Acquisti Claudia, Poste George, Curtiss David, Kumar Sudhir
Center for Evolutionary Functional Genomics, Arizona State University, Tempe, Arizona, United States of America.
PLoS One. 2007 Oct 10;2(10):e1022. doi: 10.1371/journal.pone.0001022.
Nullomers are short DNA sequences that are absent from the genomes of humans and other species. Assuming that nullomers are the signatures of natural selection against deleterious sequences in humans, the use of nullomers in drug target identification, pesticide development, environmental monitoring, and forensic applications has been envisioned.
Here, we show that the hypermutability of CpG dinucleotides, rather than the natural selection against the nullomer sequences, is likely the reason for the phenomenal event of short sequence motifs becoming nullomers. Furthermore, many reported human nullomers differ by only one nucleotide, which reinforces the role of mutation in the evolution of the constellation of nullomers in populations and species. The known nullomers in chimpanzee, cow, dog, and mouse genomes show patterns that are consistent with those seen in humans.
The role of mutations, instead of selection, in generating nullomers cast doubt on the utility of nullomers in many envisioned applications, because of their dependence on the role of lethal selection on the origin of nullomers.
零聚体是人类和其他物种基因组中不存在的短DNA序列。假设零聚体是针对人类有害序列自然选择的标志，人们设想了在药物靶点识别、农药开发、环境监测和法医应用中使用零聚体。
在这里，我们表明，CpG二核苷酸的高突变性，而非针对零聚体序列的自然选择，可能是短序列基序成为零聚体这一显著现象的原因。此外，许多已报道的人类零聚体仅相差一个核苷酸，这强化了突变在群体和物种中零聚体组合进化中的作用。黑猩猩、牛、狗和小鼠基因组中已知的零聚体呈现出与人类中所见一致的模式。
突变而非选择在产生零聚体中的作用，对零聚体在许多设想应用中的效用提出了质疑，因为它们依赖于致死选择在零聚体起源中的作用。
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