Speaker
Description
Numerous experimental evolution studies have suggested that adaptation rate of microbial populations evolving in stable environments decline over time. To investigate the characteristics of adaptation deceleration in a fast-evolving virus, we propagated HIV-1 in two human T-cell lines (MT-2 and MT-4) for approximately 4.8 years and tracked its genome evolution through next-generation sequencing. The curated whole-genome sequencing data can be accessed and explored via LTEEviz, an interactive web application. Time-resolved sequencing data indicated that despite constant fixation rate of 0.085 (MT-2) and 0.042 (MT-4) mutations per generation, the fixation kinetics of adaptive mutations changed considerably over time. The rate of fixation of adaptive parallel mutations decreased by 44% per 300 generations, while their conferred fitness gain diminished by 27% (MT-2) and 18% (MT-4) per every added adaptive mutation in their genetic background. Furthermore, we identified unique yet consistent patterns of sequence evolution among different regions of the HIV-1 genome: non-coding regions, essential for viral replication and packaging, appeared to be subject to the strongest positive selection, whereas pol and gag genes were subject to the strongest purifying selection. In contrast, nef and vpr accessory genes demonstrated patterns of random evolution, expected in the absence of selection. In line with this expectation, the evolving populations of HIV-1 acquired and fixed multiple loss-of-function mutations in nef and vpr. Additionally, the nef gene repeatedly underwent large deletions. In two populations, several independent deletions of varying lengths together removed approximately 400 bp (equivalent to 4.3% of the HIV-1 genome), exemplifying progressive genome shrinkage. These large nef deletions increased in frequency faster than expected under neutrality and in a length-dependent manner. Together, our results confirm that HIV-1 genomic evolution is characterized by a swift and substantial deceleration of adaptation, while highlighting genome shrinkage as one of the underlying adaptive mechanisms.
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