What Made Humans Better Than Neanderthals? Not Mutation, Say Scientists

Our genomes are 99% identical. It's a question of how evolution turned our genes on and off, notably genes relating to brain.

Ruth Schuster
Ruth Schuster
This Neanderthal skull may look alien, seen against a human one in the background. But we share genes for skin and hair, and other things too, it seems.
This Neanderthal skull may look alien, seen against a human one in the background. But we share genes for skin and hair, and other things too, it seems.Credit: AP
Ruth Schuster
Ruth Schuster

By now it's clear: modern man had intercourse with other species of humans, including – at the very least – Neanderthals and Denisovans, who had lived in Eurasia. Yet only homo sapiens survived. The reasons why remain exceedingly controversial, not to mention speculative, but now scientists in Jerusalem postulate that the success of mankind - as opposed to neanderkind - lay not in genetic changes, but in change in the way almost the same DNA was expressed.

Not genetics, but epigenetics: In other words, humans beat the competition not because of mutations in our genes that gave us a decisive advantage, but thanks to changes in how our genes were expressed, postulates a broad team of scientists from the Hebrew University of Jerusalem, Spain, and Germany.

"We found cases in which the gene is the same in humans and Neanderthals, but we find that this sthese same genes worked differently in the two species," says Liron Carmel, a member of the team that delved into genetic regulation in proto-humans for the first time.

My brother, the ape

With a nod to statistical probabilities, the human genome has been sequenced, and so have genomes of Neanderthals and Denisovans, with a high degree of accuracy. We can compare these genomes to see what genes we have in common, which turns out to be some 99%. We can see where mutations occurred that distinguish us from our sister species.

It bears mention in this context that the human genome and the chimpanzee genome, which was sequenced in 2005, differ by only 4%; the last common ancestor to chimp and Wimp lived five to seven million years ago. Humans split with Neanderthals and Denisovans between 550,000 to 765,000 years ago.

What we cannot see in genetic analyses is how the genes are expressed, if at all.

Yet the fact that our genomes are so very alike, while the end physical result is so very different, gave rise to the thought that perhaps the difference lay in genetic expression, not in the genes per se.

Everything from the lowest bacterium to the next-door neighbor has genes that are never expressed at all, genes that get expressed at specific times, and so on. Just think for instance about the genes that governed the development of your eyeball: you don't need those after your eye is "ready." Genes get "switched on" and "switched off" by regulatory biochemicals that stick to the DNA. Think of them as "off" and "on" keys, or keys that say, "Express this gene a lot."

"Epigenetics deals with heritable traits that are not caused by mutations, and are therefore not inheritable," says Carmel. The "epigenome" is the list of biochemicals that adhere to DNA in order to regulate its expression. And this is where the difference between you and a caveman seems to lie.

Reconstructing the primitive epigenome using rotting DNA

In an article in Science, Dr. Liran Carmel, Prof. Eran Meshorer and David Gokhman of the Institute of Life Sciences at the Hebrew University, with scientists from Germany and Spain, reconstructed the epigenome (a "picture" of which genes were pon and off) of the Neanderthal and the Denisovan for the first time.

Then they compared these dead species' epigenomes with that of modern humans. The scientists identified genes that existed in all three, but whose activity in humans was different.

They found major differences in the patterns of gene expression governing the development of the brain and skull, as well as in the immune and cardiovascular systems.

They didn't find much change regarding the genes that govern the digestive system, by the way.

The nucleic acid that shouldn't be there

How did they do it, you wonder. Comparing genes, fine – but their regulation? How can they tell if a gene in a 50,000-year old body (let's say) had been on or off?

Bizarrely enough, the solution lay in the fact that the Neanderthal and Denosivan DNA had been partly decomposed, Carmel explains.

To simplify, DNA consists of extremely long chains of nucleic acids. There are four types of nucleic acids, usually referred to simply as T, G, A and C.

Never mind why, but as DNA decomposes, the acid known as C gets turned into either T if the gene is "on," or U if the gene is "off." Or vice versa. It doesn't matter if it's on or off, just that we can tell the difference.

U stands for uracil and it has no business being in DNA. If it's there, therefore, it replaced a C nucleic acid molecule in a dead body. The scientists re-replace all the U molecules with C's (on the computer, not in the corpse) and calculate the ratios of C's and T's; thereby they can tell if an ancient gene had been on or off.

Their conclusion: our genes were much the same, but they were used in different ways.

On the downside, say the scientists, genes whose activity is unique to modern humans but not with the proto-humans include ones associated with Alzheimer’s disease, autism and schizophrenia, which are fairly common disorders today. On the upside, we're smarter.

Does this Neanderthal skull look very familiar? It should: You share 99% of this proto-human's genes. Credit: Anagoria, Wikimedia Commons
From left to right: Prof. Eran Meshorer, Dr. Liran Carmel, David Gokhman.Credit: Hebrew University of Jerusalem

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