A Chance Event 1 Million Years Ago Changed Human Brains Forever

There are certain DNA areas that evolution just won't dare change, much like cherished family recipes that are passed down from generation to generation. For instance, a variety of these encoded sequences that haven't changed in millions of years are shared by mammals from all over the world.

Strangely, humans are an exception to this rule. For whatever reason, during a short period of evolutionary time, long-preserved recipes from our prehistoric predecessors were abruptly "spiced up."

These areas are known as "human accelerated regions" (or HARs) since they have been rapidly rewritten in just our species. Additionally, many of the traits that distinguish humans from their close cousins, such as chimpanzees and bonobos, are thought to be caused by at least some HARs, according to experts.

The Gladstone Institute of Data Science and Biotechnology in the US is directed by computational biologist Katie Pollard. Nearly two decades ago, a research team examining the genomes of humans and chimpanzees discovered HARs.

In a recent study, Pollard's team discovered that this critical period for our species is significantly influenced by the 3D folding of human DNA in the nucleus.

Consider a segment of DNA from our last common ancestor with chimpanzees as a long scarf that is worn around the neck. The weave of the scarf has different-colored stripes that run the length of it.

Imagine that someone attempted to create the identical scarf but did not exactly adhere to the original pattern. The stripes vary in width, color sequence, and width and width. Some stripes are broader than others.

The stripes that previously sat next to one another in the loop of the scarf are no longer identical when you wrap it around your neck in the same manner as the first one.

Similar to this scarf, a significant structural difference between human and chimpanzee DNA is the presence of large insertions, deletions, and rearrangements in the human genome. Consequently, as compared to the DNA of other primates, human DNA folds differently in the nucleus.

Pollard's team looked into the possibility that certain genes inside HARs may have been "hijacked" and linked to other protein-coding genes than they were originally intended to by these structural alterations in human DNA and its changed 3D folding.

Numerous genes in HARs are connected to other genes and function as enhancers, which means they boost the transcription of the gene or genes to which they are related.

According to Pollard, "enhancers can affect any gene that ends up nearby, and this can vary depending on how DNA is folded."

The fast changes in HARs that emerged in early humans frequently contradicted one another, changing the activity of an enhancer up and down in a manner similar to genetic fine-tuning, according to a model developed by Pollard's team and validated by their latest findings.

In their most recent work, the group used machine learning to deal with a significant quantity of data as they compared the genomes of 241 mammal species.

The 3D 'neighborhoods' of folded DNA's 312 HARs were determined, and their locations were investigated. Nearly 30% of HARs were located in areas of the genome where structural differences have led the human genome to fold differently from those of other primates.

The study also found that HARs were located in areas that were abundant in the genes that set humans apart from our nearest living cousins, chimps.

One-third of the discovered HARs were specifically transcribed during the formation of the human neocortex, according to a study that analyzed the DNA of developing human and chimpanzee stem cells.

Numerous HARs are involved in the formation of brain connections that are connected to human qualities including intellect, reading comprehension, social skills, memory, attention, and focus in the embryo.

These enhancer genes in HARs may have needed to adapt to their many target genes and regulatory domains while having remained unaltered for millions of years.

"Imagine you're an enhancer controlling blood hormone levels, and then the DNA folds in a new way and suddenly, you're sitting next to a neurotransmitter gene and need to regulate chemical levels in the brain instead of the blood," Pollard said.

"Our cells have to act quickly to fix a problem when something big happens, like this significant change in genome folding, to prevent an evolutionary disadvantage."

We still don't fully comprehend how these modifications affected particular features of human brain growth and how they were incorporated into the DNA of our species. Pollard and her colleagues are already preparing to explore these issues, though.

However, their first findings clearly highlight how singular - and improbable - the evolution of the human brain is.

This study was published in Science.