In a first-of-its-kind finding, researchers at University of Iowa Health Care discovered that specific genetic sequences have an outsized impact on humans' language abilities and that these sequences evolved before humans and Neanderthals diverged.
The study's senior author Jacob Michaelson, PhD, Roy J. Carver Professor of Psychiatry and Neuroscience with the UI Roy J. and Lucille A. Carver College of Medicine, describes language as a defining trait of Homo sapiens. While other animals communicate in various ways, humans' propensity for developing and improvising language is unique to earth's dominant species. The research, conducted by Michaelson's team, including first author Lucas Casten, PhD, now a postdoctoral researcher at the Max Planck Institute of Psychiatry in Munich, Germany, aims to understand how the development of human language was shaped by genetic regulatory sequences 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.
These parts of the genome serve as instructions for building the "hardware" of the brain, while language represents the "software."
Ancient genetic innovations
The new study, published April 22 in Science Advances, has its foundation in work done in the 1990s by Bruce Tomblin, PhD, now professor emeritus of the UI Department of Communication Sciences and Disorders. Tomblin studied a cohort of 350 Iowa students to better understand their language abilities. Tomblin meticulously documented the students' language abilities, and he also collected saliva, preserving their DNA for future gene sequencing. That process was completed by Michaelson's lab in NIH-funded research, allowing the researchers to look at the differences in DNA and how gene variations affected the student's language skills.
Through that analysis, they started examining the broader impact of HAQERs on a person's ability to communicate using language.
"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 further understand the impact of HAQERs, the team developed an evolutionary-stratified polygenic score (ES-PGS) that partitioned genetic effects based on their evolutionary origins. Using computational genetics, the team examined 65 million years of evolutionary history.
As it turns out, these "volume knobs" were present in Neanderthals and may have even been a bit more prominent than they are in us today. This finding was striking to the team as it reveals how HAQERS are ancient innovations that shape language, even though the overall cognitive abilities of Neanderthals were likely far different than modern day humans.
"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 adds that when layered with the archaeological evidence that Neanderthals had culture and organized social structures, it's heavily implied that some form of complex communication existed.
But it also begs the question that if HAQERs are so beneficial for language, why did they remain constant rather than continue to evolve into new gene variants?
An evolutionary tradeoff
The answer lies in the phenomenon known as balancing selection. In this case, HAQERs' genetic signal plateaued while other signals for cognitive abilities continue to change as modern humans evolved. According to Michaelson's team, HAQERs promote fetal brain development in ways that also increase the size of the brain and therefore the skull. Prior to modern medicine, there was a clear ceiling for how big a baby's head could get before delivery became catastrophically dangerous for both mother and child, increasing mortality for both.
"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.
Essentially, humans underwent an evolutionary tradeoff where the "hardware" for language couldn't be optimized any further through HAQERs without increased mortality among mothers and infants.
Disentangling environmental factors from genetics
Michaelson's lab looks to further this research with additional studies involving the cohort of children analyzed by Tomblin. Because that original investigation occurred roughly 30 years ago, those participants now have families of their own, offering an expanded sample for genetic research.
"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 notes that the UI has access to sophisticated, statistical tools that will help parse out the part of a child's language learning ability that is purely environmental, something that would be valuable from a clinical perspective.
Michaelson has submitted a grant with Kristi Hendrickson, PhD, associate professor of communication sciences and disorders, to complete this study.
In addition to Michaelson, Casten, and Tomblin, the 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 were also part of the team.
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, and the Roy J. Carver Charitable Trust.
