The modern synthesis, developed in the middle of the 20th century, held firmly that no intentional forces were at play in evolutionary theory (a thorough review of the approach of the modern synthesis is available in Stoltzfus’s Mutations, Randomness and Evolution). However, this was based more on the philosophical outlook of the participants of the synthesis rather than the data available.

In a recent paper, we showed that one of the foundational precepts of the modern synthesis, that mutations are random with respect to fitness, is actually based on a misunderstanding of how older experiments apply in the DNA age. Essentially, the foundational experiments which are used to show that mutations are random with respect to fitness – the Luria-Delbruck and Lederberg experiments – were both designed before DNA was known to be the carrier of inherited information. These experiments could not even in theory establish whether or not mutations were random with respect to fitness, because the range of possible mutations (i.e., possible base pair modifications) was unknown. At most, these experiments showed that the mutations were random with respect to external fitness factors, but leave the possibility well open that mutations are non-random with respect to an organism’s overall fitness (of which external selection is merely one aspect). In fact, many modern experiments have given evidence that mutations are not random with respect to the internal fitness factors of the organism.

We show that understanding this distinction yields important theoretical, mathematical, and experimental impacts on how evolutionary biology is approached.

Bartlett, Jonathan. 2023. “Random with Respect to Fitness or External Selection? An Important but Often Overlooked Distinction.” Acta Biotheoretica 71(2).