From red blood cells to immune cells: there are numerous different blood cells circulating in our veins. But how and when did these originally develop? A study has now shed light on this, analyzing the gene expression of the different cell types and reconstructing a family tree. Accordingly, the evolutionary roots of our blood cells can be traced back to single-cell ancestors around 700 million years ago.
When the first multicellular life emerged, new challenges arose for the transport of resources within the organism and for the defense against invaders such as parasites and pathogens. “The development of specialized, circulating cell populations – the basis for blood and immunity – was a crucial innovation in solving these problems,” writes a team led by Yosuke Nagahata from Kyoto University in Japan. “Another innovation was the diversification of blood cells.” Different types of immune cells in the blood of vertebrates coordinate a multifaceted, multi-stage defense against pathogens. However, it was previously unclear how the different blood cells developed over the course of evolution.
From single-celled organisms to humans
To answer this question, Nagahata and his team compared gene expression in numerous different cell lines from a variety of species: from humans to mice, zebrafish and flies to sea urchins, nematodes and sponges. As a primitive comparison group, they also included several types of single-celled organisms in the analysis. “The first blood cells arose in early animals that inherited characteristics of single-celled ancestors,” explain the researchers.
Nagahata and his colleagues found the most striking similarity to single-cell organisms in macrophages. These are white blood cells that act as phagocytes and remove pathogens, cell fragments and other harmful substances and thus form a central part of the innate immune system. According to the analysis, the ancient precursors of macrophages emerged around 700 million years ago, i.e. at the time when the first multicellular animals developed.
Diversified family tree
In the next step, the researchers used gene expression to reconstruct a comprehensive family tree of blood cells over the period from 700 million years ago to the present day. Accordingly, another type of white blood cell, the mast cell, emerged from the macrophages. At that time, these played a role primarily in defending against parasites; Today they are known, among other things, as an important factor in allergies.
In the ancestors of vertebrates, mast cells also gave rise to other classes of immune cells, including natural killer cells and T cells. The red blood cells that transport oxygen throughout our body also once originated from mast cells. According to the analysis, the B cells of our immune system, on the other hand, developed directly from the original macrophages.
Ancient toolbox
“Our study shows that the complex immune system of vertebrates represents a highly specialized extension of an ancient set of instruments from the time before the first multicellular animals, which was successfully adapted to the higher demands of animal multicellularity,” reports the team. In this way, important genes from the single-cell ancestors were adopted and further developed to meet new needs.
The evolutionary origins of blood formation can still be traced today. As the researchers found using mice, macrophages and mast cells still have corresponding differentiation potential. “These findings provide insight into a reciprocal relationship between evolutionary history and current developmental pathways,” write Nagahata and his colleagues. “Our framework explains the deep continuity between the primordial unicellular organisms and vertebrate macrophages while providing a solid basis for interpreting the functional remains that have been preserved in contemporary animal development.”
Source: Yosuke Nagahata (Kyoto University, Japan) et al., Proceedings of the National Academy of Sciences, doi: 10.1073/pnas.2528110123