Luzuriaga-Neira Agusto, Subramanian Krishnamurthy, Alvarez-Ponce David
Biology Department, University of Nevada, Reno, Reno, NV, 89557, USA.
Current address: Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Genome Biol Evol. 2022 Aug 10;14(8). doi: 10.1093/gbe/evac126.
Analyses in a number of organisms have shown that duplicated genes are less likely to be essential than singletons. This implies that genes can often compensate for the loss of their paralogs. However, it is unclear why the loss of some duplicates can be compensated by their paralogs, whereas the loss of other duplicates cannot. Surprisingly, initial analyses in mice did not detect differences in the essentiality of duplicates and singletons. Only subsequent analyses, using larger gene knockout datasets and controlling for a number of confounding factors, did detect significant differences. Previous studies have not taken into account the tissues in which duplicates are expressed. We hypothesized that in complex organisms, in order for a gene's loss to be compensated by one or more of its paralogs, such paralogs need to be expressed in at least the same set of tissues as the lost gene. To test our hypothesis, we classified mouse duplicates into two categories based on the expression patterns of their paralogs: "compensable duplicates" (those with paralogs expressed in all the tissues in which the gene is expressed) and "non-compensable duplicates" (those whose paralogs are not expressed in all the tissues where the gene is expressed). In agreement with our hypothesis, the essentiality of non-compensable duplicates is similar to that of singletons, whereas compensable duplicates exhibit a substantially lower essentiality. Our results imply that duplicates can often compensate for the loss of their paralogs, but only if they are expressed in the same tissues. Indeed, the compensation ability is more dependent on expression patterns than on protein sequence similarity. The existence of these two kinds of duplicates with different essentialities, which has been overlooked by prior studies, may have hindered the detection of differences between singletons and duplicates.
对许多生物体的分析表明，与单拷贝基因相比，复制基因成为必需基因的可能性更小。这意味着基因通常能够补偿其旁系同源基因的缺失。然而，目前尚不清楚为什么有些复制基因的缺失能够被其旁系同源基因补偿，而另一些则不能。令人惊讶的是，对小鼠的初步分析并未检测到复制基因和单拷贝基因在必需性上的差异。只有后续使用更大的基因敲除数据集并控制了一些混杂因素的分析才检测到显著差异。以往的研究没有考虑到复制基因表达的组织。我们推测，在复杂生物体中，为了使一个基因的缺失能够被一个或多个旁系同源基因补偿，这些旁系同源基因需要至少在与缺失基因相同的一组组织中表达。为了验证我们的推测，我们根据旁系同源基因的表达模式将小鼠复制基因分为两类：“可补偿复制基因”（其旁系同源基因在该基因表达的所有组织中都有表达）和“不可补偿复制基因”（其旁系同源基因并非在该基因表达的所有组织中都有表达）。与我们的推测一致，不可补偿复制基因的必需性与单拷贝基因相似，而可补偿复制基因的必需性则显著更低。我们的结果表明，复制基因通常能够补偿其旁系同源基因缺失，但前提是它们在相同组织中表达。实际上，补偿能力更多地取决于表达模式而非蛋白质序列相似性。这两种具有不同必需性的复制基因的存在，此前的研究一直未予重视，可能阻碍了对单拷贝基因和复制基因之间差异的检测。
