Wei Kevin H-C, Reddy Hemakumar M, Rathnam Chandramouli, Lee Jimin, Lin Deanna, Ji Shuqing, Mason James M, Clark Andrew G, Barbash Daniel A
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853.
Laboratory of Genome Integrity and Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Genetics. 2017 May;206(1):451-465. doi: 10.1534/genetics.116.197335. Epub 2017 Mar 3.
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 in However, 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.
减数分裂驱动发生在一个自私元件通过劫持雌性减数分裂的不对称分裂，使其传递频率高于孟德尔比率时。减数分裂驱动会引发基因组冲突，并可能对基因组进化产生重大影响，但目前仅描述了少数具有较大效应的驱动位点。因此，需要可靠检测减数分裂驱动的新方法，特别是用于发现中等强度的驱动因素，这类因素在自然种群中可能比强驱动因素更为普遍。在此，我们报告一种高效方法，该方法利用回交（BC1）后代的大量群体测序，通过区分亲本菌株的单核苷酸多态性（SNP）来测试全基因组范围内与孟德尔分离的偏差。我们表明，减数分裂驱动可通过SNP频率扭曲的特征性衰减模式检测到，这种衰减是由重组使驱动因素与远端位点解连锁所致。我们进一步表明，对照杂交可将减数分裂驱动引起的等位基因频率扭曲与发育效应导致的扭曲区分开来。我们采用这种方法来测试具有极端端粒长度差异的染色体是否以孟德尔比率分离，因为端粒区域由于其在减数分裂分离中的作用以及对端粒序列进化高发生率的多次观察，是减数分裂驱动的一个潜在热点。使用四种不同的长端粒和短端粒菌株配对，我们没有发现证据表明极端端粒长度变异会在……中导致减数分裂驱动。然而，我们在一个着丝粒连接区域鉴定出一个候选减数分裂驱动因素，其传递频率增加了约8%，对应于约54:46的分离比率。我们的结果表明，中等强度的候选减数分裂驱动因素可以很容易地在BC1后代群体中检测到并定位。
