1. Evolution of eukaryotic genomes
Lecture 7: Acquisition of new genes I- Gene duplication

2. Acquisition of new genes
Fruitfly
Nematode
Ciona intestinalis
Yeast
Human
Chicken
Haemophilus influenzae
E. coli
# of genes
1790
5380
6000
19,700
13,770
10,990
17,710
22,200
(Sea squirt)
Prokaryotes
Eukaryotes

3. Acquisition of new genes

4. Gene duplication

5. Duplications occur at all genomic scales!
Short indels
Apparent Frequency
Domain (exon)
Gene
Gene cluster
Segment
Chromosome
Genome

6. Evidence for importance of gene duplication
Gene families (paralogous genes)
Genes which share a common ancestor as a result of gene duplication
May be clustered together or dispered through the genome with diverse function

7. Mechanisms of gene duplication
Unequal CO  tandem duplication
Between homologous chromosomes
Duplication of a segment of DNA in one of the replication
Unequal sister chromatid exchange
Same but between chromatids
Retrotransposition (L9 and 10)
Chromosomal duplication (L5)
Replication slippage
Very short sequences
Eg. microsatellites

8. Fates of duplicated genes
Blue box = gene
Arrows = tissue specific promoters

9. Fate of duplicate genes
30-60% of eukaryotic genes are found in duplicate
May have degenerate mutations
Pseudogenes
Non-functional genes
Why keep duplicate genes??
neofunctionalization
Duplicate gene acquires a new function
Subfunctionalization
an ancestral function is divided between duplicate genes
Usually a change in regulatory element affecting expression

10. Pseudogenization Process whereby functional genes become a pseudogene
Occurs in the first million years after duplication if the gene is not under selection
Gene duplication generates function redundancy
Not usually advantageous to keep identical copies of the same gene
Mutations disrupting structure and function and not deleterious
Accumulate until gene becomes non-functional pseudogene
Usual time frame is 4 my

11. Conservation of gene function
Paralogous
two genes (or gene clusters) in the same organism which show structural similarity indicating they once derived from a common ancestral gene but have since diverged
Orthologous
Duplicated genes in two different species (may or may not have the same function)
Concerted evolution
A mode of gene family evolution in which members of a family remain similar in sequence and function because of frequent gene conversion and/or unequal CO
Gene conversion
a recombination process that non- reciprocally homogenizes gene sequences
Purifying selection
Natural selection that prevents the fixation of deleterious alleles

12. Concerted evolution Gene conversion homogenizes paralogues
Duplicates can be highly similar between species but divergent between species (orthologues)

13. Conservation of gene function
Presence of duplicate genes may be beneficial since more protein is provided
Eg. Histones and rRNA genes
Paralogous genes retain the same function by gene conversion (concerted evolution)
Purifying selection against mutations which modify gene function may allow this preservation

14. Subfunctionalisation
Two genes with identical functions unlikely to be maintained in the genome
Each daughter gene adopts part of the function of their parental gene
Changes often occur in expression pattern of the two genes

15. Subfunctionalisation
Squares = genes
Ovals = transcription regulators
A2 (t1) and A1(T2) lose function
Both genes still neccessary
Not clear what percentage of genes evolved by subfunctionalisation

16. Subfuncationalisation
Duplication-degeneration-complementation model (DDC)
Degenerative changes occur in both regulatory sequences
Expression is complementary
Reconstitutes the expression pattern of the original gene

17. Neofunctionalisation
Most important outcome of gene duplication
Are some example of completely unrelated function arising from duplicate genes – but uncommon
Usually, a related function evolves after gene duplication
Eg. Red green sensitive opsin genes in humans
Humans can distinguish three different wavelengths
Mice only two
caused by TWO substitutions.

18. Contribution of gene duplication to genomic evolution
Production of new genetic material for
Genetic drift
Mutation
selection
Genomes as we know them today (eg. Immunoglobulin genes) would be impossible with gene duplication
Species specific gene duplication
Species specific gene function
Contributes to species divergence

19. Refereneces
Brown, T.A. (2002) How genomes replicate and evolve. In Genomes2. BIOS Scientific publishers: Oxford.
Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. (2002) Cells in their social context: In Molecular biology of the cell. Garland Science: NewYork.
Presgraves, D.C. (2004) Evolutionary genomics: new genes for new jobs. Current Biology. 15(2).
Zhang, J. (2003) Evolution by gene duplication: an update. Trends in ecology and evolution. 18(6)
Hurles, M. (2004) Gene duplication: the genomic trade in spare parts. PloS Biology 2(7):