Ancient genes still shape our teeth: new study traces DNA behind tooth size

The research, a collaborative effort led by Dr Qing Li of Fudan University and scientists from the UK, France, the US, and Latin America, has uncovered how ancient Neanderthal DNA and modern human genetic variation continue to influence the appearance of our teeth today.

What they found

The researchers use multi-omics analyses to examine the genetic basis of variation in tooth crown dimensions. Through a large-scale genome-wide analysis of over 10 million genetic variants, they identified 18 regions in the human genome that influence tooth size, crown shape, and overall dental dimensions, offering new insight into the biology behind our smiles.

Among these, three genes stood out:

EDAR: Front-to-back effect
Variants in the EDAR gene affect tooth dimensions in an anterior-to-posterior gradient, with their impact most substantial in the front teeth and gradually decreasing toward the molars.

PITX2: Guiding tooth shape
PITX2, a well-known gene essential for tooth development, guides enamel formation and overall tooth shape. High-resolution imaging revealed that even partial changes in this gene can alter molar size and cusp patterns.

HS3ST3A1: Molar size and Neanderthal connection
The lesser-known gene HS3ST3A1 plays a direct role in molar size and crown morphology. Remarkably, some of its variants were inherited from Neanderthals, showing that ancient DNA still influences our teeth today.

The researchers confirmed their findings by replicating the associations in an independent human cohort and in mouse experiments, in which corresponding genetic regions were shown to affect molar size and crown morphology.

Our teeth carry a story written in our DNA, one that stretches back to our prehistoric ancestors. From Neanderthal interbreeding to the molecular choreography of tooth formation, this study offers a vivid reminder of how our evolutionary past continues to shape our bodies today.

Neanderthal legacy lives on

The most fascinating finding came when scientists traced the origins of the HS3ST3A1 variants. They found that the DNA segment containing this gene was introgressed from Neanderthals, meaning it entered the modern human genome through interbreeding tens of thousands of years ago. In modern populations, this ancient DNA continues to subtly shape dental traits, contributing to differences in tooth size among Europeans, Africans, and Native Americans.

Why it matters

Teeth are among the most durable human remains, and their shape has long helped scientists trace human evolution. However, until now, the genetic blueprint behind those differences was largely unknown.

“This study links modern dental variation to ancient human history,” said Dr Andrés Ruiz-Linares, a co-author of the research. “It shows how small fragments of Neanderthal DNA are still influencing how we look today — even in something as everyday as our teeth.”

Beyond anthropology, these discoveries could help dentists and geneticists understand why some people develop specific dental traits, irregularities, or growth patterns. In the long run, such insights may open the door to personalised dental treatments and genetically informed approaches to oral health care, offering hope of more effective, tailored solutions.

Reference:
Li Q, Faux P, Wentworth Winchester E, Yang G, Chen Y, Ramírez LM, Fuentes-Guajardo M, Poloni L, Steimetz E, Gonzalez-José R, Acuña V, Bortolini MC, Poletti G, Gallo C, Rothhammer F, Rojas W, Zheng Y, Cox JC, Patel V, Hoffman MP, Ding L, Peng C, Cotney J, Navarro N, Cox TC, Delgado M, Adhikari K, Ruiz-Linares A. PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans. Curr Biol. 2025 Jan 6;35(1):131-144.e6. doi: 10.1016/j.cub.2024.11.027. Epub 2024 Dec 12. PMID: 39672157; PMCID: PMC11789201.

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