Modulating Crossover Frequency and Interference for Obligate Crossovers inSaccharomyces cerevisiaeMeiosis.
Meiotic crossover frequencies show wide variation among organisms. But most organisms maintain at least one crossover per homolog pair (obligate crossover). InSaccharomyces cerevisiae, previous studies have shown crossover frequencies are reduced in the mismatch repair related mutantmlh3Δ and enhanced in a meiotic checkpoint mutantpch2Δ by up to twofold at specific chromosomal loci, but both mutants maintain high spore viability. We analyzed meiotic recombination events genome-wide inmlh3Δ,pch2Δ, andmlh3Δpch2Δ mutants to test the effect of variation in crossover frequency on obligate crossovers.mlh3Δ showed ∼30% genome-wide reduction in crossovers (64 crossovers per meiosis) and loss of the obligate crossover, but nonexchange chromosomes were efficiently segregated.pch2Δ showed ∼50% genome-wide increase in crossover frequency (137 crossovers per meiosis), elevated noncrossovers as well as loss of chromosome size dependent double-strand break formation. Meiotic defects associated withpch2∆did not cause significant increase in nonexchange chromosome frequency. Crossovers were restored to wild-type frequency in the double mutantmlh3Δpch2Δ (100 crossovers per meiosis), but obligate crossovers were compromised. Genetic interference was reduced inmlh3Δ,pch2Δ, andmlh3Δpch2Δ. Triple mutant analysis ofmlh3Δpch2Δ with other resolvase mutants showed that most of the crossovers inmlh3Δpch2Δ are made through the Mus81-Mms4 pathway. These results are consistent with a requirement for increased crossover frequencies in the absence of genetic interference for obligate crossovers. In conclusion, these data suggest crossover frequencies and the strength of genetic interference in an organism are mutually optimized to ensure obligate crossovers.
School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Trivandrum 695016, India.
Parijat
P
Chakraborty
School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Trivandrum 695016, India.
Ajith V
AV
Pankajam
Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Gen
G
Lin
School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Trivandrum 695016, India.
Abhishek
A
Dutta
School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Trivandrum 695016, India.
Nandanan G
GN
Krishnaprasad
Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Manu M
MM
Tekkedil
Institute for Protein Research, Osaka University, 565-0871, Japan.
Akira
A
Shinohara
Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.|Department of Genetics, Stanford University, California 94305.|Stanford Genome Technology Center, Palo Alto, California 94304.
Lars M
LM
Steinmetz
School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Trivandrum 695016, India nishantkt@iisertvm.ac.in.|Center for Computation, Modelling and Simulation, Indian Institute of Science Education and Research, Thiruvananthapuram, Trivandrum 695016, India.
K T
KT
Nishant
D003434:Crossing Over, Genetic; D017353:Gene Deletion; D008540:Meiosis / Q000235:genetics*; D000070956:MutL Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
C492408:MLH3 protein, S cerevisiae; D009687:Nuclear Proteins; C528119:Pch2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000070956:MutL Proteins
crossover assurance; crossover frequency; genetic interference; genome wide recombination map; meiotic chromosome segregation