From: user5108@newsgrouper.org.invalid   
      
   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 O’Brien, 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 FOXP2’s   
   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 human–Neanderthal 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 species’ 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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