基因表达在中主要受基因剂量调控。

, a unicellular eukaryotic parasite present in North and East Africa, the Middle East, and the Indian subcontinent, has been linked to large outbreaks of cutaneous leishmaniasis in displaced populations in Iraq, Jordan, and Syria. Here, we report the genome sequence of this pathogen and 7,863 identified protein-coding genes, and we show that the majority of clinical isolates possess high levels of allelic diversity, genetic admixture, heterozygosity, and extensive aneuploidy. By utilizing paired genome-wide high-throughput DNA sequencing (DNA-seq) with RNA-seq, we found that gene dosage, at the level of individual genes or chromosomal "somy" (a general term covering disomy, trisomy, tetrasomy, etc.), accounted for greater than 85% of total gene expression variation in genes with a 2-fold or greater change in expression. High gene copy number variation (CNV) among membrane-bound transporters, a class of proteins previously implicated in drug resistance, was found for the most highly differentially expressed genes. Our results suggest that gene dosage is an adaptive trait that confers phenotypic plasticity among natural populations by rapid down- or upregulation of transporter proteins to limit the effects of environmental stresses, such as drug selection. is a genus of unicellular eukaryotic parasites that is responsible for a spectrum of human diseases that range from cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL) to life-threatening visceral leishmaniasis (VL). Developmental and strain-specific gene expression is largely thought to be due to mRNA message stability or posttranscriptional regulatory networks for this species, whose genome is organized into polycistronic gene clusters in the absence of promoter-mediated regulation of transcription initiation of nuclear genes. Genetic hybridization has been demonstrated to yield dramatic structural genomic variation, but whether such changes in gene dosage impact gene expression has not been formally investigated. Here we show that the predominant mechanism determining transcript abundance differences (>85%) in is that of gene dosage at the level of individual genes or chromosomal somy.

利什曼原虫，一种存在于北非、中东和印度次大陆的单细胞真核寄生虫，与伊拉克、约旦和叙利亚流离失所人群中大规模爆发的皮肤利什曼病有关。在这里，我们报告了这种病原体的基因组序列和 7863 个鉴定的蛋白质编码基因，我们表明大多数临床分离株具有高水平的等位基因多样性、遗传混合、杂合性和广泛的非整倍性。通过利用配对的全基因组高通量 DNA 测序（DNA-seq）和 RNA-seq，我们发现基因剂量，即在单个基因或染色体“somy”（涵盖非整倍体、三体、四倍体等的一般术语）水平上，占表达变化 2 倍或以上的基因的总基因表达变异的 85%以上。在表达水平变化 2 倍或以上的基因中，我们发现膜结合转运蛋白的高基因拷贝数变异（CNV），这是一类先前与耐药性相关的蛋白质。我们的研究结果表明，基因剂量是一种适应性特征，通过快速下调或上调转运蛋白来限制环境压力（如药物选择）的影响，从而在自然种群中赋予表型可塑性。

利什曼原虫是一种单细胞真核寄生虫属，可引起一系列人类疾病，从皮肤利什曼病（CL）和黏膜皮肤利什曼病（MCL）到危及生命的内脏利什曼病（VL）不等。该物种的发育和菌株特异性基因表达主要归因于 mRNA 消息的稳定性或转录后调控网络，其基因组在没有启动子介导的核基因转录起始调控的情况下组织成多顺反子基因簇。遗传杂交已被证明会产生巨大的结构基因组变异，但基因剂量的这种变化是否会影响基因表达尚未得到正式研究。在这里，我们表明，决定基因表达丰度差异（>85%）的主要机制是单个基因或染色体 somy 的基因剂量。