An example of a signalling cascade
A common theme in molecular biology is the idea of genetic cascades. Such cascades describe a system of genetic interactions, in which one gene activates another, which triggers another, and so on and so forth. A major claim from the intelliegent design community is that genetic cascades are irreducibly complex as all participating genes and biochemical molecules have to be present or the cascade cannot function. Evolution by natural selection would be unable to achieve such a cascade as it can only create complexity via functional intermediates.
Wait, what does irreducibly complex mean?
According to Behe (1996), a irreducible complex system “is composed of several interacting parts that contribute to the basic function, and where the removal of any one of the parts causes the system to effectively cease functioning. An irreducibly complex system cannot be produced gradually by slight, successive modifications of a precursor system, since any precursor to an irreducibly complex system is by definition nonfunctional.”
Extending this argument to cascades, Behe (1996) argues that “because of the nature of a cascade, a new protein would immediately have to be regulated. From the beginning, a new step in the cascade would require both a proenzyme and also an activating enzyme to switch on the proenzyme at the correct time and place. ” In other words, each step of the cascade requires several participants to be present to function, and thus making the whole cascade irreducibly complex.
He uses two examples genetic cascades which he considers to be irreducibly complex, namely the blood clotting cascade, and the complement system.
For this post, I will be focusing on the claim that the complement system is irreducibly complex.
What is the complement system?
The complement system is part of the immune system, which helps organism clear pathogens within it. Involving many small proteins (mostly synthesised by the liver), the complement systems aids antibodies and phagocytes (cells that engulf and therefore ridding of pathogens) in elimination foreign agents in the body (Janeway et al., 2001).
Immunologists have often described the vertebrate complement system as acting acting in three pathways– the Lectin Pathway, Alternative Pathway and the Classical Pathway (See Figure 1).
The Three Pathways of the Complement System
Figure 1: The three pathways of the Vertebrate Complement System. Note that the letters (eg: B, C3, MBP) represent different proteins. Additional letters behind the proteins indicate a cleavage product (eg: C3a and C3b is formed from the breakdown of the C3 protein).
As shown from Figure 1, each of the three pathways require an enzyme, C3 convertase, to function*. In other words, the C3 convertase is required to activate the complement proteins. For the lectin and classical pathways, C2b functions as the C3 convertase; for the alternative, the proteins complex consisting of C3b and D acts as the C3 convertase.
Why does Behe (1996) say that is system is irreducibly complex?
On the surface, the complement system seems to be irreducibly complex because
a) all the precusor proteins (ie C3, B, D, MBP, MASP1, MASP2, C2 and C1) require C3 convertase to function
b) C3 convertase has no function beyond activating the precursor proteins.
Hence, since these two components (precursor proteins and C3 convertase) are required at the same time to assemble a functional system, the vertebrate complement system would be irreducibly complex.
In addition to that, humans who lacked C3 convertase are more prone to infections from Haemophilus influenzae and Streptococcus pneumonae. So it appears that Behe (1996) is right.
But….
What Behe (1996) failed to realise is that (i) invertebrates have a complement system that lacked some precursors and (ii) there are vertebrates with intermediates of the complement system, suggesting a possible evolutionary pathway.
i) The complement system of invertebrates
In the study of the Japansese sea squirts ( Halocynthia roretzi), Ji et al. (1997) found that the sea squirts have only the lectin pathway, suggesting that the lectin pathway is evolutionarily the oldest pathway among the three of the complement system. Another interesting thing find is that the sea squirts do not produce the C2 protein, and therefore cannot not produce the vertebrate C3 convertase. However, the complement system functions just fine.
Remember Behe’s (1996) definition of irreducible complexity– if “one or more parts” of the irreducible complex system is removed, the system would be non-functional. However, the invertebrate complementary system lacks several parts of the vertebrate one, and it works just fine.
ii) Possible evolutionary pathway
For the sea squirts, it appears that that the MASP itself acts as the C3 convertase (Ji et al., 1997). Mammalian MASP can also act as C3 convertase, although it is not efficient. In other words, it is not hard to hypothesise that some wat along the evolutionary tape, the protein C2 (and thus C2b) took over MASP’s role as C3 convertase, diminishing’s the MASP’s role as one.
The adoption of C2b as C3 convertase is hypothesised to not only allow the retention of the lytic pathway, but also allowed the formation of the classical pathway. This hypothesis is further strengthened by the fact that the proteins involved in the invertebrate and vertebrate systems are homologous (ie loosely speaking, highly similar), so this complexity of the vertebrate complement system could have arisen via gene duplication (Zarkadis et al., 2001).
Conclusion
Since the complement system has been shown to function in other organisms despite lacking some components of the vertebrate complement system, the vertebrate complement system is shown to be NOT irreducibly complex.
References
Behe, M.H. (1996) Darwin’s Black Box
Janeway Jr., C.A., Travers, P., Walport, M., Shlomchick, M., J. (2001) Immunobiology (5th edition)
Ji, X., Azumi, K., Sasaki, M., Nonaka, M. (1997) Ancient origin of the complement lectin pathway revealed by molecular cloning of mannan binding protein-associated serine protease from a urochordate, the Japanese ascidian, Halocynthia roretzi. PNAS USA 94, 6340-6345
Zarkadis, I.K., Mastellos, D., Lambris, J.D. (2001) Phylogenetic aspects of the complement system. Developmental and Comparative Immunology 25, 745-762
*Please note that C4 is cleaved into C4a+ by MASP or C1, rather than C3 convertase.
Tags: complement, intelligent design, irreducible complexity, That can't be true
