a new gene?
A
- Horizontal gene transfer
- Exon shuffling
- Duplication and divergence
o 1% chance for 1 gene to duplicate in 1 million years
2
Q
Function of genes
A
- Promiscuous = Side reaction has no biological function
- Bifunctional = both activities have a biological function
- Over evolution, 2 functions diverge → enzymes pick up different mutations → specialise → become better at catalysing one reaction or what was originally a side reaction
3
Q
How is DNA duplicated by recombination?
A
- Unequal crossing over (meiosis)
o Only requires certain lengths of similar sequences
o Can get recombination between sets of repeats that are inappropriately lined up
o One chromosome has duplication; other has deletion → have different daughter gametes → if have selective advantage will survive through evolution - Unequal sister chromatid exchange (mitosis)
o Involves exchange between two chromatids
o Paired up on repeat sequence → one chromatid duplication, one deletion
o Depending on species will not be passed on to progeny - DNA amplification during replication
o In haploid organisms (e.g. bacteria)
o Unequal recombination during replication → ‘replication bubble’: DNA splits up in replication forks → homologous DNA but inappropriate lining up so one strand has duplication of region, other gets deletion - Replication Slippage
o For short DNA sequences e.g. microsatellites, CAG triplet, poly-Q Huntington’s disease
o Not common for genes
o DNA loops out one repeat and starts to re-pair-up downstream → added DNA repeat as part of replication cycle
o Other end has looped out → priming in wrong place → deleting the sequence
o Can get insertions or deletions
o Partial duplication of genetic material that codes for protein - Retrotransposition
o Retrotransposons can reverse transcribe RNA copies back into DNA and spread across genomes over evolutionary time
4
Q
Successful gene duplication
A
- Successful = gene survives
- Successful outcome #1 → gene originally w/one copy duplicated → hypothesis: 2 copies should double synthesis rate if everything else is equal
o If beneficial → retain that
o If second copy does not provide dosing advantage → can pick up random mutations → will eventually inactive random mutation → over evolutionary time accumulate mutations → get pseudogenes (no longer fully functional gene) - Successful outcome #2 → getting new function
o “neofunctionalization” or sub-function of parental copies - If selection pressure just for dosage → genes stay similar
- If no selection pressure for second copy → one copy either degrades entirely (pseudogene) or gets a new function if it provides advantage
5
Q
Gene neofunctionalization example
A
- Trypsin vs chymotrypsin
o Evolved to be different proteases
o Trypsin → cuts at Arg & Lys
o Chymotrypsin → cuts at Phe, Trp & Tyr
o Not structurally identical but similarities in proportion of strand/helices and nature of active site
6
Q
Pseudogenes
A
- Copies of functional genes → altered/missing regions
- Often have stop codons/frameshifts/missense mutations → kill reading frame of protein
- May have regulatory role → often producing RNA
- Increase genome size (cost/benefit)
7
Q
Types of pseudogenes
A
- “non-processed” pseudogenes:
o Tandem duplication of genomic region
o Inactivating mutations/incomplete duplications
o Part of genome missing regulatory regions → no promoter, enhancers in correct place but does have original intron/exon structure - “processed” pseudogenes:
o Undergoes reverse transcriptase activity (LINE, retrovirus) → mRNA to cDNA → genome integration to make second duplicated gene copy
o Lacks regulatory regions e.g. introns
o Can have different combinations of exons
o Loses most of promoter region except 5’ untranslated region at front of gene
o Could contain poly(A) tail
o Can integrate into same or different chromosome
8
Q
Examples of pseudogenes
A
- Ribosomal proteins
o Highly duplicated across different species and highly conserved (essential for protein synthesis machinery)
o Associated w/ L1 retrotransposon
o May have functional role as have high expression rate - Humans have 20,000 pseudogenes → most are ribosomal
o 2/3 of these also in chimpanzee genome
o Less than 12 shared w/mouse genome
o Not clear what these genes are doing
9
Q
Multigene families
A
- If duplication is beneficial, multigene family can be formed.
- E.g. rRNA (v. important so highly conserved)
- Tandem gene families = clustered on same chromosome
- Dispersed gene families = on different chromosome
10
Q
Globin superfamily
A
Example of duplication & divergence
Carry out different functions in different tissues
Mixture of co-localised gene sin clusters and dispersal of these across the whole genome on different chromosomes → tandem & dispersed
Can trace evolution over different organisms → compare genes within/between species
Globins are v. common → present in all 3 domains of life
Haem-containing protein domain → v. diverse
Used for oxygen transport, storage, sensing & detoxification
Haemoglobin: tetramer (2α, 2ß)
Myoglobin: monomer
Different structures because changes the property of which they can load/take off oxygen
Others include: neuroglobin, androglobin, cytoglobin, globin E, globin X, globin Y
11
Q
Haemoglobin
A
- Cooperativity in binding:
o Difficulty when oxygen initially tries to bind haem at low concentration
o Each subsequent oxygen binding cooperatively helps the next one within tetramer → get non-linearity in binding curve → sigmoidal curve as haem requires high levels of oxygen to bind oxygen
12
Q
Myoglobin
A
- Found in muscles
- Has simpler binding curve → no cooperativity
- Higher affinity for oxygen
- Having different proteins for oxygen storage and transport w/different binding affinities is useful
13
Q
Genome duplication
A
- Larger duplication than genes/segments is possible → can affect genome structure
- Whole chromosome duplication → trisomy 21 → ‘down syndrome’
o Gene product imbalance
o Reduced life expectancy - Genome sequencing suggested major metazoan lineages have undergone whole genome duplications (WGD)
14
Q
Polyploidy
A
- Multiple complete sets of chromosomes
- Useful in agriculture to make bigger cells → bigger fruit
- ~80% of flowering plants: oats, cotton, potatoes, bananas, coffee, etc
- Common in invertebrates, fish & amphibians; rare in mammals
15
Q
Autopolyploid
A
- Multiplication of identical species within single species
- Meiosis error within single species
- Fertilization of unreduced gametes
- Accidental production of diploid gametes not v. rare (1-40%)
- Can induce disease symptoms:
o ‘Genomic shock’ → widespread activation of transposons, gene expression, recombination (short-term effect)
o These can then stabilise over time → produce fertile gametes and pass down duplications - Need to have even/paired up number of chromosomes to align properly during metaphase
- Autopolyploids can reproduce successfully but cannot breed with parent species → introduces speciation
