The 700-million-year history of our blood cells

Kyoto, Japan -- Almost all animal species -- including humans -- have blood cells, but between different species our blood tells different stories. The lineage and components of blood cells vary widely, and this variety is a testament to how animals have evolved to protect themselves from infectious diseases.

Thanks to advances in hematology and immunology, we now have detailed knowledge of the components and functions of both human and mouse blood cells. However, their evolutionary history has remained largely unknown. This inspired a team of researchers at Kyoto University to investigate when and how blood cells originated, and how they diversified.

The team began by developing a new analytic method to compare gene expression profiles across various cell lineages and animal species. With this they were able to construct phylogenetic trees of cell lineages and estimate the evolutionary history of these lineages in animals. They also included unicellular organisms in their comparison in order to trace the origin of blood cells back to possible single-celled ancestors.

Among the various lineages of human blood cells the team observed, macrophages showed the most striking resemblance to unicellular organisms, suggesting that early blood cells were macrophage-like. They then traced the gene FOS -- commonly expressed in blood cells across animal species -- back to a single-celled ancestor that lived 700 million years ago, suggesting that the first blood cells emerged around the same time as the onset of multicellular animals.

This finding implies that early animals generated the first blood cells by repurposing genetic material inherited from single-celled progenitors. The team's analysis also revealed that mast cells branched off from the macrophages, and that prototypic T cells and red blood cells subsequently branched off from the mast cells. Furthermore, prototypic B cells branched off from the macrophages after the segregation of mast cells.

Ultimately, the scientists was able to reconstruct the family tree of blood cells over the 700-million-year span, revealing that evolutionary history has been imprinted in our bodies as differentiation pathways of these cells. This work illustrates that the blood and immune cells circulating in our bodies can be considered a successful extension of the legacy left to us by our single-celled predecessors.

"I feel deeply moved by these findings, which represent the culmination of our work and illustrate that the differentiation pathways of vertebrate blood cells reflects the 700-million-year evolutionary history of these cells," says team leader Hiroshi Kawamoto.

"When I let it sink in that this legacy from so long ago is circulating within my body as blood cells, I feel closer to our distant ancestors," adds first author Yosuke Nagahata of the Institute of Evolutionary Biology, Spain.

The researchers expect that the method developed in this study could help unravel the evolutionary origins of diseases such as cancer, leading to a better understanding of mechanisms and the development of new treatments.

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The paper "Animals have expanded the evolutionary legacy of unicellular ancestors in blood cells" appeared on 29 May 2026 in Proceedings of the National Academy of Sciences of the United States of America, with doi: 10.1073/pnas.2528110123

About Kyoto University

Kyoto University is one of Japan and Asia's premier research institutions, founded in 1897 and responsible for producing numerous Nobel laureates and winners of other prestigious international prizes. A broad curriculum across the arts and sciences at undergraduate and graduate levels complements several research centers, facilities, and offices around Japan and the world. For more information, please see: http://www.kyoto-u.ac.jp/en