Humans may have had a competitive edge over our ancient relatives, study suggests

By Mindy Weisberger, CNN

(CNN) — Modern humans are evolutionary survivors, thriving generation after generation while our ancient relatives died out. Now, new research into our brain chemistry suggests that an enzyme unique to Homo sapiens may have made us more efficient water seekers than our closest extinct relatives.

About 600,000 years ago, modern humans genetically diverged from the lineage that produced Neanderthals and Denisovans — our closest cousins in the family tree of human species. At some point after the split, an enzyme called adenylosuccinate lyase, or ADSL, evolved to be different in Homo sapiens. In the enzyme’s chain of 484 amino acids, one amino acid at position 429, called alanine, was replaced with valine. It’s a small change, but it produced a version of ADSL that only modern humans possess.

The enzyme is a key component in producing purine, a building block of DNA and RNA. When ADSL is absent in modern humans, it can lead to behavioral abnormalities such as hyperactivity and aggressiveness. Scientists investigated how our behavior might be shaped by that change in a single amino acid. Their research was published August 4 in the journal PNAS.

“Uncovering how tiny genetic changes from our ancient past helped shape brain traits that make us human is exciting,” said lead study author Dr. Xiang-Chun Ju, a postdoctoral scholar in the Human Evolutionary Genomics Unit at Japan’s Okinawa Institute of Science and Technology.

“Studying our ancient origins is like assembling a giant puzzle, where each genetic change in our ancestors may offer a clue to how our brains and behaviors evolved,” Ju told CNN in an email.

An affinity for water

Earlier research showed that the ADSL variation in modern humans makes the enzyme less stable and less effective in its production of purine. By comparison, the original version of ADSL, carried by Neanderthals and Denisovans, is more efficient at synthesizing certain protein molecules. In Homo sapiens, these molecules accumulate in organs — especially the brain.

To learn how this could affect behavior, researchers conducted experiments with mice; some were genetically modified to carry the less-efficient version of ADSL, mimicking human ADSL. They tested these “humanized” mice, along with a control group of unaltered mice, by first gradually restricting their access to water over 12 days, and then making water available, signaled by the presence of sound and light. The scientists found that female mice with the human variant of the enzyme visited the water dispensing area more frequently when they were thirsty.

Perhaps, the scientists hypothesized, this less-efficient version of ADSL had a positive impact on accessing water, increasing Homo sapiens’ competitiveness for this vital resource.

In a second line of investigation, researchers looked at the modern human genome, focusing on the ADSL gene that produces our unique version of the enzyme. They found a cluster of genetic variants carried by at least 97% of present-day humans, which make ADSL even less efficient at expressing RNA, potentially amplifying its impact on behavior. The gene’s location was in a region of the genome that was evolutionarily favored in humans, hinting that this change in ADSL expression kept being passed along because it likely provided humans with some advantage, the study authors reported.

“It is really exciting that through such studies, we are moving beyond identifying the genetic changes that make modern humans unique, towards understanding how these changes may have shaped our uniqueness,” said Dr. ​​Maanasa Raghavan, an assistant professor of human genetics at the University of Chicago, who was not involved in the research.

“This study raises intriguing possibilities about how our ancestors might have gained an advantage over contemporaries like Neanderthals and Denisovans in unstable environments with limited resources,” Raghavan said in an email.

Modern humans: The last surviving hominin species

The first complete genome of a Neanderthal was sequenced in 2010, and scientists sequenced the first Denisovan genome two years later. By comparing their genetic data with that of modern humans spanning Africa, Asia and Europe, scientists are identifying behaviors that may have helped modern humans succeed while other hominin species died out, the researchers reported.

“It adds to the picture that many of the changes that happened in modern humans affect how our brains develop and function,” Ju said. “It is a step towards understanding these changes and eventually how they may work together.”

Of course, humans are not mice, and the new findings alone cannot directly explain human behavior, said Dr. Ingrida Domarkienė, a senior researcher in the department of human and medical genetics at Vilnius University in Lithuania. In addition to ADSL, roughly 80 amino acid variants exist between Homo sapiens and Neanderthals, she added.

“However, this doesn’t necessarily mean that these changes alone defined who we are,” Domarkienė, who studies ancient DNA but was not involved in the research, told CNN in an email. Rather, variations in our amino acids may have created opportunities that combined with other conditions — such as environment, intelligence, disease resistance and social structure — to shape our evolutionary success and leave modern humans as the last surviving hominin species.

“I believe that the ‘loneliness’ of modern humans, in terms of being the only surviving lineage, was determined by a complex set of factors — and to some extent, chance,” Domarkienė said. “The results of this study bring us closer to understanding how we got here.”

The findings raise other intriguing questions about the link between ADSL and behavior, according to Ju. Scientists are still unsure about how the precise molecular and cellular mechanisms of ADSL shape its influence on the human brain, and it is unknown why experimental changes to ADSL affected the behaviors of only female mice.

“Could other behaviors, not examined in this study, also be influenced by this amino acid change?” Ju asked. “Most importantly, what might be the functional consequences in humans? Those are questions that we and others will now try to address.”

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