Beyond the Tick-Tock: Models for Genetic Time Travel Using Molecular Clocks
How Relaxed Phylogenetics Rewrites Genetic History
The following is a synopsis of the perspective article The dawn of relaxed phylogenetics by Steenwyk & Rokas (PLOS Biology, 2023).
The Quest for a Molecular Evolutionary Clock
In 1965, Emile Zuckerkandl and Linus Pauling proposed the idea of a "molecular evolutionary clock" to understand the timing of genetic changes in evolution. The rate of genetic change was initially assumed to be constant across species — a global clock. However, later studies revealed different organisms evolved at variable rates. This posed a problem for dating evolutionary relationships. To address this, researchers developed models that allowed for varying rates of evolution across branches in a phylogenetic tree.
Early attempts included "local molecular clocks" that required prior knowledge of which lineages had different evolutionary rates. Later, "autocorrelated relaxed clock models" were introduced, allowing rates to vary across branches based on the assumption that closely related species have similar rates. However, this method had challenges, especially among poorly supported branches, and support for the assumption that closely related species evolve at similar rates was lacking.
A Breakthrough in Estimation
In 2006, a groundbreaking study by Drummond and colleagues introduced a Bayesian Markov Chain Monte Carlo method that co-estimated phylogenies and divergence times, overcoming previous limitations. This "relaxed" approach considered different evolutionary rates for each branch, co-estimated substitution and relaxed clock parameters, and accounted for calibration uncertainties. This method was incorporated into the BEAST software.
Drummond and colleagues demonstrated the effectiveness of relaxed phylogenetics in accurately estimating phylogenies and divergence times across various lineages, including marsupial mammals. It also revealed that clock-like evolution is relatively rare in genes. This approach has since been used to study the evolution of pathogenic viruses, the timing of megafauna evolution, and human evolution.
Future Horizons and Closing Thoughts
The future of relaxed phylogenetics holds promise in terms of faster computation, enabling analysis of larger datasets, and reducing environmental costs. Machine learning and computer science advances may further enhance this method's capabilities. BEAST software, known for its user-friendliness and extensive resources, has significantly advanced evolutionary biology.
In conclusion, relaxed phylogenetics, introduced in the 2006 PLoS Biology article, revolutionized the field by providing a more accurate and biologically realistic way to estimate the timing and mode of genetic evolution. This method has led to significant discoveries and continues to shape our understanding of evolutionary relationships.