Variation in crossing-over rates across chromosome 4 of Arabidopsis thaliana reveals the presence of meiotic recombination "hot spots".

Crossover (CO) is a key process for the accurate segregation of homologous chromosomes during the first meiotic division. In most eukaryotes, meiotic recombination is not homogeneous along the chromosomes, suggesting a tight control of the location of recombination events. We genotyped 71 single nucleotide polymorphisms (SNPs) covering the entire chromosome 4 of Arabidopsis thaliana on 702 F2 plants, representing 1404 meioses and allowing the detection of 1171 COs, to study CO localization in a higher plant. The genetic recombination rates varied along the chromosome from 0 cM/Mb near the centromere to 20 cM/Mb on the short arm next to the NOR region, with a chromosome average of 4.6 cM/Mb. Principal component analysis showed that CO rates negatively correlate with the G+C content (P = 3x10(-4)), in contrast to that reported in other eukaryotes. COs also significantly correlate with the density of single repeats and the CpG ratio, but not with genes, pseudogenes, transposable elements, or dispersed repeats. Chromosome 4 has, on average, 1.6 COs per meiosis, and these COs are subjected to interference. A detailed analysis of several regions having high CO rates revealed "hot spots" of meiotic recombination contained in small fragments of a few kilobases. Both the intensity and the density of these hot spots explain the variation of CO rates along the chromosome.

[1]  S. Keeney,et al.  Mechanism and control of meiotic recombination initiation. , 2001, Current topics in developmental biology.

[2]  H. Lehrach,et al.  A novel procedure for efficient genotyping of single nucleotide polymorphisms. , 2000, Nucleic acids research.

[3]  P. Kwok,et al.  Methods for genotyping single nucleotide polymorphisms. , 2003, Annual review of genomics and human genetics.

[4]  G. Copenhaver,et al.  Crossover Interference on Nucleolus Organizing Region-Bearing Chromosomes in Arabidopsis , 2005, Genetics.

[5]  L. Duret,et al.  Recombination drives the evolution of GC-content in the human genome. , 2004, Molecular biology and evolution.

[6]  G. Benson,et al.  Tandem repeats finder: a program to analyze DNA sequences. , 1999, Nucleic acids research.

[7]  J. Montoya-Burgos,et al.  Recombination explains isochores in mammalian genomes. , 2003, Trends in genetics : TIG.

[8]  T. Takano-Shimizu.  Local changes in GC/AT substitution biases and in crossover frequencies on Drosophila chromosomes. , 2001, Molecular biology and evolution.

[9]  The Arabidopsis Genome Initiative.  Analysis of the genome sequence of the flowering plant Arabidopsis thaliana , 2000, Nature.

[10]  P. Colombo,et al.  Chiasma interference is blind to centromeres1 , 1997, Heredity.

[11]  B. Charlesworth,et al.  Recombination and base composition: the case of the highly self-fertilizing plant Arabidopsis thaliana , 2004, Genome Biology.

[12]  B. Massy.  Distribution of meiotic recombination sites. , 2003 .

[13]  Peter Donnelly,et al.  Human recombination hot spots hidden in regions of strong marker association , 2005, Nature Genetics.

[14]  O. Loudet,et al.  Bay-0 × Shahdara recombinant inbred line population: a powerful tool for the genetic dissection of complex traits in Arabidopsis , 2002, Theoretical and Applied Genetics.

[15]  A. Clark,et al.  Local rates of recombination are positively correlated with GC content in the human genome. , 2001, Molecular biology and evolution.

[16]  A. Nicolas,et al.  Clustering of meiotic double-strand breaks on yeast chromosome III. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[17]  J. Dutheil,et al.  Recombination Difference between Sexes: A Role for Haploid Selection , 2005, PLoS biology.

[18]  D. Kaback,et al.  Chromosome size-dependent control of meiotic reciprocal recombination in Saccharomyces cerevisiae: the role of crossover interference. , 1999, Genetics.

[19]  G. Copenhaver,et al.  Assaying genome-wide recombination and centromere functions with Arabidopsis tetrads. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[20]  David Haussler,et al.  Comparative recombination rates in the rat, mouse, and human genomes. , 2004, Genome research.

[21]  L. Hurst,et al.  Small introns tend to occur in GC-rich regions in some but not all vertebrates. , 1999, Trends in genetics : TIG.

[22]  R. Last,et al.  Arabidopsis Map-Based Cloning in the Post-Genome Era , 2002, Plant Physiology.

[23]  M. Morgante,et al.  Corn and humans: recombination and linkage disequilibrium in two genomes of similar size. , 2004, Trends in genetics : TIG.

[24]  G. Copenhaver,et al.  Does Crossover Interference Count in Saccharomyces cerevisiae? , 2004, Genetics.

[25]  H. Dooner,et al.  Recombination occurs uniformly within the bronze gene, a meiotic recombination hotspot in the maize genome. , 1997, The Plant cell.

[26]  E. Sanchez-Moran,et al.  Variation in chiasma frequency among eight accessions of Arabidopsis thaliana. , 2002, Genetics.

