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)

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

Fig. 6.11

GLOBIN GENE EVOLUTION

Lodish Fig. 3.11

Evolution of – globin gene cluster in mammals

Hoffmann Mol Biol Evol 25:591, 2008

Unprocessed globin pseudogenes

What features might a “processed” globin pseudogene have?

Fig. 6.12

Globin superfamily - estimating time of gene duplication events

Fig. 6.9

- 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

- 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

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

Order of duplication events?Fig. 6.5

Fig. 6.6

Trypsinogen gene Antifreeze gene in Antarctic cod

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

.... 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

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

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

Fig. 6.21

Some possible types of alternative splicing

Example of sex determination pathway in Drosophila

see Fig. 6.22

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

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

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

A protein C protein

K protein

Fig. 6.20

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”

Wistow TIBS 1993

Recruitment of various eye lens crystallins during vertebrate evolution

= lactate dehydrogenase

= enolase

= NADPH-dependent reductase

Differences in eye lens proteins between octopus & squid

Tomarev J Biol Chem 266:24266, 1991

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