A recent study has found that a variant in the gene TBX1 plays a crucial role in the development of the distinct shape at the base of the skull. TBX1 is found at higher levels in humans than in closely related hominins, and low levels of TBX1 can lead to changes in skull base morphology in certain genetic conditions. This research contributes to our understanding of both human disease and evolution.
Homo sapiens, have unique features compared with other closely related hominin species and primates, including the shape of the base of the skull. The evolutionary changes underlying these features were significant in allothe function of the genes they regulate. The team focused on a specific gene called DONSON, which is involved in the maintenance of the integrity of the human genome. They found that a variant of this gene is associated with variations in the shape of the human skull base, providing a potential link between the evolution of the human brain and changes in skull morphology.
The researchers used a combination of genetic and computer analyses to identify the specific variant of DONSON that is associated with changes in skull base morphology. They found that this variant is present in about 30% of the population and is associated with a more elongated skull base. This suggests that this genetic variant may have played a role in the evolution of the human skull base and may have contributed to the development of the larger human brain.
These findings provide new insights into the genetic and molecular mechanisms underlying the evolution of the human brain and skull. The team’s discovery of the role of DONSON in skull base morphology sheds light on the complex interplay between genetics, development, and evolution in shaping the unique features of the human skull.
The identification and characterization of genomic changes are essential for understanding human development and disease. The development of the basicranial region, which is the base of the skull where it joins the bones of the neck, played a key role in the evolution of Homo sapiens. This is because we developed a highly flexed skull base, which allowed for our increased brain size. Therefore, variants that impact the development of this region are likely to have been highly significant in our evolution. The team initially looked for variants in a single letter of the DNA code, known as single nucleotide polymorphisms.The researchers found genetic variations (SNPs) that caused different gene regulation in the basicranial region in Homo sapiens compared to other extinct hominins. One of these SNPs was particularly noteworthy, as it was located in a gene called TBX1.
Using cell lines, they demonstrated that the SNP, known as “rs41298798,” is situated in a region that controls the expression levels of the TBX1 gene. They found that the “ancestral” form of the SNP, present in extinct hominins, is linked to lower TBX1 expression, while the form found in Homo sapiens is associated with higher levels of TBX1.
They then utilized a mouse model with lower TBX1 expLead author Noriko Funato explains that the study found distinct changes in the base of the skull and premature hardening of a cartilage joint in mice with the “Tbx1” gene knocked out. These changes restricted the growth ability of the skull and were similar to the basicranial morphology of Neanderthals. The study also found that these morphological changes are reflected in human genetic conditions associated with lower “TBX1” gene dosage, such as DiGeorge syndrome and velocardiofacial syndrome, indicating the significance of this genetic variant in the evolution of our unique skull.The discovery of a genomic variant that affects the expression of the TBX1 gene is significant for understanding human evolution and genetic conditions associated with lower TBX1 expression. This finding has the potential to improve our understanding and management of these conditions.
