Methods and compositions are provided for the efficient in vivo
diversification of gene-products in filamentous fungi, starting from (but
not limited to) two or more copies of a single gene constituent. The
diversification involve use of the Repeat-Induced Point mutation (RIP)
process in N. crassa, and other fungi that have analogous mutational
processes. The invention takes advantage of the induction of G:C to A:T
transition mutations specific to duplicated DNA sequences during the
premeiotic dikaryon phase of the life cycle of the fungus. The methods
and compositions of the invention can be utilized to generate diversity
in target genes, and are proposed for the purpose of altering and
generating novel forms and activities of gene-products thus encoded.
Duplicated genes may be introduced into the organism and are present
either in tandem, or at separate ectopic locations within the genome of
the fungus. After crossing the resulting transformant(s), sexual progeny
can then be selected which contain the mutated gene, and subsequently
screened for a desired product.