NHGRI logo


updated: September 27, 2022


Substitution, as related to genomics, is a type of mutation in which one nucleotide is replaced by a different nucleotide. The term can also refer to the replacement of one amino acid in a protein with a different amino acid.



Substitution. It's always fascinated me how tiny changes in one's genome, like a simple substitution, can have such profound effects on human health. Changing a single nucleotide will change the amino acid sequence, which can impact how the protein it forms will look and act. Most of these small changes don't have a meaningful impact on human health or appearance, but we're quickly learning how to find the ones that are important. Knowing how small genetic changes work can then help us to discover new treatments for diseases. The differences between people's appearance comes from these seemingly miniscule changes in our genetic code, which I think should remind us that all humans share nearly all of our genetic material.

Benjamin Berkman
Benjamin E. Berkman, J.D., M.P.H.

Deputy Director

NHGRI Bioethics Core