Deep Genome-Wide Measurement of Meiotic Gene Conversion Using Tetrad Analysis in Arabidopsis thaliana
Gene conversion, the non-reciprocal exchange of genetic information, is one of the potential products of meiotic recombination. It can shape genome structure by acting on repetitive DNA elements, influence allele frequencies at the population level, and is known to be implicated in human disease. But gene conversion is hard to detect directly except in organisms, like fungi, that group their gametes following meiosis. We have developed a novel visual assay that enables us to detect gene conversion events directly in the gametes of the flowering plant Arabidopsis thaliana. Using this assay we measured gene conversion events across the genome of more than one million meioses and determined that the genome-wide average frequency is 3.5×10−4 conversions per locus per meiosis. We also detected significant locus-to-locus variation in conversion frequency but no intra-locus variation. Significantly, we found one locus on the short arm of chromosome 4 that experienced 3-fold to 6-fold more gene conversions than the other loci tested. Finally, we demonstrated that we could modulate conversion frequency by varying experimental conditions. During the production of gametes, most sexually reproducing organisms undergo meiotic recombination. The most familiar form of meiotic recombination is crossing-over, which results in the reciprocal exchange of DNA between parental chromosomes and is important for chromosome segregation as well as generating new allelic combinations in progeny. The same molecular mechanisms that facilitate crossing-over can also enable the non-reciprocal exchange of genetic information between chromosomes in the process called gene conversion. Understanding gene conversion is important because it influences allele frequencies and has been implicated in human diseases. Unfortunately, it has been difficult until now to measure directly except in organisms, like fungi, that group their gametes after meiosis. In this study we have developed a novel assay system that enables us to measure gene conversion directly in the model multi-cellular eukaryote A. thaliana (a flowering plant). Using this assay system we measured gene conversion frequencies across the Arabidopsis genome in more than 1 million meioses and also demonstrated that we can manipulate those frequencies by varying experimental conditions.