Absent from DNA and protein: genomic characterization of nullomers and nullpeptides across functional categories and evolution.
Absent from DNA and protein: genomic characterization of nullomers and nullpeptides across functional categories and evolution.
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DOI：
10.1186/s13059-021-02459-z
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发表时间：
2021-08-25
期刊：
影响因子：
12.3
通讯作者：
Ahituv N
中科院分区：
文献类型：
--
作者：
Georgakopoulos-Soares I;Yizhar-Barnea O;Mouratidis I;Hemberg M;Ahituv N
零聚体和零肽分别是基因组或蛋白质组中缺失的短DNA或氨基酸序列。它们缺失的一个潜在原因可能是它们对生物体有有害影响。在这里，我们鉴定了30种真核生物基因组和蛋白质组中所有可能的零粒和零肽，并证明了这些序列中的很大一部分处于负选择状态。我们还确定了特定功能类别所特有的零子：编码序列、外显子、内含子、5'UTR、3'UTR、启动子，并表明编码序列和启动子的零子最有可能被选中。通过分析生命之树上的所有蛋白质序列，我们进一步确定了36,081个长度为6个氨基酸的肽，这些肽在任何已知生物中都不存在，称为引物。接下来，我们描述了所有可能导致人类基因组中零分子出现的单碱基对突变，观察到转座元件中特定零分子序列的突变数量明显高于预期，这可能是由于它们的抑制。我们还注释了由于自然发生的变异而出现的零值，并表明其中的一个子集可以用来区分不同的人群。对脊椎动物进化过程中零分子和零肽的分析表明，它们也可以用作系统发育分类器。我们提供了不同功能类别的零分子和零肽的目录，开发了系统研究它们的方法，并强调在其他分析中使用这些序列的可变性。在线版本包含补充材料，可在10.1186/s13059-021-02459-z找到。
Nullomers and nullpeptides are short DNA or amino acid sequences that are absent from a genome or proteome, respectively. One potential cause for their absence could be their having a detrimental impact on an organism. Here, we identify all possible nullomers and nullpeptides in the genomes and proteomes of thirty eukaryotes and demonstrate that a significant proportion of these sequences are under negative selection. We also identify nullomers that are unique to specific functional categories: coding sequences, exons, introns, 5′UTR, 3′UTR, promoters, and show that coding sequence and promoter nullomers are most likely to be selected against. By analyzing all protein sequences across the tree of life, we further identify 36,081 peptides up to six amino acids in length that do not exist in any known organism, termed primes. We next characterize all possible single base pair mutations that can lead to the appearance of a nullomer in the human genome, observing a significantly higher number of mutations than expected by chance for specific nullomer sequences in transposable elements, likely due to their suppression. We also annotate nullomers that appear due to naturally occurring variants and show that a subset of them can be used to distinguish between different human populations. Analysis of nullomers and nullpeptides across vertebrate evolution shows they can also be used as phylogenetic classifiers. We provide a catalog of nullomers and nullpeptides in distinct functional categories, develop methods to systematically study them, and highlight the use of variability in these sequences in other analyses The online version contains supplementary material available at 10.1186/s13059-021-02459-z.
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