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Meiotic recombination hot spots and cold spots

Key Points

  • Eukaryotic chromosomes have regions of high (hot spots)and low (cold spots) meiotic recombination. These distortions of the genetic maps complicate gene identification by positional cloning strategies.

  • Meiotic recombination in yeast (and probably other eukaryotes) is initiated by meiosis-specific double-stranded DNA breaks (DSBs).

  • In yeast, DSBs occur preferentially in regions of 'open' chromatin, and some hot spots require the binding of transcription factors, but not high levels of transcription. Hot spots are clustered in high G + C domains that often contain more than one preferred site for DSB formation. Telomeric and centromeric regions often have low levels of meiotic exchange.

  • In humans, regions of elevated recombination have been observed on several chromosomes. The location and strength of these 'hot' regions is often different in males and females. Several human hot spots have been mapped to kilobase resolution using linkage disequilibrium and sperm typing.

  • Covalent modification of histones affects gene expression, DNA replication and chromosome condensation. Various experimental observations indicate that these modifications might also influence the distribution of meiotic recombination events.

Abstract

Meiotic recombination events are distributed unevenly throughout eukaryotic genomes. This inhomogeneity leads to distortions of genetic maps that can hinder the ability of geneticists to identify genes by map-based techniques. Various lines of evidence, particularly from studies of yeast, indicate that the distribution of recombination events might reflect, at least in part, global features of chromosome structure, such as the distribution of modified nucleosomes.

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Figure 1: Double-stranded-break-repair model of recombination.
Figure 2: Global regulation of hot-spot activity.
Figure 3: Genetic mapping in the human genome.
Figure 4: Three types of recombination hot spot.
Figure 5: Hot-spot activity in a model chromosome.

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Acknowledgements

I thank J. Gerton, C. D. Allis, F. Winston, J. Kohli, G. Smith and M. Lichten for comments and suggestions on the manuscript. I was supported by the National Institutes of Health.

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DATABASE LINKS

Spo11

ARG4

HIS4

LEU2

rad50S

Bas1

Bas2

Gcn4

Rap1

Atf1

Mts1

RAD50

Swi6

CEN6

TAP2 (human)

Spo11

CARM1

Mec1

Rad6

Swi

Snf

FURTHER INFORMATION

Marshfield Clinic

Thomas Petes' lab

Glossary

GENE CONVERSION

The non-reciprocal transfer of information between homologous genes as a consequence of heteroduplex formation, followed by repair of mismatches in the heteroduplex. In current models of recombination, regions of potential gene conversion are associated with all crossovers.

HETERODUPLEX

A region of duplex DNA that contains strands derived from two different DNA molecules.

HOLLIDAY JUNCTION

When two DNA molecules exchange DNA strands (producing a heteroduplex), the point of the exchange is called a 'Holliday junction.'

LINKAGE DISEQUILIBRIUM

The condition in which the frequency of a particular haplotype for two loci is significantly greater than that expected from the product of the observed allelic frequencies at each locus.

MINISATELLITE

Regions of DNA in which repeat units of 10–50 base pairs are tandemly arranged in arrays 0.5–30 kb in length.

BROMODOMAIN

A protein motif (originally defined in the Drosophila Brahma protein) that is involved in binding certain acetylated histones; often associated with transcriptional activation.

CHROMODOMAIN

A protein motif that is involved in binding certain methylated histones; often associated with transcriptional repression.

CHECKPOINT

A position in the cell cycle at which progression can be arrested to complete a cellular function, such as the repair of DNA damage.

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Petes, T. Meiotic recombination hot spots and cold spots. Nat Rev Genet 2, 360–369 (2001). https://doi.org/10.1038/35072078

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  • DOI: https://doi.org/10.1038/35072078

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