Meiotic Recombination: The Essence of Heredity

Abstract

The study of homologous recombination has its historical roots in meiosis. In this context, recombination occurs as a programmed event that culminates in the formation of crossovers, which are essential for accurate chromosome segregation and create new combinations of parental alleles. Thus, meiotic recombination underlies both the independent assortment of parental chromosomes and genetic linkage. This review highlights the features of meiotic recombination that distinguish it from recombinational repair in somatic cells, and how the molecular processes of meiotic recombination are embedded and interdependent with the chromosome structures that characterize meiotic prophase. A more in-depth review presents our understanding of how crossover and noncrossover pathways of meiotic recombination are differentiated and regulated. The final section of this review summarizes the studies that have defined defective recombination as a leading cause of pregnancy loss and congenital disease in humans.

Figure 1.

Model of meiotic recombination. Schematic diagram showing the DNA intermediates of meiotic recombination highlighting the major pathways and key transitions (for more comprehensive models, see Martini et al. 2011; Kaur et al. 2015; Tang et al. 2015). Magenta lines indicate new DNA synthesis. During double-Holliday junction (dHJ) formation along the crossover branch, only one possible mechanism for engagement of the second double-strand break repair (DSB) end is shown, involving end-first displacement of the extended invading strand and annealing (Allers and Lichten 2001b; Lao et al. 2008). Alternative models include annealing of the second DSB end to an expanded D-loop, or a second strand invasion analogous to the first DSB end (Szostak et al. 1983; Martini et al. 2011). Proteins implicated in each step are shown; prefixes indicate proteins specific to a given organism: At, Arabidopsis thaliana, Ce, Caenorhabditis elegans; Dm, Drosophila melanogaster; Sc, Saccharomyces cerevisiae; Sp, Schizosaccharomyces pombe (see main text for details). Accompanying images show surface-spread mouse spermatocyte nuclei at the corresponding prophase stages, immunostained for pertinent recombination factors. In all images, homolog axes are visualized using SYCP3 antibodies. MEI4 is a SPO11-accessory protein required for DSB formation (Kumar et al. 2010). PCNA, Proliferating cell nuclear antigen.

Figure 2.

Chromosomal events of meiosis. The main stages of meiosis are shown for a single pair of homologous chromosomes (green and purple lines). Black rings indicate cohesion complexes connecting the sister chromatids. The synaptonemal complex is indicated by the triple-dashed line located between the homologs. Gray disks represent the kinetochores. Spindle microtubules are shown as thin green lines. The Venus symbol indicates the dictyotene stage at which prophase arrests in females. The images on the left-hand side show the corresponding prophase-I stages in surface-spread mouse spermatocyte nuclei immunostained for homolog axes (SYCP3, green) and the central region of the synaptonemal complex (SYCP1, red, but appears orange because of signal overlap). The final image shows a metaphase-I nucleus stained with Giemsa.