Researchers analyzed genomic data from over 72,000 Han Taiwanese participants in the Taiwan Biobank by comparing allele frequencies across adult age groups, according to a study published in The American Journal of Human Genetics on July 24. This approach enabled the identification of genomic signatures of ongoing natural selection and revealed disease-associated genetic variants that may have previously gone undetected.
The study examined 509,817 genome-wide variants in 72,635 Han Taiwanese individuals aged 24 to 70. Instead of focusing on genes linked to specific diseases, researchers investigated whether certain inherited variants consistently increased or decreased in frequency across various adult age groups. Their analysis identified 168 variants that deviated from neutral expectations; among these, 159 showed signs of ongoing purifying selection—an evolutionary process that gradually eliminates harmful genetic variants. Approximately 90% of these were extremely rare.
Many rare variants found were previously associated with inherited disorders. Seventy-one are classified as pathogenic or likely pathogenic in ClinVar, while others are linked to cancer, neurological conditions, cardiovascular problems, kidney disease, and other serious health issues. The identification suggests evolutionary analyses can help prioritize mutations causing disease for further research.
One notable discovery involved BRCA1—a gene known for its role in cancer susceptibility—where a rare haplotype carrying multiple protein-altering and mostly pathogenic variants appears to be under purifying selection and is becoming less common within the population. Regions near BRCA1 as well as BRCA2 and MLH1 also showed evidence of positive selection. "Evolution rarely acts on genes in a straightforward manner," said Prof. Yoko Satta of SOKENDAI (The Graduate University for Advanced Studies), Japan. "A variant increasing disease risk now might have been beneficial in a different environmental context earlier. Understanding these evolutionary trade-offs enhances our interpretation of disease-related variants in current populations."
The study found evidence that natural selection may favor genes impacting multiple aspects of human biology through pleiotropy: two genes—ATG9A and FADS2—influence numerous traits such as blood cell characteristics, liver and kidney functions, lipid metabolism, diabetes-related traits, cardiovascular metrics, and bone density.
Beyond individual findings about specific genes or traits—including red blood cell characteristics possibly shaped by historical adaptation to infectious diseases like malaria—the researchers emphasized their analytical framework could be adapted globally using other large-scale genomic datasets as more nations develop national biobanks. "Human evolution did not cease thousands of years ago," the scientists stated. "Living populations still bear its genetic imprints. Combining large biobanks with advanced genomic analysis offers a powerful new method to explore how evolution continues to shape health, disease, and human diversity."
