Some say that we are what we eat. While we, as individuals, may not want to be reduced to our mere metabolic functions and food preferences, science is increasingly compiling evidence showing how the evolution of our species has interacted with the availability of different kinds of nutrition to shape the genetic framework of our metabolism.

Sociobiology has long proposed hypotheses suggesting that inventions like the use of fire for cooking and the spear for hunting set us on the evolutionary path that led us away from the other great apes. The energy needed to allow the development of our abnormally large and complex brain, for instance, may have only become accessible when our more ape-like ancestors started treating food before putting it in their mouth. Harvard anthropologist Richard Wrangham has captured this thinking in his book published in 2009, Catching Fire: How Cooking Made Us Human.

At the time, critics felt that these theories were perhaps plausible stories but that there was very little hard evidence to support them. This situation has improved considerably with the success of the sequencing of ancient genomes, including Neanderthal, Denisovans, and humans from the Stone Age and the Bronze Age (Curr. Biol. (2014) 24, R295–R298). Thanks to comparative genomics and forensic analysis of the diets of long-vanished human populations, researchers can now establish how changes in lifestyle were followed by changes in the genes controlling our metabolism.

More than FADS
Several studies screening for gene variants that appeared to be associated with diet changes or with long-term adherence to selective diets have found the strongest signals in the family of the closely related FADS (fatty acid deacetylase) genes on chromosome 11, which are now known to have undergone positive selection at various stages of human history.

While the function of FADS3 remains to be established, FADS1 and FADS2 are known to code for enzymes catalysing rate-limiting steps in the endogenous synthesis of long-chain omega-3 fatty acids, like those found in fish oil, from medium-chain length precursors that we can obtain from plant oils. Vegetarians depend on these enzymes more than those who regularly eat fish. On the other hand, an over-achieving omega-3 pathway can distort the balance between omega-3 fatty acids and other kinds. These metabolic balances are important for brain development and the synthesis of hormones including growth hormone. Fatty acids account for around 60% of the dry weight of our brain and, compared with other biological tissues, the brain is significantly enriched in long-chain fatty acids like docosahexaenoic acid (DHA) and arachidonic acid (AA).

Rasika Mathias and colleagues at Johns Hopkins University at Baltimore (Maryland, USA) first noted a marked difference in the allele frequency of FADS genes between African Americans and European Americans. They went on to analyse the spread of FADS alleles within Africa and found what may be the earliest divergence of these genes, dating to the time when Homo sapiens expanded out of Africa into the rest of the world (PLoS One (2012), 7, e44926).

Their analyses found that a variant improving the synthesis of long-chain omega-3 fatty acids in the absence of a fish-rich diet originated in Africa around 84,000 years ago, before the out of Africa migration, and became predominant in the African population but not in the migrants heading to the other continents. The authors speculate that this genetic change enabled the population staying in Africa to expand across the entire continent, including arid places where no fish was available.

Conversely, populations living by the seaside and depending on marine sources for much of their nutrition would benefit from gene variants with very little endogenous omega-3 synthesis activity. Matteo Fumagalli from University College London, UK, with colleagues from Denmark and the USA analysed the FADS genes of the Inuit population in Greenland, which has been living there for around 1,000 years, but has lived a similar, ocean-based lifestyle in other parts of the Arctic for much longer (Science (2015) 349, 1343–1347). In line with the working hypothesis, the researchers found that the Inuit predominantly harboured gene variants that are well-adjusted to a fish-rich diet but would likely provide insufficient endogenous omega-3 synthesis if the carriers chose not to eat fish.