Homologous Recombination Occurs Between Synapsed Chromosomes in Meiosis

KEY CONCEPTS
- Chromosomes must synapse (pair) in order for chiasmata to form where crossing-over occurs.
- The stages of meiosis can be correlated with the molecular events at the DNA level.
 Homologous recombination is a reaction between two duplexes of DNA. Its critical feature is that the enzymes responsible can use any pair of homologous sequences as substrates (although some types of sequences may be favored over others). In fact, in most species a crossover event is required for accurate separation of homologs at the first meiotic division; thus there is usually at least one crossover per homologous chromosome pair. The frequency of recombination is not constant throughout the genome, but is influenced by both global and local effects, and both recombination hotspots and coldspots can be identified. The short region of homology between the mammalian X and Y chromosomes (the “pseudoautosomal” region) is the only available region of crossover between the X and Y, and thus is subject to 10 times higher rates of crossover per length than the average for the rest of the genome. The phenomenon of crossover interference refers to the tendency (but not a rule) of a crossover event to reduce the likelihood of another crossover nearby. Crossovers are also rare in or near centromeres, are uncommon near telomeres in some species, and are generally suppressed in heterochromatic regions.

Certain histone modifications can also influence recombination positively or negatively. The overall frequency of recombination may be different in oocytes and in sperm; recombination occurs twice as frequently in female as in male humans.
Recombination occurs during the protracted prophase of meiosis. FIGURE 1. shows the visible progress of chromosomes through the five stages of meiotic prophase. Studies in yeast have shown that all of the molecular events of homologous recombination are finished by late pachytene.

FIGURE 1. Recombination occurs during the first meiotic prophase. The stages of prophase are defined by the appearance of the chromosomes, each of which consists of two replicas (sister chromatids), although the duplicated state becomes visible only at the end.
The beginning of meiosis is marked by the point at which individual chromosomes become visible. Each of these chromosomes has replicated previously and consists of two sister chromatids, each of which contains a duplex DNA. The homologous chromosomes approach one another and begin to pair in one or more regions, forming bivalents. Pairing extends until the entire length of each chromosome is apposed with its homolog. The process is called synapsis or chromosome pairing. When the process is completed, the chromosomes are laterally associated in the form of a synaptonemal complex, which has a characteristic structure
in each species, although there is wide variation in the details between species.
Recombination between chromosomes involves a physical exchange of parts (achieved through a double-strand break on one chromatid to initiate recombination), formation of a joint molecule between the chromatids, and resolution to break the joint and form intact chromatids that have new genetic information. When the chromosomes begin to separate, they can be seen to be held together at discrete sites called chiasmata. The number and distribution of chiasmata parallel the features of genetic crossing over. Traditional analysis holds that a chiasma represents the crossing-over event. The chiasmata remain visible when the chromosomes condense and all four chromatids become evident.
What is the molecular basis for these events? Each sister chromatid contains a single DNA duplex, so each bivalent contains four duplex molecules of DNA. Recombination requires a mechanism that allows the duplex DNA of one sister chromatid to interact with the duplex DNA of a sister chromatid from the other chromosome. This reaction must be able to occur between any pair of corresponding sequences in the two molecules in a highly specific manner so that the material can be exchanged with precision at the level of the individual base pair.
We know of only one mechanism for nucleic acids to recognize one another on the basis of sequence: complementarity between single strands. If (at least) one strand displaces the corresponding strand in the other duplex, the two duplex molecules will be specifically connected at corresponding sequences. If the strand exchange is extended, a more extensive connection can occur between the duplexes.