Human-specific genes linked to intelligence may also contribute to cancer development

Recent research led by Dr. Li Chuanyun from the Institute of Genetics and Developmental Biology at the Chinese Academy of Sciences has shed light on the dual role of human-specific genes—crucial for brain development and cognitive abilities—that can be exploited by cancer to promote tumor growth. Published in Cell Genomics, the study explores how these genes, which emerged de novo from non-coding DNA during human evolution, are typically active only in the brain and testes during early development, contributing to our uniquely advanced cognitive functions.

The team identified 37 such genes that are exclusive to humans and our closest relatives using extensive genomic and transcriptomic data across mammals. Interestingly, these same genes are hijacked in cancers, with nearly half showing abnormal activation in tumor tissues, often via extrachromosomal circular DNA (ecDNA). Functional experiments confirmed that over half of these genes facilitate tumor cell proliferation, and higher expression levels are associated with poorer patient prognosis.

"This is evolution's gamble," emphasizes Dr. Li. "Genes that helped make us smarter now also render us vulnerable to cancer." The research particularly focuses on two human-specific genes, ELFN1-AS1 and TYMSOS, which are dormant in normal tissues but become reactivated in tumors. These genes are promising targets for immunotherapy; in collaboration with Dr. Cheng Qiang, researchers developed mRNA vaccines that prompt the immune system to attack tumor cells expressing these genes. In preclinical models, the vaccines elicited strong anti-tumor responses, especially when combined with existing treatments.

Furthermore, the study challenges previous gene annotations, often missing these young genes due to their absence in model organisms or misclassification as pseudogenes. Recognizing their dual role opens new avenues for cancer therapy and deepens our understanding of human evolution and disease. This research illustrates how evolutionary triumphs can also harbor vulnerabilities, offering fresh possibilities for clinical intervention.