Question

Phylogenetic trees built from DNA/protein sequences use sequence differences between these biological sequences as proxies for relatedness.

More specifically, maximum-likelihood phylogenetic trees (which are arguably the most commonly used/most accurate way to build phylogenetic trees) assume an evolutionary model (i.e. a way in which sequences diverge) and try to learn parameters that best explain the sequence divergence we see in our DNA/protein sequences.

In my mind, everything is clear and straight forward if you assume neutral evolution and constant mutation rates. Under this model, sequences will simply randomly mutate at a constant rate, and the more different two sequences are, the more distantly related they will be (on average, at least).

Now, what happens if we assume non-neutral, i.e. positive or negative selection? Can maximum-likelihood trees detect this? How do they handle this? Can they? Should we even build phylogenetic trees on sequences that evolve non-neutrally? I cannot wrap my head around

Answer 1

Phylogenetic trees built using maximum-likelihood methods can incorporate models of selection to handle non-neutral evolutionary pressures, but interpretation of these trees is more complex as they also depict the interplay of evolutionary forces, not just time-based divergence.

Step-by-step explanation:

Phylogenetic trees use molecular similarities to infer evolutionary relationships among species, assuming that the more similar the sequences are, the more closely related the organisms might be. However, when accounting for natural selection, such as positive or negative selection, the assumptions of neutral evolution and constant mutation rates inherent to methods like maximum-likelihood phylogenetic trees are disrupted. While maximum-likelihood methods can incorporate models of selection to some degree, it becomes challenging to discern evolutionary pathways when selection is acting on the sequences. This is because selected sequences may not mutate at constant rates and may show convergent features due to similar selective pressures rather than ancestry. Despite these challenges, non-neutral sequences can still be used to build phylogenetic trees by selecting the appropriate models and techniques that can handle selection pressures. Nonetheless, it is crucial to interpret such trees cautiously, as the relationships depicted may not simply reflect time but also the complex interplay of evolutionary forces.