Dr Mahan Ghafari has been awarded a Wellcome Trust Early Career Fellowship, starting in 2025. The scheme provides funding for early career researchers to develop their independent research identity. Mahan’s research will focus on developing a systematic framework for reconstructing evolutionary histories of viruses with pandemic potential.
Researchers estimate when two groups of organisms diverged in evolution by using the concept of a ‘molecular clock’, which is based on the relatively constant rate of changes in DNA and protein sequences over time. Accurately estimating this rate is crucial for characterising an organism’s evolutionary dynamics, including for pathogens, and reconstructing their natural history, as the clock rate provides the time frame during which these changes are expected to have occurred. While modern sequencing software helps infer rates and dates of species divergence events, their use can lead to inaccurate estimates if the underlying assumptions behind the predictions are not carefully considered.
Having already developed models to address rate variations in RNA and DNA viruses across different timescales, Mahan now plans to develop methods to understand the biological and methodological factors which influence evolutionary rate estimates. The framework he establishes from this work will allow the quantification of the effects of various evolutionary forces — such as selection and recombination — as well as the weakening of clocklike evolutionary signals over longer periods due to sparse sampling on evolutionary rate estimates. Initially focusing on viral rate estimation and determining the onset of epidemics in human populations, the research will extend to tracing the origins of these viruses back to their animal reservoirs, offering insights into historical outbreak patterns and their future likelihoods.
This research will advance our understanding of virus evolutionary history, impacting public health by accurately determining the timing of outbreaks, identifying factors that influence viral evolutionary dynamics, and contributing to pandemic preparedness by uncovering the biological mechanisms behind the emergence of novel virus variants in humans and risk of zoonotic transmissions. Mahan said:
“Ultimately, the aim of my fellowship is to combine quantitative evolutionary theory with an understanding of the factors that influence pathogen evolutionary rates over time to address important public health questions. This includes accurately estimating the onset of epidemics, the emergence of novel variants of viruses with epidemic or pandemic potential in humans, and tracing their origins in nonhuman reservoirs.”
