Jacob Michaelson, PhD, Roy J. Carver Professor of Psychiatry and Neuroscience at the UI Roy J. and Lucille A. Carver College of Medicine, says language is one of the defining characteristics of Homo sapiens. Many animals communicate, but humans possess an exceptional ability to create, adapt, and expand language in ways unmatched by other species.

Michaelson and his colleagues, including first author Lucas Casten, PhD, now a postdoctoral researcher at the Max Planck Institute of Psychiatry in Munich, Germany, set out to investigate how human language development may have been influenced by genetic regulatory elements known as Human Ancestor Quickly Evolved Regions (HAQERs).

"What we're seeing is how a very small part of the genome can have an outsized influence, not just on who we were as a species, but on who we are as individuals," Michaelson says, noting that HAQERs represent less than a tenth of a percent of the genome but drive roughly 200 times more impact on language ability than any other genomic region.

According to the researchers, these DNA regions help build the brain's biological "hardware," while language itself functions as the "software."

Ancient DNA and the Origins of Language

The findings, published in Science Advances, build on research that began in the 1990s. At that time, Bruce Tomblin, PhD, now professor emeritus in the UI Department of Communication Sciences and Disorders, studied the language abilities of 350 students in Iowa.

Tomblin carefully documented each student's language skills and collected saliva samples, preserving DNA that could be analyzed in the future. Years later, Michaelson's laboratory completed genetic sequencing through NIH-funded research, making it possible to examine how differences in DNA related to variations in language ability.

As researchers explored the data, they became interested in the broader role of HAQERs in human communication.

"These aren't genes we're talking about. They're regulatory regions that act like the volume knob on genes," Michaelson explains, adding that the findings quickly connected with a seminal study from over 20 years ago that identified the FOXP2 gene, a transcription factor, which was initially suspected as playing a major role in language impairment. "So, if the HAQERs are like volume knobs that can be turned, FOXP2 is one of the hands that is turning these volume knobs."

To better measure HAQERs' influence, the researchers created an evolutionary-stratified polygenic score (ES-PGS), a tool that separates genetic effects according to when they emerged during evolution. Using computational genetics, the team traced genetic influences across approximately 65 million years of evolutionary history.

Shared Genetic Features With Neanderthals

The analysis revealed that these genetic "volume knobs" were already present in Neanderthals and may have been even slightly more pronounced than they are in modern humans.

For the researchers, this was an especially significant finding because it suggests that HAQERs are ancient biological innovations linked to language. That connection exists despite the likelihood that Neanderthals differed substantially from modern humans in many aspects of cognition.

"This HAQERs aspect, a sliver of the genome, has remained relatively constant, even as other aspects have been going up and up and up to make modern humans smarter and smarter," Michaelson says. "We can say humans at least had the 'hardware' for language earlier than what we previously thought."

Michaelson notes that archaeological evidence already shows Neanderthals had culture, social organization, and complex behaviors. When combined with the new genetic findings, those observations strongly suggest that some form of sophisticated communication may have existed long before modern humans appeared.

The results also raise an important question. If HAQERs are so beneficial for language, why did they stop changing rather than continuing to evolve?

An Evolutionary Tradeoff

The researchers believe the answer involves a process known as balancing selection.

While genetic signals associated with other cognitive abilities continued to evolve, the influence of HAQERs appears to have reached a plateau. According to the team, these genetic regions support fetal brain development in ways that also increase brain and skull size.

Before modern medicine, however, there were limits to how large an infant's head could become before childbirth became dangerously difficult for both mother and child. Larger head size could significantly increase mortality risks during delivery.

"We think that early humans maxed out this pathway to developing the kind of brain that could be a vessel for language and they hit that ceiling pretty early on and then remained stable, while other aspects of genetics that improve brain development for higher intelligence but don't directly affect fetal brain size, continued to evolve," Michaelson says.

In other words, human evolution may have reached a point where further improvements to the biological "hardware" supporting language would have come at too great a cost to maternal and infant survival.

Separating Genetics From Environment

The team plans to continue exploring these questions using the same group of participants originally studied by Tomblin.

Because that research began about three decades ago, many of those participants now have children and families of their own. This creates a valuable opportunity to investigate how language ability is shaped by both inherited genetics and environmental influences.

"One of the things we're interested in is disentangling the environmental input from the genetic input, when thinking about how a child masters language," Michaelson says, noting that children raised in a linguistically rich environment may present with higher language capabilities. "Using that family structure, we hope to separate the direct genetic effects on language and what researchers call 'genetic nurture' where the parents' genetics influence the environment they create for their kids."

Michaelson says the University of Iowa has advanced statistical tools that may help researchers distinguish the environmental contribution to language learning from genetic influences. Such insights could have important clinical applications.

To pursue that work, Michaelson and Kristi Hendrickson, PhD, associate professor of communication sciences and disorders, have submitted a grant proposal to support the next phase of the research.

In addition to Michaelson, Casten, and Tomblin, the research team included current and former UI researchers Dabney Hofammann, Savantha Thenuwara, Allison Momany, Marlea O'Brien, Jeffery C. Murray, and Tanner Koomar (now with Recursion Pharmaceuticals). Taylor R. Thomas of the Center for Genomic Research at Massachusetts General Hospital and Jin-Young Koh of the University of Maryland also contributed to the study.

The research was funded in part by grants from the National Institute on Deafness and Other Communication Disorders and the National Institute of General Medical Sciences, both part of the National Institutes of Health, as well as the Roy J. Carver Charitable Trust.