Dept. of Evolutionary and Environmental Biology, University of Haifa, Haifa, 3498838, Israel.
BMC Genomics. 2020 Mar 5;21(Suppl 1):106. doi: 10.1186/s12864-019-6395-5.
Horizontal gene transfer (HGT) is the event of a DNA sequence being transferred between species not by inheritance. HGT is a crucial factor in prokaryotic evolution and is a significant source for genomic novelty resulting in antibiotic resistance or the outbreak of virulent strains. Detection of HGT and the mechanisms responsible and enabling it, is hence of prime importance.Existing algorithms rely on a strong phylogenetic signal distinguishing the transferred sequence from its recipient genome. Closely related species pose an even greater challenge as most genes are very similar and therefore, the phylogenetic signal is weak anyhow. Notwithstanding, the importance of detecting HGT between such organisms is extremely high for the role of HGT in the emergence of new highly virulent strains.
In a recent work we devised a novel technique that relies on loss of synteny around a gene as a witness for HGT. We used a novel heuristic for synteny measurement, SI (Syntent Index), and the technique was tested on both simulated and real data and was found to provide a greater sensitivity than other HGT techniques. This synteny-based approach suffers low specificity, in particular more closely related species. Here we devise an adaptive approach to cope with this by varying the criteria according to species distance. The new approach is doubly adaptive as it also considers the lengths of the genes being transferred. In particular, we use Chernoff bound to decree HGT both in simulations and real bacterial genomes taken from EggNog database.
Here we show empirically that this approach is more conservative than the previous χ based approach and provides a lower false positive rate, especially for closely related species and under wide range of genome parameters.
水平基因转移(HGT)是指一个 DNA 序列在物种之间通过遗传以外的方式转移。HGT 是原核生物进化的关键因素,也是导致抗生素耐药性或毒性菌株爆发的基因组新颖性的重要来源。因此,检测 HGT 及其负责和使其成为可能的机制至关重要。现有的算法依赖于一个强大的系统发育信号,该信号将转移的序列与其受体基因组区分开来。密切相关的物种构成了更大的挑战,因为大多数基因非常相似,因此,无论如何,系统发育信号都很弱。尽管如此,检测此类生物体之间的 HGT 非常重要,因为 HGT 在新的高毒性菌株的出现中起着重要作用。
在最近的一项工作中,我们设计了一种新的技术,该技术依赖于基因周围的同线性丧失作为 HGT 的证据。我们使用了一种新的同线性测量启发式方法 SI(同线性指数),并且该技术在模拟和真实数据上进行了测试,发现它比其他 HGT 技术具有更高的灵敏度。这种基于同线性的方法特异性较低,特别是对于更密切相关的物种。在这里,我们设计了一种自适应方法来应对这种情况,根据物种距离来改变标准。新方法是双重自适应的,因为它还考虑了要转移的基因的长度。特别是,我们使用 Chernoff 边界来裁定模拟和从 EggNog 数据库中获取的真实细菌基因组中的 HGT。
在这里,我们从经验上表明,这种方法比以前基于 χ 的方法更保守,并且提供了更低的假阳性率,特别是对于密切相关的物种和广泛的基因组参数。