Genetic study emphasizes the significance of “balancing selection” in evolution

Nature can maintain various genetic features in balance as a species grows over millions of years, much like a merchant of old would do when balancing the weights of two distinct products on a scale.

Depending on the environment, these features could be advantageous (for example, warding off sickness) or detrimental (making people more prone to illness).

Balancing selection is the concept behind these trade-offs in evolutionary processes. Research headed by the University at Buffalo examines this phenomenon by comparing the genomes of thousands of modern humans with those of extinct hominin populations like the Neanderthal and Denisovan. The study was approved on January 10^th, 2023 and released on February 21^st, 2023 in the journal eLife.

The research has implications for understanding human diversity, the origin of diseases, and biological trade-offs that may have shaped our evolution.”

Omer Gokcumen, PhD, Study Corresponding Author and Associate Professor, Biological Sciences, College of Arts and Sciences, University at Buffalo

He added, “The study shows that many biologically relevant variants have been segregating among our ancestors for hundreds of thousands, or even millions, of years. These ancient variations are our shared legacy as a species.”

Ties with Neanderthals stronger than previously thought

The research relies on genetic discoveries made during the previous ten years, such as the discovery that Neanderthals and modern humans interbred as early humans left Africa.

Personalized genetic testing is also expanding at the same time, and many people now assert that a small portion of their DNA is derived from Neanderthals. But, as the eLife study demonstrated, humans and Neanderthals have considerably more in common than those negligible percentages suggest.

This additional sharing can be linked to a Neanderthal ancestor that lived around 700,000 years ago, together with humans. The genetic variety that the Neanderthals and modern humans share is a legacy left by their common ancestors.

The study group investigated this ancient genetic legacy, focusing on a particular form of genetic variation: deletions.

Gokcumen further stated, “Deletions are strange because they affect large segments. Some of us are missing large chunks of our genome. These deletions should have negative effects and, as a result, be eliminated from the population by natural selection. However, we observed that some deletions are older than modern humans, dating back millions of years ago.”

Gene variations passed down over millions of years

A surplus of these ancient deletions, some of which have remained since human ancestors first learned to build tools, around 2.6 million years ago, was demonstrated by researchers using computational models. The models also discovered that balancing selection can account for this excess of ancient deletions.

Our study contributes to the growing body of evidence suggesting that balancing selection may be an important force in the evolution of genomic variation among humans.”

Alber Aqil, PhD Student, Biological Sciences, College of Arts and Sciences, University at Buffalo

The researchers discovered that deletions that have been present for millions of years are more likely to have a significant impact on autoimmune and metabolic diseases.

Scientists have long been perplexed by the longevity of genetic variations that cause severe disease in human populations since they had expected natural selection to eliminate these gene variations. After all, it is quite uncommon for potentially disease-causing variation to survive for this long. The authors contend that balancing selection is the key to unlocking this puzzle.

Aqil added, “These variations may protect against infectious diseases, outbreaks, and starvation, which have occurred periodically throughout human history. Thus, the findings represent a considerable leap in our understanding of how genetic variations evolve in humans. A variant may be protective against a pathogen or starvation while also underlying certain metabolic or autoimmune disorders, like Crohn’s disease.”