10. Introns Flashcards
What are introns?
Introns - non-coding regions interspersed between exons in eukaryotic genoems
Need to be cut out in splicing by spliceosome - a complex 300 protein + 5 RNA subunit machinery
GT-AG intron/exon boundary
What are the types of introns?
Introns:
- spliceosomal introns - splcied out by spliceosome - in eukaryote nuclear / viral genomes
- group I introns - self-splicing - bacteria, organelles, within rRNA genes
- group II introns- self-splicing - bacteria, organelles
Does the number of introns increase linearly with number of exons?
No, the larger the genome - the more coding regions BUT not linear intron DNA increase - a spike in intron proportion in animals - alternative splicing in more complex organisms
What are the costs of introns in genomes?
Intron costs - metabolic costs:
- pointless transcription of extra DNA -> mRNA
- spliceosome is a complex machinery of 300 proteins and 5 RNAs
- 1/3 of human genetic diseases caused by defective splice-sites
BUT
- highly expressed genes in humans have shorter introns
- rapidly regulated genes have fewer introns
- flying vertebrates have shorter introns - because need fast metabolism - introns slow don metabolism
What are the benefits of introns?
Hypotheses for intron benefits to eukaryotes:
- alternative splicing - can create more proteins from the same gene - several isoforms
- Exon shuffling - recombining differen exons can help create new genes - better adaptation
- more recombination - longer genes have better chances of recombination - unlikely explanation of intron benefit
Explain alternative splicing
Alternative splicing - the possible mechanisms:
- exon skipping
- exon swapping
- alternative splice sites
Explain exon skipping as a mechanisms of alternative splicing
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Explain exon swapping as a mechanisms of alternative splicing
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Explain alternative splice sites as a mechanisms of alternative splicing
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How is exon joinign decided in alternative splicing?
Different protein isoforms of the gene have specific exon orders - combinations decided by the spliceosome
Explain exon shuffling as a benefit of introns in genomes
Exon shuffling allows generation of new genes by combining different exons
What is a studied example of exon shuffling?
Serine proteases - involved in blood coagulation - different factors involved but have similar secondary protein structures
What is the evidence that serine proteases have undergone exon shuffling?
Structural + genomic analysis:
serine proteases have undergone exon shuffling in protein generation: have similar domain structures but in different orders - came from duplication of exons + shuffling to other genes -> different proteins
Explain what are intron phases
Intron phases - how introns are spliced out:
- phase 0 - between codons
- phase 1 - breaks codon after 1 base
- phase 2 - breaks codon after 2 bases
- phase 0 - breaks codon after 3 bases - same as between codons
How does exon shuffling involve intron phases?
For exon shuffling exons must be spliced in identical phases to be joined together
What is the hypothesis when and why introns emerged
Now introns useful for alternative splicing and exon shuffling BUT natural selection cannot anticipate the future - what introns will develop into:
first protein coding genes short - longer genes evolved by joining - introns trapped between the joined exons - predictions:
- exons encode functional domains
- intron loss generated longer exons
- evidence for ancient introns
How was the prediction that exons and not introns encode functional domains tested?
Structural protein analysis - introns found at turns - in between functional units => functional parts in exons
How was the prediction that intron loss generated longer exons tested?
Intron loss possibly explained by retrotransposition of reverese transcribed mRNA back into genome
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How was the evidence for ancient introns proposed?
Unlikely that all introns were lost in earlier species - probably evolved late in eukaryotic evolution
Supposing introns evolved late, what events must have also evolved for introns to function like they currently do in eukaryotes?
- insertion of parasitic and self-splicing element (like group I / II introns) - acquired in mt endosymbiosis
- evolution of spliceosome
- accummulation of introns
- exploitation of alternative splicing and exon shuffling
Lecture summary
What are the applications of genomics data?
