van der Kuyl Antoinette Cornelia
Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Amsterdam Institute for Immunology & Infectious Diseases, 1100 DD, Amsterdam, The Netherlands.
J Mol Evol. 2025 Feb;93(1):62-82. doi: 10.1007/s00239-024-10225-5. Epub 2024 Dec 23.
The time of integration of germline-targeting Long Terminal Repeat (LTR) retroposons, such as endogenous retroviruses (ERVs), can be estimated by assessing the nucleotide divergence between the LTR sequences flanking the viral genes. Due to the viral replication mechanism, both LTRs are identical at the moment of integration, when the provirus becomes part of the host genome. After that time, proviral sequences evolve within the host DNA. When the mutation rate is known, nucleotide divergence between the LTRs would then be a measure of time elapsed since integration. Though frequently used, the approach has been complicated by the choice of host mutation rate and, to a lesser extent, by the method selected to estimate nucleotide divergence. As a result, outcomes can be incompatible with, for instance, speciation events identified from the fossil record. The review will give an overview of research reporting LTR-retroposon dating, and a summary of important factors to consider, including the quality, assembly, and alignment of sequences, the mutation rate of foreign DNA in host genomes, and the choice of a distance estimation method. Primates will here be the focus of the analysis because their genomes, ERVs, and fossil record have been extensively studied. However, most of the factors discussed have a wide applicability in the vertebrate field.
通过评估病毒基因两侧长末端重复序列（LTR）之间的核苷酸差异，可以估算种系靶向性长末端重复（LTR）逆转座子（如内源性逆转录病毒，ERV）的整合时间。由于病毒复制机制，在原病毒成为宿主基因组的一部分时，两个LTR在整合瞬间是相同的。在那之后，原病毒序列在宿主DNA中进化。当突变率已知时，LTR之间的核苷酸差异将成为自整合以来经过时间的一个度量。尽管该方法经常被使用，但由于宿主突变率的选择，以及在较小程度上由于用于估计核苷酸差异的方法，使得该方法变得复杂。因此，结果可能与例如从化石记录中确定的物种形成事件不相符。本综述将概述报告LTR逆转座子年代测定的研究，并总结需要考虑的重要因素，包括序列的质量、组装和比对、宿主基因组中外源DNA的突变率以及距离估计方法的选择。灵长类动物将成为分析的重点，因为它们的基因组、ERV和化石记录都已得到广泛研究。然而，所讨论的大多数因素在脊椎动物领域具有广泛的适用性。
