Your body depends on a continuously moving stream of blood in order to stay alive. Why? Because it is the blood which carries the oxygen needed to fuel the electron transport chain in the mitochondria of all your cells. The continuous movement of the blood, thanks to the heart, coupled with the continuous supply of oxygen to the blood, thanks to the lungs, means all of the body cells have the ability to continuously generate ATP by their mitochondria. And that ATP is needed to run the variety of molecular machines inside the cells.
But the liquid portion of the blood, the plasma, can only dissolve and carry about 3% of the body’s oxygen demand. The other 97% of the oxygen must be carried by the blood transport protein, hemoglobin. Hemoglobin is composed of four amino acid chains known as globin, each one with a red pigment molecule known as heme embedded inside. The heme binds on ionized form of iron, which in turn is where the oxygen binds. Every red blood cell is packed with hemoglobin, thus oxygen.
What this all means is that your large, complex, multicellular body exists because of the globin protein. It is the globin, with its ability to bind, hold, and release oxygen that facilitates its existence.
In The Design Matrix, I used this fact as part of a heuristic example to illustrate the plausibility of front-loading evolution. That is, while globin is essential for evolving a body like ours, it is not needed for unicellular life. Single-celled organisms do not need or have blood and blood vessels, because the mitochondria of such cells can easily get the oxygen from their surroundings. So how could a front-loading designer ever hope to use evolution to unfold a body like ours if globin would be of no use to single-celled life?
The answer is simple.
Give globin a function in unicellular life such that when mutlicellular life began to unfold to the point where some form of blood and circulatory system was needed, globin would already exist to facilitate the transition. And sure enough, as I explain in the book,
Globin occurs in all the kingdoms of living organisms, even though its distribution is episodic among the non-vertebrate groups in contrast to vertebrates. In bacteria, it is used for oxygen sensing and to control nitric oxide levels. Also, in some cyanobacteria, it is used to increase the efficiency of oxygenic photosynthesis. Yet the episodic distribution among microorganisms indicates that globin is not essential for microbial life, like it is for vertebrate life.
So let me expand on this.
The globin domain is actually quite special in that it, along with another domain known as the PAS domain, are the only two domains among the 1000 or so domains in life’s toolkit that can reversibly binding O2 to the heme iron.
In both bacteria and archaea, it has been determined that the globin domain can be attached to other protein domains allowing the cell to link oxygen binding with some other function. In other words, the globin becomes a “biological heme-based sensor” that couples oxygen content in the environment to patterns of gene expression and/or cell motility and behavior. One example is the phenomenon of aerotaxis, the movement of a cell or organism toward or away from oxygen, where the globin domain is plugged into the chemotaxis pathway associated with the flagellum!
Because of the modular nature of proteins, the globin domain could be removed from its partner domain by recombination or transposition, allowing it to exist as a stand-alone to evolve into something like hemoglobin:
From figure 3 in ref .
Let my now quote from one research paper that explores the use of globin as “biological heme-based sensor” :
Protoglobins have shown “flexibility” with their broad ligand range and their sensitivity to oxygen predisposes them to functioning in low oxygen environments. Thus they appear to be the molecular fossil that thus far, most closely resembles the hemoglobin that was present in LUCA. As the atmospheric contents began to shift, however, and the oxygen levels rose, so too did the protoglobin evolve the capability to transport and store this oxygen more efficiently to maintain oxygen homeostasis, eventually forming the hemoglobin in our blood and the myoglobin in our muscles.
As the protoglobin helped give life to LUCA, its globin descendents allowed higher organisms to evolve by maintaining their core function of oxygen homeostasis. This collective evolution of hemoglobin, myoglobin, neuroglobin, and cytoglobin made life possible; whether by aerotaxis, gene regulation, detoxification, sequestration, or transport, the inter- and intracellular balance of oxygen was key to the evolution of humans. Thus, it only seems logical that globins be found in most mammalian tissues and in the blood that bathes them.
This form of front-loading is brilliant. Globin is not given some “add-on” function from the perspective of front-loading, as if it was an afterthought, but plays key homeostatic roles in the life of single-cells. It is this key homeostatic role that is then amplified and unfolded in the evolution of blood. In other words, globin wasn’t merely available to facilitate the evolution of blood, it helped to guide the blind watchmaker in forming blood.
The same research paper also notes:
This protoglobin is thought to be present in organisms possibly as far back as the Last Universal Common Ancestor, or LUCA, the source of all life on Earth. LUCA is believed to have been a metabolically “flexible” single-celled organism with the ability to utilize oxygen for energy before free oxygen even existed in the air, thus preceding oxygenic photosynthesizers. The idea that an organism existed with the capacity to “breathe” O2 before there was a real need to, however, goes against the textbook viewpoint . In his recent book , Nick Lane argues that LUCA likely made use of a hemoglobin-like protein to manage oxygen homeostasis and an antioxidant enzyme like superoxide dismutase (SOD) to protect itself. This hemoglobin would not have to deal with much oxygen at all, but rather very low levels of oxygen, perhaps similar to the role of leghemoglobin in nitrogen-fixing bacteria.
We can expand on this from a telic perspective. If the planet was seeded with a heterogeneous consortium of cells, designed to take root, where some cells were endowed with photosynthetic ability, then the existence of globin in other cells would have enabled them to form communities. In other words, globin, acting as a sensor to detect nearby photosynthetic cells, could have facilitated symbiotic relationships among the original cells.
This scenario is supported by the recent evidence that shows both aerobic respiration and oxygenic photosynthesis to be much older than convention would have it. Not to mention the evidence that quorum sensing can involve very different species of bacteria.
So the Rabbit continues to come into better focus as he weaves among the basketball players– a planet originally seeded with a consortium of sophisticated cells takes root and develops symbiotic relationships which ultimately unfold into much more complex life forms under the guidance of the original state. Evolution is a beautiful design.
1. Freitas, Tracey Allen K; Saito, Jennifer A.; Hou, Shaobin; Alam, Maqsudul. 2005. Globin-coupled sensors, protoglobins, and the last universal common ancestor. Journal of Inorganic Biochemistry 99:23-33.