Image credit: Darryl Leja, National Human Genome Research Institute NIH (CC BY-NC 2.0)
Human chromosomes are made up of DNA, which contains about 3 billion ‘letters’ that carry the instructions needed to build and maintain an individual. However, only about 10 percent of the human genome is made up of genes that code for proteins, or have a defined role in the body. The DNA sequence is largely the same in all people, but some modifications – or variants – occur about every hundred letters. These produce different versions of the same gene, which give us our unique features, such as the color of our hair or eyes.
The frequencies of some genetic variants can change over time, which makes human populations diverge genetically and physically. This can happen through different mechanisms. Positive selection keeps variants that are beneficial in specific environments, while negative selection removes genetic changes that are detrimental, for example because they cause disease. Transmission bias favors one of the two variants from our two parents. Chance alters the frequencies of neutral variants, which are neither good nor bad for the individual.
It is important to distinguish between these different scenarios, as they inform us about the forces that act on human evolution. For example, neutral variants tell us about the demography and migration patterns between populations. Variants under negative selection reveal which genetic areas are under pressure to stay the same because they are important for the organism to function correctly. Until now, it was unclear how we could best identify the variants affected by different evolutionary pressures, and how much of the genome was under negative selection.
Pouyet, Aeschbacher et al. created a measure of genetic diversity that is only affected by selection or transmission bias. The results showed that negative selection influences as much as 85 percent of our genome, whereas transmission bias affects a majority of the rest of the genome. After removing these two biases, less than 5 percent of the human genome is found to evolve by chance. This suggests that while most of our genetic material is formed of non-functional sequences, the vast majority of it evolves indirectly under some type of selection.
These findings define which parts of our genome evolves neutrally and can therefore be used to correctly reconstruct the past demography and migration events of humans around the world. The next step could be to reassess the history of human populations that was drawn using genomic data.
