An ancient immune programme older than animals themselves

The immune system is one of the key innovations of animal life. But part of the genetic programme behind it may be much older than animals themselves.

A study led by Kyoto University and the Institute of Evolutionary Biology (IBE, CSIC-UPF) has reconstructed the evolutionary history of blood cell lineages by comparing which genes are active in very distant organisms, from mammals and zebrafish to sponges and unicellular relatives of animals.

Infographic showing how the first blood cells probably resembled macrophages, with a diagram from a unicellular ancestor to multicellularity and a macrophage-like immune cell. It also shows a phylogenetic tree built from active genes in mammals, zebrafish, invertebrates, sponges, Capsaspora and Salpingoeca.

The results, published in PNAS, suggest that evolution did not invent animal immunity from scratch. Instead, it reused and reorganised older cellular programmes into new functions.

Infographic explaining that the gene Fos may have helped preserve an ancestral protective programme by reusing a unicellular genetic toolkit. It also shows how an ancestral cell may have given rise to modern blood and immune cell lineages, including mast cells, T cells, NK cells, B cells and red blood cells.

Key ideas

The first blood cells were probably macrophage-like
The study suggests that the earliest blood cells were mobile, defensive cells similar to modern macrophages.
This programme may be older than animals
The first immune-like blood cells may have appeared around 700 million years ago, during the transition towards multicellular life.
Fos appears to be a key gene
The gene Fos may have helped regulate this ancient protective programme, reusing genetic tools already present in unicellular ancestors.
Blood development still carries evolutionary traces
Modern haematopoiesis may still reflect the order in which blood-cell types emerged during evolution.

Reference article

Nagahata Y, Nishimura Y, Kaitani R, Leong JCK, Oda-Ishii I, Kohtsuka H, Abe S, Ishida T, Carmona-Rivas M, Najle SR, Casacuberta E, Ikuta K, Miura T, Ogasawara M, Irie N, Satou Y, Ruiz-Trillo I, Kawamoto H. Animals have expanded the evolutionary legacy of unicellular ancestors in blood cells. PNAS (2026).

About the author

Sonia Liñán has over 20 years’ experience in science communication. She believes communication is a powerful tool for social change and works to make research clearer, more engaging, more diverse, and more inclusive. She is currently Coordinator of Digital Media and Scientific Affairs at PRBB. Previously, she led communications for the EMBIMOS research group (ICM-CSIC), was part of the coordination team behind the MINKA citizen-science observatory, and headed the Digital Marketing and Communications team at Biocat. More information on LinkedIn.