Like precious recipes passed down from generation to generation, there are sections of DNA that evolution dares not change.
For example, in mammals there are many such encoded sequences that have remained unchanged for millions of years. Humans are a strange exception.
Since we are the only species in which these regions are overwritten so quickly, they are called “Human Accelerated Regions” (or HARs). What’s more, scientists believe that at least some of the HARs may be responsible for many of the traits that distinguish humans from chimpanzees and bonobos.
Led by computational biologist Cathy Pollard, director of the Gladstone Institute for Data Science and Biotechnology in the US, a team of researchers identified HAR almost two decades ago by comparing human and chimpanzee genomes.
In a new study, Pollard’s team found that the three-dimensional folding of human DNA in the nucleus is a key factor at this turning point for our species.
Think of the DNA strand of our last common ancestor with the chimpanzee as a long scarf wrapped around your neck, with bands of different colors running through the weave along its length.
Now imagine that someone tried to make the exact same scarf, but didn’t exactly follow the original pattern. Some lines are narrower, some are wider, and some have colors in a different order than the original.
And when you wrap this new scarf around your neck the same way you wrapped the original scarf, the lines next to each other in the loop will no longer be the same.
Like this mantle, there is a big difference between human and chimpanzee DNA: large parts of the building blocks of DNA have been inserted, removed or rearranged in the human genome. Therefore, human DNA fits into the nucleus differently than monkey DNA.
Pollard’s team investigated whether these structural changes in human DNA and altered three-dimensional folding could lead to certain genes being “captured” in the HAR, splicing them to other protein-coding genes than those originally applied.
Many of the genes within the HAR are linked to other genes, acting as enhancers (meaning they increase the transcription of related genes/genes).
Enhancers can affect the activity of any gene that happens to be in close proximity, which can vary depending on how the DNA is folded.”
In a study published earlier this year, Pollard’s team created a model that suggests that the rapid changes seen in HAR in early humans often conflicted with each other, shifting enhancer activity up and down in a kind of genetic control. new research.
In the latest study, the team compared the genomes of 241 mammalian species using machine learning to process a large amount of data.
They identified 312 HARs and examined their location in the three-dimensional “neighbourhood” of folded DNA. Approximately 30% of the HARs were in regions of DNA where structural differences caused the genome to fold differently in humans compared to other primates.
The team also found that organisms with HAR were rich in genes that distinguish humans from chimpanzees.
And in an experiment that compared DNA inside growing human and chimpanzee stem cells, a third of the identified HARs were transcribed specifically during the development of the human neocortex.
Many HARs play a role in fetal development, especially in the formation of neural pathways associated with intelligence, reading, social skills, memory, attention, and concentration—features that we know are distinctly different in humans from other animals.
And in HAR, these boosted genes, which have not changed for millions of years, probably had to adapt to their different target genes and regulatory domains.
We do not yet understand exactly how these changes affected certain aspects of our brain development and how they became an integral part of the DNA of our species.
This study was published in Science.
Source: Science Alert