Whitelaw E, Martin D I
Department of Biochemistry, University of Sydney, Sydney, New South Wales, Australia.
Nat Genet. 2001 Apr;27(4):361-5. doi: 10.1038/86850.
Phenotypic variation in mammals is frequently attributed to the action of quantitative trait loci (QTL) or the environment, but may also be epigenetic in origin. Here we consider a mechanism for phenotypic variation based on interference of transcription by somatically active retrotransposons. Transcriptionally competent retrotransposons may number in the tens of thousands in mammalian genomes. We propose that silencing of retrotransposons occurs by cosuppression during early embryogenesis, but that this process is imperfect and produces a mosaic pattern of retrotransposon expression in somatic cells. Transcriptional interference by active retrotransposons perturbs expression of neighboring genes in somatic cells, in a mosaic pattern corresponding to activity of each retrotransposon. The epigenotype of retrotransposon activity is reset in each generation, but incomplete resetting can lead to heritable epigenetic effects. The stochastic nature of retrotransposon activity, and the very large number of genes that may be affected, produce subtle phenotypic variations even between genetically identical individuals, which may affect disease risk and be heritable in a non-mendelian fashion.
哺乳动物的表型变异通常归因于数量性状基因座（QTL）的作用或环境，但也可能源于表观遗传。在这里，我们考虑一种基于体细胞活跃反转录转座子对转录的干扰而产生表型变异的机制。在哺乳动物基因组中，具有转录活性的反转录转座子数量可能数以万计。我们提出，反转录转座子在胚胎发育早期通过共抑制作用发生沉默，但这个过程并不完美，会在体细胞中产生反转录转座子表达的镶嵌模式。活跃的反转录转座子的转录干扰会以与每个反转录转座子活性相对应的镶嵌模式扰乱体细胞中邻近基因的表达。反转录转座子活性的表观基因型在每一代中都会重置，但重置不完全会导致可遗传的表观遗传效应。反转录转座子活性的随机性以及可能受影响的大量基因，即使在基因相同的个体之间也会产生细微的表型变异，这可能会影响疾病风险并以非孟德尔方式遗传。
