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

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

Acquisition of new genes

Gene duplication

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

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

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

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

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

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

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

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

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

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

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

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

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.

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

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) 292-298. Hurles, M. (2004) Gene duplication: the genomic trade in spare parts. PloS Biology 2(7): 0900-0904