evolution of new genes how do complex organisms acquire extra genes (for new functions)? … and...
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EVOLUTION OF NEW GENES
How do complex organisms acquire extra genes (for new functions)?
… and extra forms of regulation?
1. Gene duplication
- one copy can perform original function and second one mayevolve new function
Tandem arrays
Dispersed copies
Multi-gene families – sets of genes derived by duplication of ancestral gene
Pseudogene – non-functional member of gene family
chr 1
chr 5
(or degenerate into pseudogene)
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Homologous genes
- share common evolutionary origin
Orthologous genes
- descendants of an ancestral gene that was presentin the last common ancestor of two or more species
Paralogous genes
- arose by gene duplication within a lineage
ancestor
Species 1
Species 2
Species 3
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Fig. 6.11
GLOBIN GENE EVOLUTION
Lodish Fig. 3.11
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Evolution of – globin gene cluster in mammals
Hoffmann Mol Biol Evol 25:591, 2008
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Unprocessed globin pseudogenes
What features might a “processed” globin pseudogene have?
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Fig. 6.12
Globin superfamily - estimating time of gene duplication events
Fig. 6.9
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- calculate rates of nt sub (r and r for genes and in species 1 and 2
r = k / 2TS r = k / 2TS
- assume TS is known from geological record
- score number of nt sub per site for each gene (that is, and ) in the 2 species to determine k and k
- average rate r = (r + r) / 2
- then to estimate TD (where TD = k / 2 r) , need to know k , the number ofsub per site between genes and
To determine TD
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- to determine average k , carry out 4 pairwise comparisons
1. Gene from species 1 and gene from species 2
2. Gene from specieis 2 and gene from species 1
3. Both genes from species 1
4. Both genes from species 2
- depending on degree of divergence may choose to use only synonymous or only non-synonmyous sites…
- if rate constancy holds, the 4 pairwise comparisons should beapproximately equal
TD = k / 2 r
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2. Internal domain duplication
- repeated sequence may correspond to functional or structuraldomain within protein
- eg. ovomucoid gene in chickens
- enzyme which inhibits trypsin and has 3 domains (as a result ofduplication events), each of which can bind one molecule of trypsin
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Order of duplication events?Fig. 6.5
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Fig. 6.6
Trypsinogen gene Antifreeze gene in Antarctic cod
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3. Exon (or domain) shuffling
- exon duplication & incorporation into another gene
- functional or structural modules form mosaic proteins
- may be mediated by intron recombination
Gene 1: 1 2 3 4
Duplication of exon 3& flanking region
3 exon a exon b
Gene 2:3
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.... CCG|GAA| ACG|GGT| ....
1 2 3 1 2 3
GT AG
.... CCG|G AA|ACG|GGT| ....
1 2 3
GT AG
.... CCG|GA A|ACG|GGT| ....
1 2 3
GT AG
Phase limitations on exon shuffling:
If intron lies between 2 codons = “phase 0”
If intron between 1st and 2nd nt of codon = “phase 1”
If intron between 2nd and 3rd nt of codon = “phase 2”
see Fig. 6.17
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Do exons correspond to functional (or structural) domains at protein level?
In some cases, yes
F1 = fibronectin module
KR = kringle domain
EG = EGF finger moduleFig. 6.14
Stryer Fig. 10.35
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EVOLUTION OF NEW FUNCTION (without duplication)
1. Alternative splicing pathways
- single gene can give rise to different mRNAs (and different proteins)
pre-mRNA
mRNA 1 mRNA 2
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Fig. 6.21
Some possible types of alternative splicing
Example of sex determination pathway in Drosophila
see Fig. 6.22
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eg. mitochondrial-type rps14 gene located within intron of sdh2 gene
sdh2 ex1 sdh2 ex2rps14
Figueroa BBRC 271: 380, 2000
Example of “hitch-hiking” through alternative splicing
- organellar genes which move to nucleus during evolution, canonly be functional if properly expressed
- protein imported back into mitochondria (and N-terminal extension removed)
- transferred rps14 gene exploits transcription/translation signals & protein targeting (N-terminal) signals of host sdh2 gene
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2. RNA editing
- modification of RNA so that message is changed
eg. certain C’s in pre-mRNA changed to U’s
Lodish Fig. 12-57
eg. apolipoprotein B in mammals
In liver: lipid transport in circulation, LDL receptor binding domain
In intestine: truncated protein, role in dietary lipid absorption
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Fig. 6.20
3. Overlapping genes
- DNA region codes for more than one protein
- different reading frames or complementary strand used
- in viruses, bacteriophages… (compact genomes)
- rate of evolution expected to be slower for such regions
Bacterophage X174 genome
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A protein C protein
K protein
Fig. 6.20
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4. Gene sharing
- gene acquires new function without duplication or lossof original function
- eg. eye lens crystallin (usually mixture of various structural proteins)
- in different animals, different proteins have been recruited
(eg. LDH, enolase, heat shock proteins…)
in response to changing visual environments
aquatic – optically dense, high refractive index
terrestrial – lens softer, low RI, focus at distance
nocturnal vs. diurnal verebrates…
“molecular opportunism”
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Wistow TIBS 1993
Recruitment of various eye lens crystallins during vertebrate evolution
= lactate dehydrogenase
= enolase
= NADPH-dependent reductase
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Differences in eye lens proteins between octopus & squid
Tomarev J Biol Chem 266:24266, 1991
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Steps in eye lens gene recruitment
1. Change in regulation so that “housekeeping” gene “up-expressed” in lens
multi-functional protein
2. Subsequent aa changes may be favourable for one role,but not other
adaptive conflict
3. Resolved by duplication event or reversion back to originalfunction only
… and a different gene then recruited for eye lens protein