Workshop recap · What did mutagenesis reveal about ace gene in C. elegans? o Four genes encode acetylcholinesterase (AChE) in C. elegans. o C. elegans is unusual in having four ACE genes. Most animals have only one ACE gene. It was unfortunate the C. elegans was chosen as the model organism to investigate acetylcholinesterase. 0 ACE-1 and ACE-2 are located on chromosome X and I. They have different locations and probably duplicated distantly in evolution. o ACE-1 is expressed in muscle cells and a few neurons, whereas ACE-2 is mainly expressed in motoneurons. These genes have different expression patterns. ACE-1 forms tetramers, whereas as ACE-2 forms dimers. The enzymes encoded by these genes combine in different ways (tetramers v dimers). This changes their biochemistry and may alter how and when they function. o ACE-1 and ACE-2 proteins share 35% identity in amino acids. This level of identity is quite high. About one third of the amino acids are identical in these proteins. The level of similarity is likely higher because some amino acids have similar properties. o Despite this identity ACE-1 and ACE-2 have different pharmacological properties. The differences in amino acids between these proteins determine important differences in their function. o ACE-3 and ACE-4 are in a tandem repeat on chromosome II separated by only ~350 nucleotides. ACE-4 is very similar to ACE-3 (54 % amino acid identity). These are likely to have appeared more recently than ACE-1 and ACE-2 o (the closer duplicate genes are, the more recently they will have evolved) ACE-3 produces only 5% of the total AChE activity and is expressed only in a few cells, ACE-3 associates with the dimers formed by ACE-2, but it able to sustain ace-1; ace-2 double mutants. ACE-3 is resistant to most inhibitors - it also has different pharmacological properties. ACE-4 is transcribed at lower levels than the other ACE genes, but no enzyme activity has been detected in vivo using current methods. Acquisition of new genes by duplication events · homologous genes - genes that share a common evolutionary ancestor · orthologous genes - homologous genes located in the genomes of different organisms · paralogous genes - two or more homologous genes located in the same genome · pseudogene - an inactivated & non-functional copy of a gene · We can be more precise about gene duplication: o subfunctionalisation - the duplicated genes perform different aspects of the original gene's function o neofunctionalisation - one of the duplicated genes acquires a new function
Gene duplication Selective pressure on both genes Selective pressure on just one of the genes 1 Genes stay similar One copy degrades Genomes 3 p 570 One copy acquires a new function Gene duplication in the context of genome evolution . The olfactory receptor gene family represents about 3% of our total no. of genes (the largest gene family) o Richard Axel and Linda Buck identified a large family of genes for odour receptors in 1991 (and were awarded a Nobel prize) o Each odour