The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
PLoS Genet. 2013 May;9(5):e1003330. doi: 10.1371/journal.pgen.1003330. Epub 2013 May 9.
When a duplicate gene has no apparent loss-of-function phenotype, it is commonly considered that the phenotype has been masked as a result of functional redundancy with the remaining paralog. This is supported by indirect evidence showing that multi-copy genes show loss-of-function phenotypes less often than single-copy genes and by direct tests of phenotype masking using select gene sets. Here we take a systematic genome-wide RNA interference approach to assess phenotype masking in paralog pairs in the Caenorhabditis elegans genome. Remarkably, in contrast to expectations, we find that phenotype masking makes only a minor contribution to the low knockdown phenotype rate for duplicate genes. Instead, we find that non-essential genes are highly over-represented among duplicates, leading to a low observed loss-of-function phenotype rate. We further find that duplicate pairs derived from essential and non-essential genes have contrasting evolutionary dynamics: whereas non-essential genes are both more often successfully duplicated (fixed) and lost, essential genes are less often duplicated but upon successful duplication are maintained over longer periods. We expect the fundamental evolutionary duplication dynamics presented here to be broadly applicable.
当一个重复基因没有明显的功能丧失表型时，通常认为由于与剩余的同源基因具有功能冗余，该表型已被掩盖。这一观点得到了间接证据的支持，即多拷贝基因表现出功能丧失表型的频率低于单拷贝基因，并且通过对选择基因集进行表型掩盖的直接测试也得到了支持。在这里，我们采用系统的全基因组 RNA 干扰方法来评估秀丽隐杆线虫基因组中同源基因对的表型掩盖。值得注意的是，与预期相反，我们发现表型掩盖对重复基因低敲低表型率的贡献很小。相反，我们发现非必需基因在重复基因中高度过表达，导致观察到的功能丧失表型率较低。我们进一步发现，来自必需和非必需基因的重复对具有相反的进化动态：虽然非必需基因更常成功复制（固定）和丢失，但必需基因复制的频率较低，但成功复制后，它们的维持时间更长。我们预计这里提出的基本进化复制动态将具有广泛的适用性。
