Emergence and evolution of the renin–angiotensin–aldosterone system

Abstract

The renin–angiotensin–aldosterone system (RAAS) is not the sole, but perhaps the most important volume regulator in vertebrates. To gain insights into the function and evolution of its components, we conducted a phylogenetic analysis of its main related genes. We found that important parts of the system began to appear with primitive chordates and tunicates and that all major components were present at the divergence of bony fish, with the exception of the Mas receptor. The Mas receptor first appears after the bony-fish/tetrapod divergence. This phase of evolutionary innovation happened about 400 million years ago. We found solid evidence that angiotensinogen made its appearance in cartilage fish. The presence of several RAAS genes in organisms that lack all the components shows that these genes have had other ancestral functions outside of their current role. Our analysis underscores the utility of sequence comparisons in the study of evolution. Such analyses may provide new hypotheses as to how and why in today's population an increased activity of the RAAS frequently leads to faulty salt and volume regulation, hypertension, and cardiovascular diseases, opening up new and clinically important research areas for evolutionary medicine.Electronic supplementary materialThe online version of this article (doi:10.1007/s00109-012-0894-z) contains supplementary material, which is available to authorized users.

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

“…Teleosts represent the taxon with the most primitive renin and RAS known (14). If functionally conserved, the fish RAS may also function in ion homeostasis and development.…”

The evolution of evolutionary molecular medicine

“…Likewise, the molecules, cellular functions, organs, complex organization of muscles, bones, sensory organs, and nerves in vertebrates derive in an unbroken line from ancestors millions of years ago. Much of modern man's biology dates back to the origins of life; a complete understanding of this biology can only be appreciated with an evolutionary perspective [6].…”

Too Much Salt and How We Can Get Rid of It

“…Furthermore, black people show increased sodium retention compared to white people after high dietary sodium intake [19], which, from an evolutionary perspective, makes sense in terms of conserving salt in a low-salt, hot environment. However, with the use of salt to spice up food, combined with low potassium levels, the RAA system might possibly have functionally altered or be somehow in ‘constant overdrive', as Fournier and co-workers stated in a recent publication [17]. …”

“…Aldosterone does not only conserve sodium, but also induces the excretion of potassium in order to prevent dangerous hyperkalemias, especially in cases of potassium rich diets, e.g., the paleolithic diet [16]. Studies on the RAA system evolution suggest its emergence about 400 million years ago [17]. A highly active RAA system was important for survival of our ancestors as it ensured salt and volume homeostasis during the different stages of evolution, up until the Homo sapiens appeared.…”