Lactase persistence/persistent (LP), the ability to express the lactase enzyme in adults, is one of the most strongly selected phenotypes in humans. It is encoded by at least five genetic variants that have rapidly become widespread in various human populations. The underlying selective mechanism is not clear however, because dairy products in general are well tolerated in adults, even by lactase non‐persistence/persistent (LNP) individuals. Cultural adaptations to milk consumption, notably fermentation and transformation, which can provide most of the energy (protein, (...) fat) to both LP and LNP individuals without any associated cost seem to have been common in ancient societies. Here, we propose that selection for LP occurred through increased glucose/galactose (energy) from fresh milk intake in early childhood, a crucial period for growth. At the age of weaning indeed, lactase activity has already begun to decline in LNP individuals so the gain in energy from fresh milk by LP children represents a major fitness increase. (shrink)

The ABO histo‐blood group, first discovered over a century ago, is found not only in humans but also in many other primate species, with the same genetic variants maintained for at least 20 million years. Polymorphisms in ABO have been associated with susceptibility to a large number of human diseases, from gastric cancers to immune or artery diseases, but the adaptive phenotypes to which the polymorphism contributes remain unclear. We suggest that variation in ABO has been maintained by frequency‐dependent or (...) fluctuating selection pressures, potentially arising from co‐evolution with gut pathogens. We further hypothesize that the histo‐blood group labels A, B, AB, and O do not offer a full description of variants maintained by natural selection, implying that there are unrecognized, functionally important, antigens beyond the ABO group in humans and other primates. (shrink)