Mutation is the ultimate source of genetic variation, the bedrock of evolution. Yet, predicting the consequences of new mutations remains a challenge in biology. Gene expression provides a potential link between a genotype and its phenotype. But the variation in gene expression created by de novo mutation and the fitness consequences of mutational changes to expression remain relatively unexplored. Here, we investigate the effects of >2600 de novo mutations on gene expression across the transcriptome of 28 mutation accumulation lines derived from two independent wild-type genotypes of the green algae Chlamydomonas reinhardtii. We observed that the amount of genetic variance in gene expression created by mutation (Vm) was similar to the variance that mutation generates in typical polygenic phenotypic traits and approximately 15-fold the variance seen in the limited species where Vm in gene expression has been estimated. Despite the clear effect of mutation on expression, we did not observe a simple additive effect of mutation on expression change, with no linear correlation between the total expression change and mutation count of individual MA lines. We therefore inferred the distribution of expression effects of new mutations to connect the number of mutations to the number of differentially expressed genes (DEGs). Our inferred DEE is highly L-shaped with 95% of mutations causing 0-1 DEG while the remaining 5% are spread over a long tail of large effect mutations that cause multiple genes to change expression. The distribution is consistent with many cis-acting mutation targets that affect the expression of only one gene and a large target of trans-acting targets that have the potential to affect tens or hundreds of genes. Further evidence for cis-acting mutations can be seen in the overabundance of mutations in or near differentially expressed genes. Supporting evidence for trans-acting mutations comes from a 15:1 ratio of DEGs to mutations and the clusters of DEGs in the co-expression network, indicative of shared regulatory architecture. Lastly, we show that there is a negative correlation with the extent of expression divergence from the ancestor and fitness, providing evidence of the deleterious effects of perturbing gene expression.

中文翻译：

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从头突变对莱茵衣藻基因表达的影响及其适应性的后果

突变是遗传变异的最终根源，是进化的基石。然而，预测新突变的后果仍然是生物学中的一个挑战。基因表达提供了基因型与其表型之间的潜在联系。但从头突变引起的基因表达变异以及突变变化对表达的适应性影响仍然相对未被探索。在这里，我们研究了超过2600个从头突变对来自绿藻莱茵衣藻的两个独立野生型基因型的28个突变累积系的转录组中基因表达的影响。我们观察到，由突变（Vm）产生的基因表达的遗传方差量与典型多基因表型性状中突变产生的方差相似，并且是在估计基因表达中的 Vm 的有限物种中看到的方差的大约 15 倍。尽管突变对表达有明显的影响，但我们没有观察到突变对表达变化的简单累加效应，总表达变化与单个 MA 系的突变计数之间没有线性相关性。因此，我们推断了新突变的表达效应分布，将突变数量与差异表达基因（DEG）的数量联系起来。我们推断的 DEE 呈高度 L 形，其中 95% 的突变导致 0-1 DEG，而其余 5% 分布在大效应突变的长尾上，导致多个基因改变表达。该分布与仅影响一个基因表达的许多顺式作用突变靶点和可能影响数十或数百个基因的反式作用靶点的大靶点一致。顺式作用突变的进一步证据可以在差异表达基因中或附近的突变过多中看到。支持反式作用突变的证据来自 DEG 与突变的 15:1 比例以及共表达网络中的 DEG 簇，表明共享的调控架构。最后，我们表明，与祖先的表达分歧程度和适应性之间存在负相关，这提供了扰乱基因表达的有害影响的证据。