[27]  Jones Gh.  The control of chiasma distribution. , 1984 .

[28]  C. Lister,et al.  Recombinant inbred lines for mapping RFLP and phenotypic markers in Arabidopsis thaliana , 1993 .

[29]  J. Higgins,et al.  The Arabidopsis MutS homolog AtMSH4 functions at an early step in recombination: evidence for two classes of recombination in Arabidopsis. , 2004, Genes & development.

[30]  C. Dean,et al.  Integrated Cytogenetic Map of Chromosome Arm 4S of A. thaliana Structural Organization of Heterochromatic Knob and Centromere Region , 2000, Cell.

[31]  I. Gut,et al.  Automation in genotyping of single nucleotide polymorphisms , 2001, Human mutation.

[32]  M. Doutriaux,et al.  Two Meiotic Crossover Classes Cohabit in Arabidopsis One Is Dependent on MER3,whereas the Other One Is Not , 2005, Current Biology.

[33]  J. Bailey,et al.  Patterns of meiotic recombination on the long arm of human chromosome 21. , 2000, Genome research.

[34]  A. Nicolas,et al.  Association of Mre11p with double-strand break sites during yeast meiosis. , 2004, Molecular cell.

[35]  Michael Black,et al.  Role of transposable elements in heterochromatin and epigenetic control , 2004, Nature.

[36]  D. Gudbjartsson,et al.  A high-resolution recombination map of the human genome , 2002, Nature Genetics.

[37]  P. Deloukas,et al.  Comparison of human genetic and sequence-based physical maps , 2001, Nature.

[38]  F. Stahl,et al.  Crossover interference in humans. , 2003, American journal of human genetics.

[39]  S. Keeney,et al.  Where the crossovers are: recombination distributions in mammals , 2004, Nature Reviews Genetics.

[40]  M. Cotton,et al.  Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana , 1999, Nature.

[41]  S. Wright,et al.  Effects of recombination rate and gene density on transposable element distributions in Arabidopsis thaliana. , 2003, Genome research.

[42]  P. Brown,et al.  Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[43]  P. Schnable,et al.  Molecular characterization of meiotic recombination across the 140-kb multigenic a1-sh2 interval of maize , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[44]  E. Esch.  Estimation of gametic frequencies from F2 populations using the EM algorithm and its application in the analysis of crossover interference in rice , 2005, Theoretical and Applied Genetics.

[45]  L. Duret,et al.  Does recombination improve selection on codon usage? Lessons from nematode and fly complete genomes , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[46]  Casey M. Bergman,et al.  Combined Evidence Annotation of Transposable Elements in Genome Sequences , 2005, PLoS Comput. Biol..

[47]  M. Nachman,et al.  Variation in recombination rate across the genome: evidence and implications. , 2002, Current opinion in genetics & development.

[48]  C. Lister,et al.  Isolation and mapping of a new set of 129 RFLP markers in Arabidopsis thaliana using recombinant inbred lines. , 1996, The Plant journal : for cell and molecular biology.

[49]  L. K. Anderson and S. M. Stack,et al.  Meiotic Recombination in Plants , 2002 .

[50]  G. Copenhaver,et al.  Crossover interference in Arabidopsis. , 2002, Genetics.

[51]  John A Birdsell,et al.  Integrating genomics, bioinformatics, and classical genetics to study the effects of recombination on genome evolution. , 2002, Molecular biology and evolution.

[52]  P. Schnable,et al.  Genetic recombination in plants. , 1998, Current opinion in plant biology.

[53]  D. Bouchez,et al.  Physical Map and Organization of Arabidopsis thaliana Chromosome 4 , 1995, Science.

[54]  J. Cherry,et al.  Arabidopsis thaliana: a model plant for genome analysis. , 1998, Science.

[55]  G. Haberer,et al.  Mapping of the nucleolus organizer region on chromosome 4 inArabidopsis thaliana , 1996, Molecular and General Genetics MGG.

[56]  N. Kleckner,et al.  Meiotic chromosomes: integrating structure and function. , 1999, Annual review of genetics.

[57]  C. Weil,et al.  Analysis of recombination sites within the maize waxy locus. , 1997, Genetics.

[58]  L. Duret,et al.  GC-content evolution in mammalian genomes: the biased gene conversion hypothesis. , 2001, Genetics.

[59]  S. Schwartz,et al.  Covariation of Synaptonemal Complex Length and Mammalian Meiotic Exchange Rates , 2002, Science.

[60]  Y. Sano,et al.  Analysis of intragenic recombination at wx in rice: correlation between the molecular and genetic maps within the locus. , 2000, Genome.

[61]  J. Merker,et al.  Context dependence of meiotic recombination hotspots in yeast: the relationship between recombination activity of a reporter construct and base composition. , 2002, Genetics.

[62]  T. Hassold,et al.  Variation in human meiotic recombination. , 2004, Annual review of genomics and human genetics.

[63]  N. M. Hollingsworth,et al.  The Mus81 solution to resolution: generating meiotic crossovers without Holliday junctions. , 2004, Genes & development.