From Newsgroup: sci.lang
HAQERS & human language evolution
https://doi.org/10.1101/2025.03.07.641231
Ancient regulatory evolution shapes individual language abilities in present-day humans
Lucas G Casten, Tanner Koomar, Taylor R Thomas, Jin-Young Koh, Dabney Hofammann, Savantha Thenuwara, Allison Momany, Marlea OrCOBrien, Jeffrey C Murray, J Bruce Tomblin, Jacob J Michaelson
doi:
https://doi.org/10.1101/2025.03.07.641231
Abstract
Language is a defining feature of our species, yet the genomic changes enabling it remain poorly understood. Despite decades of work since FOXP2rCOs discovery, we still lack a clear picture of which regions shaped language evolution and how variation contributes to present-day phenotypic differences. Using a novel evolutionary stratified polygenic score approach in nearly 40,000 individuals, we find that Human Ancestor Quickly Evolved Regions (HAQERs) are specifically associated with language but not general cognition. HAQERs evolved before the humanrCoNeanderthal split, giving hominins stronger binding of Forkhead and Homeobox transcription factors, and show balancing selection across the past 20,000 years. Remarkably, language variants in HAQERs appear more prevalent in Neanderthals and have convergently evolved across vocal-learning mammals. Our results reveal how ancient innovations continue shaping human language.
INTRODUCTION Human language is one of our speciesrCO most defining features, yet its genetic foundations remain incompletely understood. Previous research has shown how rare mutations in genes like FOXP2 can cause severe speech and language disorders, but these individual genes cannot explain typical variation in language capabilities or the broader evolutionary emergence of human language. Recent work has focused on identifying common genetic variants associated with language-related traits through large-scale genome-wide association studies, which have revealed hundreds of genomic loci contributing to traits like reading ability, rhythm, stuttering and vocabulary development. This emerging picture supports a highly polygenic architecture for language abilities, with numerous regulatory elements scattered throughout the genome collectively influencing language development. However, this polygenic model has left fundamental evolutionary questions unanswered about how these regulatory elements evolved during human evolution and when our species acquired its unique language-promoting functions.
RESULTS Through analysis of nearly 40,000 individuals across multiple cohorts with detailed language phenotyping, we discovered that Human Ancestor Quickly Evolved Regions (HAQERs), genomic sequences that began rapidly accumulating mutations before the human-neanderthal ancestral split, show specific and robust associations with language abilities but not with nonverbal IQ. A single nucleotide polymorphism in a HAQER carries on average 188 times more impact on language ability than variants elsewhere in the genome, despite HAQERs comprising less than 0.1% of the human genome. We find that HAQERs evolved in hominins to support language through increased binding affinity to Forkhead and Homeobox box transcription factors, including FOXP2, with these binding motifs linked to individual differences in language capability. Additionally, HAQERs provided humans with novel cell-type-specific chromatin accessibility, including in medium spiny neurons and FOXP2 -expressing neurons. Ancient DNA analysis of early humans from the past 20,000 years revealed that language-promoting HAQER variants have remained stable in frequency, likely due to balancing selection, contrasting with general cognition variants that show evidence of recent positive selection. This apparent balancing selection can be explained by the link between HAQERs and prenatal development, including a larger head size at birth and birth complications. Surprisingly, archaic humans (Neanderthals and Denisovans) appear to carry higher frequencies of language-promoting variants than ancient and modern humans, suggesting complex language capabilities emerged before the human-Neanderthal split. Cross-species genomic analysis across 170 non-primate mammalian species demonstrated convergent evolution of HAQER-like sequences specifically in vocal learning mammals, providing independent evidence for the fundamental role of these regulatory elements in complex vocal communication.
CONCLUSION These results establish a direct connection between ancient genomic changes and present-day variation in human language abilities, supporting that the genetic foundations for complex language capabilities predate Homo sapiens. The discovery that language-promoting variants show signatures of balancing rather than positive selection, combined with evidence that these variants influence prenatal brain size and birth complications, suggests an ongoing evolutionary trade-off between language capability and reproductive fitness that continues to shape human genetic variation today.
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