BIO On PubPhys: open In the literature: partially resolved Compiled by AI, not yet reviewed by an editor

Accessibility of fitness peaks in large sequence spaces

In plain words

For evolution to reach the best genome, there must be a route of single mutations along which fitness never decreases. How often such routes exist in real landscapes with many sites is unknown.

Precise statement

In random-field models (house-of-cards, rough Mount Fuji, NK), the number of fitness-monotonic paths from a genotype to the global optimum in a sequence space of $L$ sites (binary or four-letter) varies with $L$ in ways set by ruggedness, including path-percolation transitions. Determine from combinatorially complete or near-complete empirical landscapes ($L\ge10$ to 15 sites) which model class applies, and extrapolate the probability that the global peak is accessible as $L$ grows.

What would settle it

Complete fitness maps of at least 10 to 15 interacting sites with path statistics compared against the random-field model classes.

Status in the literature

A combinatorially complete $4^9$ DHFR landscape (2023) was rugged (514 peaks) yet its highest peaks were accessible (Science, doi 10.1126/science.adh3860); extrapolation to larger $L$ is open.

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