The origin, evolution, and dynamics of micropeptides in the immune system

Our immune systems — and those of all animals — are among the most rapidly evolving parts of our bodies, due in part to the evolutionary “arms race” we face against fast-evolving viruses and other pathogens. But how new immune-related genes arise in evolution remains poorly understood. Li Zhao, Ph.D., and Mandë Holford, Ph.D., are leading a project to better understand how immune genes that code for tiny proteins known as micropeptides arise in evolution. The team will characterize immune-related micropeptides in humans and in fruit flies, focusing specifically on micropeptides that play a role in the innate immune system, our first line of defense against pathogens. Humans have both an innate and an adaptive immune system, while insects have only innate immunity. They will also focus on an evolutionarily new micropeptide in the fruit fly to better understand its function in the immune system and how it evolved.

This project is part of the 2021 Micropeptides and immunity cohort

Our genomes contain vast amounts of DNA that remain poorly understood. A recent arrival on the scene of genomic “dark matter”: micropeptides, tiny proteins coded by tiny genes that had long escaped notice due to their size but that appear to be present in large numbers in our genome and that of every other living thing. These small molecules likely play roles in many different biological processes; scientists are recently uncovering their influence in several different diseases and in the function of the immune system. Scientists in the Micropeptides cohort are shedding new light on how micropeptides influence immunology, in health and in disease.