Recursive Ectopic Gene Conversion Leads to Elevated DNA Mutation, Gene Loss, and Novel Gene Formation in Aspergillus

Gene conversion contributes to gene copy number changes, DNA mutations, and functional innovation and has been widely reported in three domains of life. However, it has hardly been described in Aspergillus, including industrially and commercially important or pathogenic fungi. Here, we revealed multiple sets of homologous genes located in a region of chromosome 1 of A. flavus, and its orthologous counterpart of A. oryzae. Phylogenetic analysis showed evidence of frequent gene (DNA) conversion between ectopic paralogs in each species, accompanied by prominent point mutations and DNA deletion (from several to hundreds of base pairs). At least two independent cases showed that the converted genes in A. oryzae have been repeatedly split into shorter genes by the introduction of stop codons, and then ectopic conversion rendered paralogous genes (regions) to have the same configuration of tandemly located new genes. Inference of nucleotide substitution and ancestral gene content showed that the conversion-affected regions have seen 3.48 times as many substitutions and 4-6 times as many gene losses compared to the non-affected regions. We predicted that a DNA loop between proximal regions, in the common ancestor and inherited by each species, facilitates ectopic gene (DNA) conversion and elevated rates of mutations and losses. Overall, we found that gene conversion proves to be a key factor resulting in genome instability, elevated gene evolutionary rates, and an effective avenue to produce new genes, likely leading to the speciation of two Aspergillus lineages.