Abstract
The evolution of HIV during acute infection is often considered a neutral process. Recent analysis of sequencing data from this stage of infection, however, showed high levels of shared mutations between independent viral populations. This suggests that selection might play a role in the early stages of HIV infection. We adapted an existing model for random evolution during acute HIV-infection to include selection. Simulations of this model were used to fit a global mutational fitness effects distribution to previously published sequencing data of the env gene of individuals with acute HIV infection. Measures of sharing between viral populations were used as summary statistics to compare the data to the simulations. We confirm that evolution during acute infection is significantly different from neutral. The distribution of mutational fitness effects is best fit by a distribution with a low, but significant fraction of beneficial mutations and a high fraction of deleterious mutations. While most mutations are neutral or deleterious in this model, about 5% of mutations are beneficial. These beneficial mutations will, on average, result in a small but significant increase in fitness. When assuming no epistasis, this indicates that, at the moment of transmission, HIV is near, but not on the fitness peak for early infection.
Highlights
Evolution is driven by new mutations that cause a change in fitness of the organism
Measures of sharing between viral populations were used as summary statistics to compare the data to the simulations
The mutational fitness effects distribution (MFED, reviewed by Eyre-Walker and Keightley (2007)) captures how these effects are distributed for a certain organism in a certain environment
Summary
Evolution is driven by new mutations that cause a change in fitness of the organism. If a new mutation increases the reproductional success, or the fitness, this mutation is likely to be selected for and eventually fix in a population. Most mutations are not beneficial to the organism. Instead they are neutral—having no effect on fitness, or deleterious, reducing the amount of offspring compared with the ancestor. The effects a mutation can have on fitness lie on a continuum from completely lethal to beneficial, including viable but deleterious effects and neutral effects. The mutational fitness effects distribution (MFED, reviewed by Eyre-Walker and Keightley (2007)) captures how these effects are distributed for a certain organism in a certain environment
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have