ACTIVATION INDUCED DEAMINASE (AID)

1 . A cell comprising a nucleic acid encoding an Activation Induced Deaminase (AID) polypeptide, or an AID variant, derivative or homologue, and having a mutator phenotype.

2 . The cell of claim 1 , wherein said cell is a prokaryotic cell.

3 . The cell of claim 1 , wherein said cell is an eukaryotic cell.

4 . The cell of claim 1 , wherein the AID homologue is Apo1bec-1, Apobec-1, Apobec3C or Apobec3G.

5 . A fusion protein comprising an AID polypeptide, or AID variant, derivative or homologue thereof, having a mutator phenotype operably linked to one half of a specific binding pair.

6 . The fusion protein of claim 5 , wherein said one half of a specific binding pair is a DNA binding domain.

7 . A vector comprising a nucleic acid encoding the fusion protein of claim 5 .

8 . A cell comprising a nucleic acid encoding the fusion protein of claim 5 .

9 . A method for preparing a gene product having a desired activity, comprising the steps of:

a) expressing a nucleic acid encoding the gene product in a population of cells according to claim 1 ;

b) identifying a cell or cells within the population of cells which expresses a mutant gene product having the desired activity; and

c) establishing one or more clonal populations of cells from the cell or cells identified in step (b), and selecting from said clonal populations a cell or cells which expresses a gene product having an improved desired activity.

10 . A method as claimed in claim 9 , wherein the nucleic acid encoding the gene product is operably linked to the second half of a specific binding pair.

11 . A method of directing mutation to a specific gene product of interest comprising:

i) generating a nucleic acid construct comprising a nucleic acid sequence encoding a specific gene product operably linked to a DNA binding protein recognition sequence;

ii) transfecting said nucleic acid construct into a population of host cells expressing the fusion protein of claim 6 ;

ii) incubating said transfected host cells under conditions suitable for allowing the specific binding pairing of DNA binding protein to DNA binding protein recognition sequence to occur;

iv) identifying a cell or cells within the population of cells which expresses a mutant gene product having the desired activity; and

v) establishing one or more clonal populations of cells from the cell or cells

identified in (iv), and selecting from said clonal populations a cell or cells which expresses a gene product having an improved desired activity.

12 . A method of identifying components of AID-dependent mutation activity comprising expressing AID in a cell deficient in expression or activity of a known gene and assessing mutator activity compared to activity in a cell expressing said gene.

13 . A method of screening for a modulator of AID activity comprising:

(a) expressing AID in a prokaryotic cell;

(b) maintaining the AID-expressing prokaryotic cell in the presence of a selectable medium;

(c) detecting the presence of colonies in the absence or presence of a test compound, wherein a modified number of colonies when compared to a sample in the absence of a test compound is indicative of the ability of the test compound to modify AID mutator activity.

14 . A method of inducing a mutation in a cell comprising administering an AID polypeptide or functional homologue thereof.

15 . A method for treating a disorder characterized by an increased mutation rate, comprising administering an agent that modifies AID functional activity or gene expression.

16 . A method of decreasing hypermutation/resistance to a compound such as an antibiotic in a population of bacteria comprising modulating activity of a bacterial AID homologue.

17 . A construct for use in the method of claim 11 , said construct comprising a coding sequence for the gene product of interest, wherein said coding sequence is placed under the control of a first promoter upstream of the coding sequence and further comprising a second promoter downstream of the coding sequence, wherein said first and second promoters are arranged in opposing orientation so as to allow convergent transcription of the coding sequence.