Singh Nadia D, Aquadro Charles F, Clark Andrew G
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
J Mol Evol. 2009 Jul;69(1):42-53. doi: 10.1007/s00239-009-9250-5. Epub 2009 Jun 6.
Accurate assessment of local recombination rate variation is crucial for understanding the recombination process and for determining the impact of natural selection on linked sites. In Drosophila, local recombination intensity has been estimated primarily by statistical approaches, by estimating the local slope of the relationship between the physical and genetic maps. However, these estimates are limited in resolution and, as a result, the physical scale at which recombination intensity varies in Drosophila is largely unknown. Although there is some evidence suggesting as much as a 40-fold variation in crossover rate at a local scale in D. pseudoobscura, little is known about the fine-scale structure of recombination rate variation in D. melanogaster. Here we experimentally examine the fine-scale distribution of crossover events in a 1.2-Mb region on the D. melanogaster X chromosome using a classic genetic mapping approach. Our results show that crossover frequency is significantly heterogeneous within this region, varying approximately 3.5-fold. Simulations suggest that this degree of heterogeneity is sufficient to affect levels of standing nucleotide diversity, although the magnitude of this effect is small. We recover no statistical association between empirical estimates of nucleotide diversity and recombination intensity, which is likely due to the limited number of loci sampled in our population genetic data set. However, codon bias is significantly negatively correlated with fine-scale recombination intensity estimates, as expected. Our results shed light on the relevant physical scale to consider in evolutionary analyses relating to recombination rate and highlight the motivations to increase the resolution of the recombination map in Drosophila.
准确评估局部重组率变异对于理解重组过程以及确定自然选择对连锁位点的影响至关重要。在果蝇中,局部重组强度主要通过统计方法进行估计,即通过估计物理图谱与遗传图谱之间关系的局部斜率。然而,这些估计的分辨率有限,因此,果蝇中重组强度发生变化的物理尺度在很大程度上尚不清楚。尽管有一些证据表明,在拟暗果蝇中局部尺度上的交叉率变化高达40倍,但对于黑腹果蝇中重组率变异的精细结构却知之甚少。在这里,我们使用经典的遗传作图方法,通过实验研究了黑腹果蝇X染色体上一个1.2 Mb区域内交叉事件的精细分布。我们的结果表明,该区域内的交叉频率存在显著的异质性,变化幅度约为3.5倍。模拟结果表明,这种异质性程度足以影响固定核苷酸多样性水平,尽管这种影响的幅度较小。我们没有发现核苷酸多样性的经验估计值与重组强度之间存在统计关联,这可能是由于我们群体遗传数据集中采样的位点数量有限。然而,正如预期的那样,密码子偏好与精细尺度的重组强度估计值显著负相关。我们的结果揭示了在与重组率相关的进化分析中需要考虑的相关物理尺度,并强调了提高果蝇重组图谱分辨率的动机。