What are human accelerated regions?

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

What makes us different from a chimpanzee? Behaviors, cognitive expressions and the ability to generate languages ​​and civilizations are a reflection of the neurological development of the human being 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 go to our evolutionary history and genetic mapping.

Human accelerated regions or HARs try to answer this impressive question, since the variation in loci (fixed positions of a chromosome) between species similarities, such as humans and chimpanzees, could be partly the response to the evolutionary engine that has led us to a "dominant" position as a species in the Land.

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Human Accelerated Regions: The Key to Behavior

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

This scientific discipline tries to discover what characteristics have been fixed by natural selection throughout the time, in order to understand the different evolutionary pressures to which living beings have been subjected throughout their lives. generations.

To understand these underlying mechanisms that push living things to vary over time, 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 is necessary to note that negative selection is an evolutionary mechanism by which alleles deleterious (each of 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 that presents a mutation that is not beneficial to the community in which it lives will have fewer descendants or will die faster (population genetics mechanisms), which will eliminate that deleterious allele throughout the generations. 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 got 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 its mutational impediments, as long as medicine allows it (autoimmune diseases or missing limbs, for example). 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.
• Exchange of a negative selection influence for a positive selection mechanism.

We move in tricky terrain that includes very complex genetic terminology, but one idea must be clear: human accelerated regions suffer relatively fast mutation rates Compared to the rest of the genome, and due to a lack of selective pressure and adaptive responses, these zones are highly divergent compared to other hominins.

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Codifying and conclusive, or not?

In this point, it is essential to emphasize that 99% of human DNA is non-coding, that is, it does not present information for the production of proteins, and therefore does not act directly on the metabolism of the individual.

Although at first it was thought that these DNA segments were "junk", it is increasingly recognized that they play essential roles in the regulation of 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 great problems of human accelerated regions, since 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 need not predict a specific differential function in living beings. humans.

Even so, this does not mean that these highly mutated areas do not respond to human characteristics. Many of them are present in "intergenic" regions, that is, regulatory sequences that could modulate the expression or suppression of certain genes that are codified. Of course, these ideas must be studied in more depth to reach reliable conclusions.

A practical example

To understand all this mutagenic and evolutionary conglomerate, it is best that we turn to an example. We have before us the HAR1 region, a DNA sequence made up of 118 nucleotides; commonly called bases, due to 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 the same region is compared 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 humans 300 million years ago.
• This sequence is not present in fish and frogs.

These data have to mean something, right? Otherwise, what's the point of more variation occurring between two lineages that have differentiated relatively recently? This fact makes us suspect that this fast rate of mutation may be correlated with some characteristics that make us define ourselves as "humans".

To make matters more interesting, other studies have shown that the five fastest-mutating human accelerated regions have 26 times more substitutions (mutations) than their chimpanzee counterparts.

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 around 8%, which exemplifies that this evolutionary divergence that characterizes us must have accelerated around 500,000 years ago, and could have been decisive for the characterization of the genus Homo. Of course, the variations in the human genome throughout our evolutionary history may contain much of the answer to our characteristics as a species.

HARs and mental disorders

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

Beyond this, other research has documented that various genetic variations in autism patients 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, that is, those very 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 metabolism of the individual and therefore his behavior, especially in disorders such as schizophrenia or autism.

As much as the research has laid some promising foundations, it is essential to underline that at no time have we stopped moving in theoretical and experimental frameworks. None of what is stated here must be interpreted as a dogma or an absolute reality, since it is still requires an extensive period of research to understand the uniqueness of these segments genetic.

Bibliographic references:

• Allele, National Genome Human Research Institute. Collected on August 31 in 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. Collected on August 31 in https://ghr.nlm.nih.gov/primer/basics/noncodingdna