Evolution as a physical process on fitness landscapes

6 problems

• Accessibility of fitness peaks in large sequence spaces

  Partially resolved

  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.

• Distribution of fitness effects of beneficial mutations

  Contested

  Extreme-value statistics, the mathematics of the largest values in a random sample, predicts that rare improving mutations in a well-adapted organism follow a simple exponential law. Experiments give mixed support, and which statistical class real mutations follow is unsettled.

• Why diminishing-returns epistasis is so common

  Partially resolved

  In many experiments a beneficial mutation helps less in a fitter genome, as if all mutations interact through one shared fitness value. Whether this pattern emerges generically from many hidden molecular interactions, and when, is not settled.

• Why genetic diversity barely grows with population size

  Contested

  Simple theory says a species with a billion times more individuals should carry far more genetic variation, but diversity differs only about a hundredfold across animals whose numbers differ by more than ten orders of magnitude. What compresses diversity in large populations is unknown.

• How predictable and repeatable is evolution?

  Open

  If the same population evolved again from the same start, would it take the same steps and end in the same place? The answer depends on population size, mutation supply and the shape of the fitness surface, in ways not yet quantified.

• Does fitness in long-term evolution increase without limit?

  Open

  In an experiment running since 1988, twelve populations of E. coli have kept getting fitter for more than 70,000 generations. Whether their fitness approaches a ceiling or rises forever is open.