In a genome-wide association study of 6,169 Latin American individuals, an international team of scientists identified 32 gene regions (loci) that influenced facial features such as nose, lip, jaw, and brow shape, nine of which were entirely new discoveries while the others validated genes with prior limited evidence; one of these genes appears to have been inherited from Denisovans, an extinct sister group of Neanderthals.
A portrait of a juvenile female Denisovan based on a skeletal profile reconstructed from ancient DNA methylation maps. Image credit: Maayan Harel.
Dr. Kaustubh Adhikari, a scientist at University College London and the Open University, and colleagues analyzed CANDELA (Consortium for the Analysis of the Diversity and Evolution of Latin America) consortium data from volunteers recruited in five Latin American countries (Brazil, Chile, Colombia, Mexico, Peru).
They compared genetic information from the participants with characteristics of their face shape, quantified with 59 measurements (distances, angles and ratios between set points) from photos of their faces in profile.
They detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions.
They also found that TBX15, a gene that contributes to lip thickness, was linked with genetic data found in Denisovans, providing a clue to the gene’s origin.
“The face shape genes we found may have been the product of evolution as ancient humans evolved to adapt to their environments,” Dr. Adhikari said.
“Possibly, the version of the gene determining lip shape that was present in the Denisovans could have helped in body fat distribution to make them better suited to the cold climates of Central Asia, and was passed on to modern humans when the two groups met and interbred.”
Face profile features showing genome-wide significant association: Top – drawings indicate the features for which the 32 traits listed below were measured in the CANDELA individuals. Bottom – aggregate of the genome-wide association study (GWAS) signals detected (across all traits); the chromosomal region (and nearest candidate gene) showing strongest association to a trait is indicated above each GWAS peak (bold type marks the previously unidentified face morphology regions identified here); curved lines in the middle of the figure connect the previously unidentified face morphology region to their associated traits. Image credit: Bonfante et al., doi: 10.1126/sciadv.abc6160.
“To our knowledge this is the first time that a version of a gene inherited from ancient humans is associated with a facial feature in modern humans,” said co-first author Dr. Pierre Faux, a researcher at Aix-Marseille University.
“In this case, it was only possible because we moved beyond Eurocentric research; modern-day Europeans do not carry any DNA from Denisovans, but Native Americans do.”
“It is one of only a few studies looking for genes affecting the face in a non-European population, and the first one to focus on the profile only,” added co-first author Dr. Betty Bonfante, also from Aix-Marseille University.
One of the newly-discovered genes is VPS13B, which influenced nose pointiness.
The researchers found that this gene affects nose structure in mice, indicating a broadly shared genetic basis among distantly related mammal species.
“Research like this can provide basic biomedical insights and help us understand how humans evolved,” said co-senior author Professor Andres Ruiz-Linares, a researcher at Fudan University, University College London, and Aix-Marseille University.
“The findings could help understand the developmental processes that determine facial features, which will help researchers studying genetic disorders that lead to facial abnormalities.”
The results were published in the journal Science Advances.
Betty Bonfante et al. 2021. A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation. Science Advances 7 (6): eabc6160; doi: 10.1126/sciadv.abc6160