The 89th Annual Meeting of the American Association of Physical Anthropologists (2020)

The Human NF1 Locus:  A Unique Hominin Genotype with Potential Evolutionary Significance


1Sociology and Anthropology, Western Illinois University, 2Director, The Neurofibromatosis Institute

April 18, 2020 2:15PM, Platinum Ballroom Add to calendar

The autosomal dominant genetic disorder, Neurofibromatosis Type 1 (NF1), derives from the human NF1 gene, which influences many of the physical, cognitive, and behavioral traits that distinguish Homo sapiens from other fossil and extant primate taxa. The ordinary, non-mosaic NF1 disorder results from a germline pathogenic mutation in the ~300,000 bp NF1 supergene and is characterized by behavioral elements, benign tumors of the nerve sheath (e.g., neurofibromas), macrocephaly, short stature, heat intolerance, learning disabilities (involving speech, spatial reasoning, executive functioning, and musicality), and resistance to obesity, diabetes, alcoholism, and opiate addiction. The disorder is fully penetrant, but heterozygosity allows for unaffected offspring and the morbid phenotype requires additional changes, such as somatic mutation of the normal allele. It is thus progressive, and the ultimate phenotype is highly variable, moderating the disorder’s impact on reproductive success.

New research reveals that both the wild-type human NF1 allele and resulting neurofibromin protein are unique compared to those of other extant primates, yet the modern human NF1 coding sequence is identical to those from Neanderthal, Denisovan, and early modern human specimens. DNA sequences that would replicate the chimpanzee (ancestral) neurofibromin amino acid sequence have never been documented among modern humans, aside from a somatic mutation in tumor tissue. No non-human primate has been documented to have the NF1 syndrome, but it is the likely diagnosis for the Cro-Magnon 1 specimen. These data suggest a complete and functionally-significant replacement of the ancestral NF1 allele prior to the emergence of Homo sapiens in the hominin lineage.

Slides/Poster (pdf)