Typically Human: Scientists have identified genomic regions that may account for our uniquely human adaptations. The sections of DNA called HAQERs (Human Ancestor Quickly Evolved Regions) control the reading of protein-coding genes and thus contribute to the development of our brain, digestive tract and immune system. They evolved shortly after the human and chimpanzee lineages separated. HAQERS not only bring benefits, but also diseases.
We humans distinguish ourselves from our closest primate relatives like chimpanzees or gorillas. But the genetic causes of our “typically human” characteristics are only just beginning in pieces clarified – also because there are hardly any differences in the protein-coding genes to the great apes. On the other hand, there is increasing evidence that the decisive changes took place in the non-protein-coding parts of our genome – the part that was long considered non-functional “junk DNA“ applied.
Rapid change
A team led by Riley Mangan from Duke University in the USA has now also searched for traces of our evolution in these non-coding sections of our genome. So far, the DNA sequences that have remained stable for a long time, but then changed quickly in our ancestors, have been considered particularly promising. “It was assumed that such an acceleration of molecular evolution reflects a change in selection,” the researchers explain.
In contrast, Mangan and his colleagues have now also searched the regions of the genome that had already undergone dynamic changes. “Many unique features of human anatomy, including brain size, limb proportions, or facial anatomy, were not static even in non-human species,” they explain. Using high-throughput sequencing and genome comparisons, they searched for the DNA segments in these genome regions that changed particularly rapidly after the chimpanzee and human lineages split around 7.5 million years ago.
HAQER in our genome
In fact, the researchers managed to identify over 1,500 such sections. They dubbed them HAQERs (pronounced “Hackers”), which stands for Human Ancestor Quickly Evolved Regions. As they report, these DNA sections are among the most rapidly developed in the human genome. But when did this enormous development push take place? In the course of pre- or early human evolution? Or already when splitting off from the chimpanzee?
To check this, Mangan and his colleagues synthesized the 13 most meaningful sequences of their HAQERs sections and compared them with the genome of Neanderthals, Denisova peoplechimpanzees and the reconstructed genome of the putative common ancestor of humans and chimpanzees.
The result: The HAQERs evolved after our family line split from that of the chimpanzee, but before we in turn split from the Denisovans and the Neanderthals. This means that other pre-human and early human species also had these sequences.
Fine-tuning for the brain and gut
But what is the function of the HAQER sequences? The scientists characterize them as regulatory sections of DNA that work like a kind of switch. “They seem to turn on genes very specifically. They only do this in certain cell types and only at certain times of development. Or even only if the environment changes in some way,” explains Mangan’s colleague Craig Lowe. The HAQERs added some gene switches to the human operating system that hadn’t existed before.
As detailed analyzes revealed, these gene switches are primarily used in the development of the human brain, the gastrointestinal tract and parts of the immune system. The gene switches allow us a special fine-tuning, with which we can specifically adapt to changing environmental influences.
HAQERs as triggers of typical human diseases
But how did the HAQERs come about? Normally, there are two common explanations for the rapid emergence of genomic regions: either they come about as a result of local mutations, or they turn out to be so advantageous for a species that they prevail in the course of natural selection. In the DNA sequences that have now been characterized, the scientists found evidence for both explanations, “suggesting that the combination of these two forces has shaped the most divergent regions in the human genome.”
By making us human, the HAQERs not only gave us positive characteristics such as large brains, but also created the basis for typical human diseases, as the researchers suspect. These could include high blood pressure, unipolar and bipolar depression, and schizophrenia.
According to Mangan and colleagues, although all humans have very similar HAQER sequences, there are some variations, “and we were able to show that these variants tend to correlate with certain diseases,” says Lowe. Exactly what this connection looks like could be the goal of further research. (Cell, 2022; doi: 10.1016/j.cell.2022.10.016)
Source: Duke University