Speaker
Description
Whether or not there is a limit to adaptation is one of the fundamental questions of evolutionary biology. To what degree can a viral population evolve to be fitter in a constant environment? In a long-term evolution experiment with HIV-1 in two T-cell lines (MT-2 and MT-4), we have been observing the accumulation of majority mutations and fixations at an almost constant rate for more than five years. This is particularly surprising because we conducted the evolution experiment without imposing any direct selection pressure on the virus. Here, we investigated if these mutational changes go hand in hand with fitness gains.
To this end, we experimentally determined relative fitness of evolved virus populations in competition assays against the ancestor population. The evolved populations could be distinguished from the ancestor by a mutation (T9528G) that fixed in all evolution lines by allele-specific qPCR. Fitness changes were estimated by fitting a virus dynamics model that described the competition between ancestor and evolved virus populations in the assay.
We found statistically significant increases in fitness from passage 100 to passage 500 in all four evolution lines when assayed in the same T-cell line in which they had evolved. We also found significant fitness increases when a virus population that had been evolved on MT-4 was assayed in MT-2. The fitness gains in MT-4 were significantly larger than those in MT-2.
In conclusion, the accumulation of mutations in the long-term HIV-1 evolution experiment are accompanied by fitness gains. These fitness gains appear to become smaller over the years, which may fore-shadow a decline in the mutation accumulation rate.
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