Role of premeiotic replication in gene conversion

Abstract

CURRENT molecular models of meiotic recombination have attempted to explain both classical reciprocal recombination (crossing over) and non-reciprocal intragenic recombination (gene conversion), with a single unified mechanism^1,2. An important assumption inherent in such models is that both types of recombination occur during the prophase following premeiotic chromosome replication. To date, however, only crossing over (chiasma) has been convincingly shown to occur during meiotic prophase³. Gene conversion, which has been most extensively studied in the ascomycete fungi⁴, has, for a number of cogent reasons⁵, also been assumed to occur during prophase, yet direct evidence supporting this critical point is lacking. In fact, in an important paper⁶, concerning recombination in yeast, evidence was presented indicating that intragenic recombination and premeiotic replication coincided, a finding which argues against much current speculation. To clarify this situation we simultaneously measured premeiotic replication and gene conversion in the yeast Saccharomyces cerevisiae, and examined the genetic consequences of inhibiting DNA synthesis with hydroxyurea (HU). We show that during the premeiotic S phase cells acquire a ‘potential’ for completing gene conversion, but that the actual formation of stable intragenic recombinants occurs after replication and depends on a period of postreplicative DNA synthesis.