High mutational rates of large-scale duplication and deletion in Daphnia pulex.
High mutational rates of large-scale duplication and deletion in Daphnia pulex.
复制标题
DOI：
10.1101/gr.191338.115
复制
发表时间：
2016-01
期刊：
影响因子：
7
通讯作者：
Lynch M
中科院分区：
文献类型：
--
作者：
Keith N;Tucker AE;Jackson CE;Sung W;Lucas Lledó JI;Schrider DR;Schaack S;Dudycha JL;Ackerman M;Younge AJ;Shaw JR;Lynch M
了解全基因组的突变率和突变谱对于理解疾病的起源和驱动所有进化过程的遗传变异是必要的。在这里，我们提供了一个全基因组的突变率和光谱的分析，通过单独的突变积累（MA）实验在两个蚤状水蚤基因型。与大多数利用单倍体、纯合或自交系的MA研究不同，D.蚤类可以无减数分裂繁殖，同时保持天然杂合的二倍体基因组，允许捕获杂合状态下出现的基因组变化的全谱。虽然碱基替换突变率与其他多细胞真核生物相似（每代每个位点约4 × 10−9），但我们发现大规模（>100 kb）从头拷贝数变异（CNVs）的发生率相对于先前MA研究中观察到的显著升高。在这个实验中保持的杂合性允许基因转换过程的估计。虽然我们报告的大多数转换道长度与减数分裂过程产生的转换道长度相似，但我们也发现了指示有丝分裂过程的较大的转换道长度。MA系与自然分离物的比较表明，自然群体中的大多数大规模CNV都通过纯化选择被去除。这里观察到的突变与致病的、复杂的、大规模的CNVs有相似之处，从而表明在D. pulex作为一个系统，用于研究导致这种变化的过程。
Knowledge of the genome-wide rate and spectrum of mutations is necessary to understand the origin of disease and the genetic variation driving all evolutionary processes. Here, we provide a genome-wide analysis of the rate and spectrum of mutations obtained in two Daphnia pulex genotypes via separate mutation-accumulation (MA) experiments. Unlike most MA studies that utilize haploid, homozygous, or self-fertilizing lines, D. pulex can be propagated ameiotically while maintaining a naturally heterozygous, diploid genome, allowing the capture of the full spectrum of genomic changes that arise in a heterozygous state. While base-substitution mutation rates are similar to those in other multicellular eukaryotes (about 4 × 10−9 per site per generation), we find that the rates of large-scale (>100 kb) de novo copy-number variants (CNVs) are significantly elevated relative to those seen in previous MA studies. The heterozygosity maintained in this experiment allowed for estimates of gene-conversion processes. While most of the conversion tract lengths we report are similar to those generated by meiotic processes, we also find larger tract lengths that are indicative of mitotic processes. Comparison of MA lines to natural isolates reveals that a majority of large-scale CNVs in natural populations are removed by purifying selection. The mutations observed here share similarities with disease-causing, complex, large-scale CNVs, thereby demonstrating that MA studies in D. pulex serve as a system for studying the processes leading to such alterations.