Download Gen660_Week4a_HGT_2014

De novo creation of new genes
1.
Retrotransposition (+/- cooption of other sequences)
Often see short flanking repeats due to mechanism of TE integration
Integration into the genome (in NUCLEUS)
Reverse transcription by TE polymerases
(in CYTOSOL)
AAAAA
Splicing to remove intron
AAAAA
Pre-mRNA
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De novo creation of new genes
1.
Retrotransposition (+/- cooption of other sequences)
Often see short flanking repeats due to mechanism of TE integration
Integration into the genome (in NUCLEUS)
Reverse transcription by TE polymerases
(in CYTOSOL)
AAAAA
Splicing to remove intron
AAAAA
Pre-mRNA
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De novo creation of new genes
1.
Retrotransposition (+/- cooption of other sequences)
2.
Gene duplication into other sequences = chimeric structure/regulation
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De novo creation of new genes
1.
Retrotransposition (+/- cooption of other sequences)
2.
Gene duplication into other sequences = chimeric structure/regulation
3.
Cooption of non-coding DNA (from introns, intergenic sequence)
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De novo creation of new genes
1.
Retrotransposition (+/- cooption of other sequences)
2.
Gene duplication into other sequences = chimeric structure/regulation
3.
Cooption of non-coding DNA (from introns, intergenic sequence)
4.
Horizontal gene transfer (very prevalent in bacteria)
- also observed from bacterial parasites to insect hosts
Challenge in distinguishing Novel Gene vs. missed orthology due to rapid evolution
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Horizontal (or Lateral) Gene Transfer
Horizontal Transfer
Vertical Transfer
(e.g. along species tree)
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Mechanisms of HGT
Steps 1-3: DNA Transfer
Step 4: Persistence (replication) in Recipient
Step 5: Selection to maintain sequence
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From Thomas & Nielsen. Nat Rev Microbiol. 2005
Mechanisms of HGT:
DNA Transfer
A. Transformation: direct uptake of naked DNA
• Donor and recipient do NOT need to co-exist in the same time/space
• Can occur across distantly related species
• Efficiency depends on ‘competency’ of recipient
Some species readily take up DNA
Other species have transient (e.g. stress/starvation) competency
B. Transduction via bacteriophages
• Phage can package random or adjacent donor DNA
• DNA size limited by capsid packaging (but still can be 100 kb)
• Recipient must be able to take up phage (through specific receptors, etc)
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Mechanisms of HGT:
DNA Transfer
C. Conjugation: direct connection between two bacteria
•
•
•
Species need to co-exist in the same environment
Need pairs of species that can conjugate
DNA transferred as mobile element or plasmid
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Mobile (Transposable) Elements
& Bacteriophages are a
major force of HGT
Transposase
Antibiotic resistance genes
IR
(inverted repeat)
IR
(inverted repeat)
Some mobile elements excise and reintegrate,
others are replicative.
Some integrate at specific sites (“att” sites) & often
adjacent to tRNAs.
Many can excise or replicate neighboring DNA
Many triggered to move upon environmental stress
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Mechanisms of HGT:
DNA Stabilization
Transferred DNA needs to replicate & get passed on
•
•
•
•
Episomal replication (e.g. plasmid)
Integration along with phage genome or mobile element
Homologous recombination
Non-homologous (“illegitimate”) recombination
Benefit of transferred DNA needs to outweigh its cost
•
•
Burden of extra DNA and/or protein synthesis
Famous cases of HGT involve antibiotic resistance or pathogenicity
New DNA needs to be expressed to provide beneficial functions
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Question: How does the prevalence of operons in bacteria
influence evolution by Horizontal Gene Transfer?
Having suites of functionally related genes linked and co-expressed
= easy to transfer whole pathways
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Genomic Islands: families of horizontally transferred genes
Often near tRNA
Often contain own mobility genes
& sequences
Evolve through gene acquisition & loss
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From Juhas et al. 2009. FEMS Micro
Grey = sequence homology around 4 genomic islands (2 related to pathogenicity
and 2 related to environmental responses); black = Genomic Islands
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From Juhas et al. 2009. FEMS Micro
Detecting HGT sequences
1. Often have unusual sequence characteristics (GC content, codon usage,
di-nt frequencies) compared to the rest of the genome
Signatures of other genomes speckled in the host.
2. Often flanked by repeat elements (from phage or mobile element insertion)
or tRNAs (since integration often near tRNAs)
3. Gene tree is very different from the species tree
1. These days, easily detected by sequencing many isolates of the same ‘species’
and detecting variable gene sequences
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From Tenaillon et al. Nat Revs Micro 2010
Effects of HGT on Gene Trees
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From Keeling & Palmer Nat Rev Genetics 2008
Best evidence for HGT: sequencing of many strains of the same ‘species’
… but What is a bacterial species?? No sex, lots of HGT across species …
the idea of the Pan Genome: the total gene pool represented within a ‘species’
Core Genome: genes common to ALL isolates of a given species
Accessory Genome: variable parts found in subsets of isolates
Bacterial Pan Genomes
In study of 8 E. coli genomes:
Only 40% of the Pan Genome was made
up of the Core Genes
But extrapolation suggests many more accessory
genes in E. coli (but not all species … why?)
From Mira et al. 2010. Internat. Micro
Bacterial Pan Genomes
In study of 8 E. coli genomes:
Only 40% of the Pan Genome was made
up of the Core Genes
But extrapolation suggests many more accessory
genes in E. coli (but not all species … why?)
Mobile elements more prominent for some
species
Some species more readily take up DNA;
others do not do homologous
recombination well
Some species occupy very narrow niche –
little exposure to other DNA, etc
From Mira et al. 2010. Internat. Micro
Different genes enriched in the Core vs. Accessory Genomes
Core Genomes: ‘Housekeeping’ functions
Accessory Genomes:
* Environmental genes
* Poorly characterized genes
* Orphan genes (no homology to any known gene)
* More mobile elements, phage sequences, repeats
Orphan genes:
Considerably shorter than normal genes
Some are fragments of other genes
Some may be non-functional
May original from poorly sampled world of phage genes
Metagenomics: uncovering the world of new bacterial/phage genes
Metagenomics: sequencing the entire pool of DNA found in environmental sample
* Done without cloning or culturing (most bacteria cannot be cultured!)
* Computational methods of linking sequence back to particular species
* Work to try to assemble genomes
* Most analysis to date done on pools of sequences, not
genomes assembled from those sequences
Ed DeLong: 3:30 pm Thursday, February 12: Microbial Sciences Seminar Series
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