Klink Galya V, Kalinina Olga V, Bazykin Georgii A
Laboratory of Molecular Evolution, Institute for Information Transmission Problems (Kharkevich Institute) of the Russian Academy of Sciences, Bolshoy Karetny per. 19, build.1, Moscow 127051, Russia.
Center for Molecular and Cellular Biology, Skolkovo Institute of Science and Technology, Bolshoy Boulevard, 30, p.1, Skolkovo 121205, Russia.
Virus Evol. 2024 May 4;10(1):veae036. doi: 10.1093/ve/veae036. eCollection 2024.
Amino acid preferences at a protein site depend on the role of this site in protein function and structure as well as on external constraints. All these factors can change in the course of evolution, making amino acid propensities of a site time-dependent. When viral subtypes divergently evolve in different host subpopulations, such changes may depend on genetic, medical, and sociocultural differences between these subpopulations. Here, using our previously developed phylogenetic approach, we describe sixty-nine amino acid sites of the Gag protein of human immunodeficiency virus type 1 (HIV-1) where amino acids have different impact on viral fitness in six major subtypes of the type M. These changes in preferences trigger adaptive evolution; indeed, 32 (46 per cent) of these sites experienced strong positive selection at least in one of the subtypes. At some of the sites, changes in amino acid preferences may be associated with differences in immune escape between subtypes. The prevalence of an amino acid in a protein site within a subtype is only a poor predictor for whether this amino acid is preferred in this subtype according to the phylogenetic analysis. Therefore, attempts to identify the factors of viral evolution from comparative genomics data should integrate across multiple sources of information.
蛋白质位点上的氨基酸偏好取决于该位点在蛋白质功能和结构中的作用以及外部限制因素。所有这些因素在进化过程中都会发生变化，使得位点的氨基酸倾向具有时间依赖性。当病毒亚型在不同宿主亚群中发生趋异进化时，这种变化可能取决于这些亚群之间的遗传、医学和社会文化差异。在此，我们使用先前开发的系统发育方法，描述了人类免疫缺陷病毒1型（HIV-1）Gag蛋白的69个氨基酸位点，其中氨基酸对M型的六个主要亚型中的病毒适应性有不同影响。这些偏好的变化引发了适应性进化；实际上，这些位点中的32个（46%）至少在其中一个亚型中经历了强烈的正选择。在某些位点，氨基酸偏好的变化可能与亚型之间免疫逃逸的差异有关。根据系统发育分析，一个亚型内蛋白质位点上氨基酸的流行程度对于该氨基酸在该亚型中是否受偏好只是一个较差的预测指标。因此，从比较基因组学数据中识别病毒进化因素的尝试应整合多种信息来源。
