The Genetic Architecture of Natural Variation in Recombination Rate in Drosophila melanogaster.
The Genetic Architecture of Natural Variation in Recombination Rate in Drosophila melanogaster.
复制标题
果蝇果蝇重组率自然变异的遗传结构。
DOI：
10.1371/journal.pgen.1005951
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发表时间：
2016-04
期刊：
影响因子：
4.5
通讯作者：
Singh ND
中科院分区：
文献类型：
--
作者：
Hunter CM;Huang W;Mackay TF;Singh ND
减数分裂重组在许多有性生殖的生物体中保证了适当的染色体分离。尽管具有这种重要的功能，但在分类群内部和不同分类群之间，重组率是高度可变的，而且这种变异的遗传基础仍然知之甚少。在这里，我们利用黑腹果蝇遗传参考小组（DGRP）的近交系的自然变异来绘制影响重组率的遗传变异。我们使用两步杂交方案和可见标记来测量205个DGRP系X染色体上33 cM间隔和3R染色体上20.4 cM间隔的重组率。虽然我们不能排除由于与本研究中使用的可见标记相关的活力效应而存在一些偏差，但我们发现系间的重组率存在约2倍的差异。有趣的是，我们进一步发现重组率在两个染色体间隔之间不相关。我们进行了一项全基因组关联研究，以确定在调查的两个区间中与重组率相关的遗传变异。我们完善了候选变异和与重组率变异相关的基因列表，并选择了20个基因进行功能评估。我们提出了强有力的证据，表明五个基因可能对黑腹龙重组率的自然变异有贡献；这些基因位于典型减数分裂重组途径之外。我们还发现沃尔巴克氏体感染对重组率有微弱的影响，并证实了染色体间效应。我们的研究结果突出了黑腹龙葵在重组率上的群体变异幅度，并暗示了新的遗传因素介导了这一数量性状的自然变异。在减数分裂过程中，同源染色体通过重组交换遗传物质。在大多数有性繁殖的物种中，染色体的正确分离需要重组。重组缺陷会产生染色体数量不正确的配子，这对生物体的适应性是毁灭性的。尽管重组在染色体分离中起着核心作用，但重组在种内和种间都是一个高度可变的过程。虽然很明显，这种变异至少部分是由遗传造成的，但导致物种内部和物种之间重组变异的特定基因在很大程度上仍然未知。在模式生物——黑腹果蝇中尤其如此。在这里，我们使用黑腹龙遗传参考小组来确定重组率的种群水平变异规模，并确定与这种变异显著相关的基因。我们估计了205个菌株中两条不同染色体的重组率。我们还使用全基因组关联作图来确定与重组率变异相关的遗传因素。我们发现两条染色体上的重组率是独立的性状。我们进一步发现，群体水平上的重组变异是由许多影响较小的位点介导的，并且导致重组率变异的基因不在已被充分表征的减数分裂重组途径之外。
Meiotic recombination ensures proper chromosome segregation in many sexually reproducing organisms. Despite this crucial function, rates of recombination are highly variable within and between taxa, and the genetic basis of this variation remains poorly understood. Here, we exploit natural variation in the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) to map genetic variants affecting recombination rate. We used a two-step crossing scheme and visible markers to measure rates of recombination in a 33 cM interval on the X chromosome and in a 20.4 cM interval on chromosome 3R for 205 DGRP lines. Though we cannot exclude that some biases exist due to viability effects associated with the visible markers used in this study, we find ~2-fold variation in recombination rate among lines. Interestingly, we further find that recombination rates are uncorrelated between the two chromosomal intervals. We performed a genome-wide association study to identify genetic variants associated with recombination rate in each of the two intervals surveyed. We refined our list of candidate variants and genes associated with recombination rate variation and selected twenty genes for functional assessment. We present strong evidence that five genes are likely to contribute to natural variation in recombination rate in D. melanogaster; these genes lie outside the canonical meiotic recombination pathway. We also find a weak effect of Wolbachia infection on recombination rate and we confirm the interchromosomal effect. Our results highlight the magnitude of population variation in recombination rate present in D. melanogaster and implicate new genetic factors mediating natural variation in this quantitative trait. During meiosis, homologous chromosomes exchange genetic material through recombination. In most sexually reproducing species, recombination is necessary for chromosomes to properly segregate. Recombination defects can generate gametes with an incorrect number of chromosomes, which is devastating for organismal fitness. Despite the central role of recombination for chromosome segregation, recombination is highly variable process both within and between species. Though it is clear that this variation is due at least in part to genetics, the specific genes contributing to variation in recombination within and between species remain largely unknown. This is particularly true in the model organism, Drosophila melanogaster. Here, we use the D. melanogaster Genetic Reference Panel to determine the scale of population-level variation in recombination rate and to identify genes significantly associated with this variation. We estimated rates of recombination on two different chromosomes in 205 strains of D. melanogaster. We also used genome-wide association mapping to identify genetic factors associated with recombination rate variation. We find that recombination rate on the two chromosomes are independent traits. We further find that population-level variation in recombination is mediated by many loci of small effect, and that the genes contributing to variation in recombination rate are outside of the well-characterized meiotic recombination pathway.