What are human accelerated regions?

Let's see what is so special about the genome segments known as human accelerated regions.

Human Accelerated Regions (HARs) are a set of segments of the human genome that, although shared with other vertebrates, are observed in a markedly different way in vertebrates. which, despite being shared with other vertebrates, are observed in a markedly different way in our species.

What differentiates us from a chimpanzee? The behaviors, cognitive expressions and capacity to generate languages and civilizations are a reflection of the neurological development of human beings at two different levels: one genetic and the other cultural. Thus, to unravel the secrets of these characteristics that make us so different from other animal species, it is necessary to turn to our evolutionary history and genetic mapping.

Human accelerated regions, or HARs, attempt to answer this impressive question, as the variation in locus (fixed positions on a chromosome) between similar species, such as humans and chimpanzees, may in part be the answer to the evolutionary engine that has brought us to a "dominant" position as a species on Earth.

Human accelerated regions: the key to behavior.

Comparative genomics studies the similarities and differences between the similarities and differences between the set of genes in the chromosomes of the planet's organisms..

This scientific discipline seeks to discover which characteristics have been fixed by natural selection over time, in order to understand the different evolutionary pressures to which living beings have been subjected over the course of their generations.

To understand these underlying mechanisms that push living beings to vary over time, it is necessary to clarify that there is a phenomenon of "genetic purification" in the natural world.In addition, it is necessary to clarify that there is a phenomenon of "genetic purification" in the natural world.

What happens when we deviate from natural selection?

It should be noted that negative selection is an evolutionary mechanism by which deleterious alleles (each of the two or more versions of a gene) for a species are eliminated over time, "purifying" the gene pool of the population.

For example, an animal with a mutation that is not beneficial to the community it inhabits will have fewer offspring or die out faster (population genetics mechanisms), which will eliminate that deleterious allele over generations. If a bird is born without an eye due to a mutation, you would expect it to reproduce less or be hunted faster than the rest, right?

But... what about humans? that we have gotten rid of this mechanism of negative selection, because in a world from a western point of view, the survival rate of the individual is not influenced by his mutational impediments, as long as medicine allows it (autoimmune diseases or lack of a limb, for example). This, among many other factors resulting from a purely anthropic society, could lead to three mechanisms:

• Accumulation of neutral mutations in gene sequences that have lost their essential function.
• Biased gene conversion by not responding to adaptive evolution.
• Change of a negative selection influence by a positive selection mechanism.

We are moving in a very difficult terrain that includes very complex genetic terminology, but one idea must be clear: human accelerated regions undergo relatively rapid mutation rates. compared to the rest of the genome, and due to a lack of selective pressure and adaptive responses, these areas are highly divergent compared to other hominids.

Coding and conclusive, or not?

At this point, it is essential to emphasize that 99 % of human DNA is non-codingthat is to say, it does not contain information for the production of proteins, and therefore does not act directly on the individual's metabolism.

Although these DNA segments were initially thought to be "junk", it is increasingly recognized that they play essential roles in regulating the activation of essential genes in various ways, as it has been shown that certain regions can promote the activation or repression of the transcription of certain proteins.

This is one of the major problems of human accelerated regions, as 92% of them are in non-coding regions. Therefore, most of these genetic elements are in uncharacterized areas of the genome and their evolutionary conservation does not necessarily predict a specific differential function in humans.

Even so, this does not mean that these highly mutated areas of the genome are uncharacterized, this does not mean that these highly mutated areas do not respond to human characteristics.. Many of them are present in "intergenic" regions, i.e., regulatory sequences that could modulate the expression or suppression of certain coding genes. Of course, these ideas need to be studied further to reach firm conclusions.

A practical example

To understand this whole mutagenic and evolutionary conglomerate, the best way is to use an example. We have before us the HAR1 region, a DNA sequence composed of 118 nucleotides; commonly referred to as bases, after the nitrogenous base that each of them contains, adenine, cytosine, thymine and guanine. Let's look at some revealing facts about this segment:

• When we compare the HAR1 region between humans and chimpanzees we see that there are 18 different bases.
• If we compare the same region between a chicken and a chimpanzee, we only find a difference of two bases.
• The chimpanzee lineage diverged from humans 6 million years ago, while chickens diverged from them 300 million years ago.
• This sequence is not present in fish and frogs.

This data must mean something, right? Otherwise, what sense does it make that more variation is present between two lineages that diverged relatively recently? This fact raises the suspicion that this rapid rate of mutation may be correlated with some of the characteristics that make us define ourselves as "human".

To make things more interesting, other studies have demonstrated that the five fastest mutating human accelerated regions have 26 times more substitutions (mutations) than their analogs in chimpanzees..

But are there differences between HARs in human evolutionary history? According to other sources, the differences in these regions between archaic hominins (Neanderthals) and modern humans is about 8%, which exemplifies that this evolutionary divergence that characterizes us must have accelerated about 500,000 years ago, and could have been decisive for the characterization of the genus Homo. Of course, variations in the human genome throughout our evolutionary history may hold much of the answer to our characteristics as a species.

HARs and mental disorders

Even more surprisingly, studies have found that certain mutated genes are found in the vicinity of the that certain mutated genes are found in the vicinity of these accelerated regions in patients with mental disorders such as schizophrenia such as schizophrenia, and therefore it is postulated that they could be influenced by them.

Beyond this, other research has documented that several genetic variations in patients with autism are found in accelerated regions. This could translate into a specific modulation when it comes to the production of proteins that interact with the brain, which would condition a "normal" functioning in the individual's behavior.

Conclusions

As we have seen, the human accelerated regions are segments of DNA that could play an essential role in the development of human beings, i.e. those special characteristics that define us as a species.that is to say, those special characteristics that define us as a species.

In addition, studies have revealed that they could modulate the expression of certain genes, which would condition the individual's metabolism and therefore his or her behavior, especially in disorders such as schizophrenia or autism.

Although the research has laid a promising foundation, it is essential to emphasize that at no time have we ceased to move within theoretical and experimental frameworks. None of the above should be interpreted as dogma or absolute reality, as a long period of research is still required to understand the uniqueness of these gene segments.

Bibliographical references:

• Allele, National Genome Human Research Institute. Recogido a 31 de agosto en https://www.genome.gov/es/genetics-glossary/Alelo
• Capra, J. A., Erwin, G. D., McKinsey, G., Rubenstein, J. L., & Pollard, K. S. (2013). Many human accelerated regions are developmental enhancers. Philosophical Transactions of the Royal Society B: Biological Sciences, 368(1632), 20130025.
• Doan, R. N., Bae, B. I., Cubelos, B., Chang, C., Hossain, A. A., Al-Saad, S., ... & Gascon, G. G. (2016). Mutations in human accelerated regions disrupt cognition and social behavior. Cell, 167(2), 341-354.
• Hubisz, M. J., & Pollard, K. S. (2014). Exploring the genesis and functions of Human Accelerated Regions sheds light on their role in human evolution. Current opinion in genetics & development, 29, 15-21.
• Katzman, S., Kern, A. D., Pollard, K. S., Salama, S. R., & Haussler, D. (2010). GC-biased evolution near human accelerated regions. PLoS Genet, 6(5), e1000960.
• Levchenko, A., Kanapin, A., Samsonova, A., & Gainetdinov, R. R. (2018). Human accelerated regions and other human-specific sequence variations in the context of evolution and their relevance for brain development. Genome biology and evolution, 10(1), 166-188.
• What is non-coding DNA. Genetics Home Reference. Recogido a 31 de agosto en https://ghr.nlm.nih.gov/primer/basics/noncodingdna