A rigorous measure of genome-wide genetic shuffling that takes into account crossover positions and Mendel’s second law

Abstract

AbstractComparative studies in evolutionary genetics rely critically on evaluation of the total amount of genetic shuffling that occurs during gamete production. However, such studies have been ham-pered by the fact that there has been no direct measure of this quantity. Existing measures consider crossing over by simply counting the average number of crossovers per meiosis. This is qualitatively inadequate because the positions of crossovers along a chromosome are also critical: a crossover towards the middle of a chromosome causes more shuffling than a crossover towards the tip. More-over, traditional measures fail to consider shuffling from independent assortment of homologous chromosomes (Mendel’s second law). Here, we present a rigorous measure of genome-wide shuffling that does not suffer from these limitations. We define the parameter r̅ as the probability that the alleles at two randomly chosen loci will be shuffled in the production of a gamete. This measure can be decomposed into separate contributions from crossover number and position and from independent assortment. Intrinsic implications of this metric include the fact that r̅ is larger when crossovers are more evenly spaced, which suggests a novel selective advantage of crossover interference. Utilization of r̅ is enabled by powerful emergent methods for determining crossover positions, either cytologically or by DNA sequencing. Application of our analysis to such data from human male and female reveals that: (i) r̅ in humans is close to its maximum possible value of 1/2, (ii) this high level of shuffling is due almost entirely to independent assortment, whose contribution is ~30 times greater than that of crossovers.