title: A Pooled Sequencing Approach Identifies a Candidate Meiotic Driver inDrosophila.
abstract: Meiotic drive occurs when a selfish element increases its transmission frequency above the Mendelian ratio by hijacking the asymmetric divisions of female meiosis. Meiotic drive causes genomic conflict and potentially has a major impact on genome evolution, but only a few drive loci of large effect have been described. New methods to reliably detect meiotic drive are therefore needed, particularly for discovering moderate-strength drivers that are likely to be more prevalent in natural populations than strong drivers. Here, we report an efficient method that uses sequencing of large pools of backcross (BC1) progeny to test for deviations from Mendelian segregation genome-wide with single-nucleotide polymorphisms (SNPs) that distinguish the parental strains. We show that meiotic drive can be detected by a characteristic pattern of decay in distortion of SNP frequencies, caused by recombination unlinking the driver from distal loci. We further show that control crosses allow allele-frequency distortion caused by meiotic drive to be distinguished from distortion resulting from developmental effects. We used this approach to test whether chromosomes with extreme telomere-length differences segregate at Mendelian ratios, as telomeric regions are a potential hotspot for meiotic drive due to their roles in meiotic segregation and multiple observations of high rates of telomere sequence evolution. Using four different pairings of long and short telomere strains, we find no evidence that extreme telomere-length variation causes meiotic drive inDrosophilaHowever, we identify one candidate meiotic driver in a centromere-linked region that shows an ∼8% increase in transmission frequency, corresponding to a ∼54:46 segregation ratio. Our results show that candidate meiotic drivers of moderate strength can be readily detected and localized in pools of BC1 progeny.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853.
authors.forename: Kevin H-C
authors.initials: KH
authors.lastname: Wei
authors.affiliation: Laboratory of Genome Integrity and Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
authors.forename: Hemakumar M
authors.initials: HM
authors.lastname: Reddy
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853.
authors.forename: Chandramouli
authors.initials: C
authors.lastname: Rathnam
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853.
authors.forename: Jimin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853.
authors.forename: Deanna
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853.
authors.forename: Shuqing
authors.initials: S
authors.lastname: Ji
authors.affiliation: Laboratory of Genome Integrity and Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
authors.forename: James M
authors.initials: JM
authors.lastname: Mason
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Clark
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853 dab87@cornell.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Barbash
mesh_terms: D000818:Animals; D002503:Centromere / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics; D019143:Evolution, Molecular; D005787:Gene Frequency; D049750:Genome, Insect / Q000235:genetics*; D008540:Meiosis / Q000235:genetics*; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D016615:Telomere / Q000235:genetics
keywords: Drosophila; centromeres; drive; meiotic; telomeres