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With the development of agriculture and food processing techniques, humanity has recently challenged the rules of a billion-year-old experiment called evolution. In this experiment the availability of food in a particular niche has been one of the major driving forces to shape particular species. Comparative genomics is a new research discipline that investigates two or more genomes from different species in order to find specific genetic adaptations that explain a 'workable match' between genetic make-up and environmental constraints such as nutrition. Three recent examples in the literature illustrate how selection of particular genes can contribute to species-specific adaptations that allow them to recognise, secure and digest particular types of food and metabolise its ingredients. There is growing consensus that the recent changes in human diet and physical activity play an active role in the rapid growth of the prevalence of obesity and diabetes. The working hypothesis of the present article is that in the future a more advanced level of comparative genomics of the many natural workable matches of natural species will lead to a much better understanding of the dynamics and regulation of integrated metabolism. It is anticipated that this deeper understanding will lead to novel insights into the mechanism of human diabetes and new strategies for diabetes prevention and treatment. This is one of a series of commentaries under the banner '50 years forward', giving personal opinions on future perspectives in diabetes, to celebrate the 50th anniversary of Diabetologia (1965-2015).

Comparative genomics: beyond the horizon of the next research grant