Mutational and transcriptional landscape of spontaneous gene duplications and deletions in Caenorhabditis elegans
Mutational and transcriptional landscape of spontaneous gene duplications and deletions in Caenorhabditis elegans
复制标题
DOI：
10.1073/pnas.1801930115
复制
发表时间：
2018-07-10
影响因子：
11.1
通讯作者：
Katju, Vaishali
中科院分区：
文献类型：
--
作者：
Konrad, Anke;Flibotte, Stephane;Katju, Vaishali
基因复制和缺失是基因组结构和功能的关键过程，对疾病、适应和进化都有影响。我们采用了突变积累（MA）的框架与高通量基因组学合作，以评估新出现的基因拷贝数变异（CNVs）的分子和转录特征的秀丽隐杆线虫种群进行不同强度的选择。在这里，我们报道了一个直接自发的基因组范围内的基因复制率为2.9 × 10（-5）/基因每一代在C。是迄今为止所有物种中最高的。基因缺失率低6倍（每代5 × 10（-6）/基因）。高表达基因的缺失是特别有害的，因为即使在具有最小选择效力的N = 1品系中它们也很少。在最小选择下产生的新的重复的平均转录丰度的增加是显着大于两倍相比，相同的基因的单拷贝，这表明在节段性重复的基因往往是过度活跃的开始。基因重复的转录活性的平均增加在N = 1 MA系中比在具有较大群体瓶颈的MA系中更大。新基因重复的祖先转录水平与种群规模之间存在反比关系，高表达基因的重复拷贝不太可能在较大的种群中积累。我们的结果表明，重复后转录增加的适应度成本，这导致针对新基因重复的纯化选择。然而，平均而言，复制也提供了基因表达的显着增加，可以促进适应新的环境挑战。
Gene duplication and deletion are pivotal processes shaping the structural and functional repertoire of genomes, with implications for disease, adaptation, and evolution. We employed a mutation accumulation (MA) framework partnered with high-throughput genomics to assess the molecular and transcriptional characteristics of newly arisen gene copy-number variants (CNVs) in Caenorhabditis elegans populations subjected to varying intensity of selection. Here, we report a direct spontaneous genome-wide rate of gene duplication of 2.9 x 10(-5)/gene per generation in C. elegans, the highest for any species to date. The rate of gene deletion is sixfold lower (5 x 10(-6)/gene per generation). Deletions of highly expressed genes are particularly deleterious, given their paucity in even the N = 1 lines with minimal efficacy of selection. The increase in average transcript abundance of new duplicates arising under minimal selection is significantly greater than twofold compared with single copies of the same gene, suggesting that genes in segmental duplications are frequently overactive at inception. The average increase in transcriptional activity of gene duplicates is greater in the N = 1 MA lines than in MA lines with larger population bottlenecks. There is an inverse relationship between the ancestral transcription levels of new gene duplicates and population size, with duplicate copies of highly expressed genes less likely to accumulate in larger populations. Our results demonstrate a fitness cost of increased transcription following duplication, which results in purifying selection against new gene duplicates. However, on average, duplications also provide a significant increase in gene expression that can facilitate adaptation to novel environmental challenges.