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

Abstract

Comparative studies in evolutionary genetics rely critically on evaluation of the total amount of genetic shuffling that occurs during gamete production. Such studies have been hampered by the absence of a 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 toward the middle of a chromosome causes more shuffling than a crossover toward the tip. Moreover, 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 r¯ as the probability that the alleles at two randomly chosen loci are shuffled during gamete production. 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 r¯ is larger when crossovers are more evenly spaced, which suggests a selective advantage of crossover interference. Utilization of r¯ 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) r¯ in humans is close to its maximum possible value of 1/2 and that (ii) this high level of shuffling is due almost entirely to independent assortment, the contribution of which is ∼30 times greater than that of crossovers.

Interplay between Pds5 and Rec8 in regulating chromosome axis length and crossover frequency

“…Most DSBs develop into non-COs, which results in the unidirectional transfer of genetic information from the intact homolog to the broken one ( 1 ). COs promote the reshuffling of genetic diversity, which is helpful for evolutionary adaptation ( 3 – 5 ). COs also work with sister chromatid cohesion to establish physical connections between homologs, allowing proper segregation ( 1 , 2 ).…”

Whole-chromosome fusions in the karyotype evolution ofSceloporus(Iguania, Reptilia) are more intense in sex chromosomes than autosomes

“…The high r values in Sceloporus are due to the centromeric peaks of crossover distribution, in contrast with Anolis , which demonstrate mostly distally located crossovers. As shown by Veller et al, [16], median crossovers contribute much more to the effective recombination rate than the distal ones. It is highly unusual for vertebrates to have crossover peaks near the centromeres: the more common pattern is a reduction of crossover rate in the centromeric regions, which is called the “centromere effect” [43].…”

“…To check the hypothesis on the connection between chromosome fusion and evolution of recombination patterns, we applied an immunocytological approach to detect meiotic crossing over in synaptonemal complex (SC) spreads of S. malachiticus and S. variabilis , a related species with the unaltered ancestral karyotype (2n=34), and analyzed the recombination patterns using the r parameter [16]. This parameter is designed to measure recombination rate in meiosis by taking account of chromosome number, crossover number and crossover location.…”

Conservation of the genome-wide recombination rate in white-footed mice

“…Normalized foci positions (position/SC length) were compared by categorizing chromosome 1 bivalents into single- and double-focus (crossover) classes, grouping into 5% bins, and applying a Kolmogorov–Smirnov test. In addition to our comparison of the normalized foci positions, we calculated the intra-chromosomal portion of (Veller et al 2019) to compare how evenly crossovers were spaced while accounting for raw SC length. This metric ranges from 0 to 0.5, with higher values indicating that SC proportions flanking crossovers are more equivalent.…”