Research has shown that modern-day humans and their extinct Neanderthal cousins differ by only a fraction of a percent. So what accounts for the differences that are known to exist between the two? In a ground-breaking new study published online in Science, scientists have discovered the cellular equivalent of on / off switches that determine which genes are activated or not.

Scientists have found that the genomes of Homo sapiens and Neanderthals are 99.84 percent genetically identical, and have fewer than 100 proteins that differ in their amino acid sequence. However, although numerous recent studies have shown that we are a lot more similar to Neanderthals than previously believed, there are still fundamental differences. For example, Neanderthals had shorter legs and arms, bowlegs, larger hands and fingers, curved arm bones, and more prominent brows. There are also a number of diseases and neurological conditions that have been found in humans but not Neanderthals. Could all these differences really be contained within a 0.12 percent difference?

Computational biologists Liran Carmel and stem cell biologist Eran Meshorer, at the Hebrew University of Jerusalem, and their team sought to answer this question by examining differences in the epigenomes of humans and Neanderthals, as well as the ancient hominid species known as the Denisovans. The genome is the sequence of 3 billion molecules that constitute all of a person's DNA while the epigenome is which bits of DNA are turned on or off even as the molecular sequence remains unchanged. For example, it is the epigenome that can account for difference traits between identical twins.

Their results revealed around 2,200 regions that were activated in today's humans, but silenced in either or both ancient species, or vice versa. When a gene is silenced, it does not produce the trait it otherwise would. In other words, differences between the species could be accounted for by on / off patterns in the DNA.

One of the major epigenetic differences was related to those that influence the shape and size of limbs. There were also significant differences in the on / off patterns between Neanderthals, Denisovans, and modern humans associated with neurological and psychiatric disorders including autism, schizophrenia and Alzheimer's disease. More of the Neanderthal and Denisovan versions were silenced, while the human versions were active.

However, the scientists acknowledged that the research technique is not without its limitations. Each individual’s epigenome can vary markedly from another’s due to diet, environment, and other factors. It is therefore impossible to know whether the on/off patterns found in Neanderthal genes are typical of the species overall or peculiar to the individual studied. Furthermore, epigenomes can vary between different tissues of the body, so epigenomes gathered from bone, hair, or teeth, will not necessarily say anything about the brain.

Nevertheless, the new method employed in this study is a first step towards further understanding the differences between modern-day humans and our ancient ancestors. As techniques and methods develop, there is promise that we may one day hold all the answers.

Featured image: Comparison of Neanderthal and Modern Human skeletons. Credit: K. Mowbray, Reconstruction: G. Sawyer and B. Maley, Copyright: Ian Tattersall

By April Holloway