Does Collagen Provide Evidence for Design?
Collagen is a family of proteins that includes the most abundant protein in our body; this family contributes structural strength to connective tissue in places like tendons, ligaments, skin, and muscles. From a scientific perspective, this protein’s assembly and function require a lot of complex details.
Is it more reasonable to conclude that collagen was assembled by undirected evolutionary processes or by intentional design? That question may be answered by exploring the processes involved in the formation of this just-right protein.
Protein Formation Requirements
Life stores and transcribes amazing amounts of information using the “central dogma of molecular biology,” an explanation of the flow of genetic information within a biological system. This dogma says that DNA contains coded information that is transcribed to messenger RNA, which becomes a template for making specific proteins. These proteins have chains of 20 amino acids in specific orders and lengths. Sometimes, these chains bind to one another, either with similar chains or different ones. The resulting amino acid arrangements yield many different functions (like the way letters arranged into writings convey different meanings).
Collagen Formation Requires Even More Steps
As amazing as this assembly of information is, some protein functions require even more assembling. An example is the collagen family, where much more detailed assembly must happen to create function that strengthens structure in connective tissues and bones.1 Could this protein family have developed by undirected evolution, or does it reflect design? To answer this, consider how much has to happen to make functional collagen.
Steps for Amino Acid Chain Formation
First, the correct amino acid chains must form (per the central dogma process discussed above). These chains are mostly tagged for export out of cells. Then, three of these chains must find each other and match up to form a triple helix (like three winding staircases wrapping around each other). This finding and matching is not simple, a point noted even in an article claiming evolutionary origins for collagen.2 This helix forms partly because the amino acid glycine repeats every third spot for long sections. The triple helix also requires certain proline and lysine amino acids to be converted into hydroxyproline and hydroxylysine, amino acids that aren’t among the usual 20. This conversion is catalyzed by two enzyme proteins (lysyl hydroxylase and proline hydroxylase), which require the reducing agent ascorbic acid (vitamin C in human nutrition).
Steps for “Gluing” Crosslinks
After the triple helix forms, strands must be “glued” together as crosslinks. This process requires the copper enzyme lysyl oxidase, which I studied in my biochemistry doctoral dissertation research. Copper is transported into cells, targeting certain enzymes while not poisoning anything. This copper transport happens via cell membrane receptors and copper chaperones—a feature I learned when I contributed to early research on this process.3 Lysyl oxidase leaves the cell after it’s made and functions outside the cell, and some amino acid chain connections are broken by protease enzymes. Then, lysyl oxidase grabs a vitamin-like cofactor (pyrroloquinoline quinone/PQQ) and catalyzes reactions in certain lysines in collagen and another structural protein (elastin). Next, the altered lysines undergo nonenzymatic reactions with other lysines or certain other amino acids that are nearby. This happens between strands of one collagen molecule and between strands of different collagen molecules (to convert multiple three-stranded ropes into fibrous networks). Besides all this, other modifications that I won’t describe also occur. Lastly, collagen must fit in matrixes like bones, tendons, and blood vessels.
Why It Must All Come Together
As described above, many moving parts blend in coordinated fashion to make functional collagen. From an evolutionary perspective, could a primitive collagen have originated by using only some moving parts to be at least somewhat functional? If yes, could this version have then evolved into better versions? These questions can be addressed by working backward. Specifically, how much of collagen’s properties can be lost before there is terrible malfunction or fatality? Well, some small defects seem somewhat tolerable. For example, my research finds that in young adult women, moderate copper deficiency can partially reduce crosslinking.4 Nevertheless, these women still seem healthy, and though osteoporosis and cardiovascular disease risk may rise, the collagen still works fairly well. So, a primitive collagen without full crosslinking could have existed.
However, this example only mildly diminishes one relevant process (copper incorporation into lysyl oxidase). A larger collagen crosslink decrease, such as in severe copper deficiency in livestock or experimental animals, produces heart or blood vessel rupture. Similarly, in vitamin C deficiency (scurvy), malformed collagen can produce fatal blood vessel breaches. Also, in genetic collagen malformations, lethality, or very low collagen functionality, can result from small changes—even in as little as one amino acid.5 Thus, collagen can’t change much and still function well.
Steps Required for Evolutionary Development of Collagen
Since well-functioning collagen requires the coordination of various processes, invoking design seems reasonable. If collagen was instead created by undirected evolution, here’s what had to happen:
- A gene evolved for an amino acid sequence with no function, a non-collagen function, or a weak collagen function (though, as mentioned above, this last idea leads to problems). Another possibility is that multiple genes for other proteins merged to make a collagen (though this requires explaining what drove that fortuitous event).
- The collagen gene transformed into multiple genes coding for the various collagen forms.
- Other genes evolved for three enzymes that modify collagen but mostly ignore other proteins.
- For one of these enzymes, lysyl oxidase, proteases arrived to break the amino acid chain only in certain places.
- All three collagen-modifying enzymes took a shape that binds cofactors (copper, PQQ, or ascorbic acid).
- Most collagen and the modifying enzymes were tagged to leave cells.
- These enzymes plus cofactors reacted the right way with only certain lysines or prolines (amino acids) in collagen, but not with others, nor with these amino acids in almost all other proteins.
- Certain lysines lined up in just-right positions. That’s because after lysyl oxidase starts the crosslinking process, the modified lysines have to react with other lysines that are close by (without enzyme help).
- The copper transport system evolved so that copper goes to only certain enzymes like lysyl oxidase without causing toxicity elsewhere.
- Several miscellaneous collagen modification mechanisms developed.
- A number of different matrixes were present in which to sit the collagen.
- Each of these steps developed without “knowing” the other steps would evolve.
- Finally, if each step formed gradually over long times, natural selection preserved each functional improvement (even though all the steps had to be working well for collagen to function properly).
Despite the unlikelihood of all these considerations having been met, researchers have proposed collagen evolution sequences.6 Each proposal assumes a primitive collagen, but no such collagen currently exists in lower life-forms, where collagen resembles collagens in higher life-forms. No direct evidence exists for this earlier, primitive collagen. Even if it did exist, researchers haven’t given a rationale for what drove its origin. Moreover, although evolutionary events have been proposed for what happened next, no statistical probabilities have been given for the events’ likelihood. The crosslinking study cited from Scientific Reports does mention the improbability of step 8 from above but only to say that the lysine arrangement requires evolutionary preservation. The authors fail to explain how the arrangement originated.
Evolution or Creation?
What can be concluded about the extremely detailed and coordinated processes needed to make collagen? From an evolutionary perspective, no existing models show a likelihood that undirected evolution could produce the detailed and coordinated events required for collagen formation. Instead, all these detailed, coordinated events strongly point to the work of an intelligent Designer.
1. Matthew D. Shoulders and Ronald T. Raines, “Collagen Structure and Stability,” Annual Review of Biochemistry 78 (July 7, 2009): 929–958, doi:10.1146/annurev.biochem.77.032207.120833; Raymond P. Boot-Handford and Danny S. Tuckwell, “Fibrillar Collagen: The Key to Vertebrate Evolution? A Tale of Molecular Incest,” BioEssays 25, no. 2 (February 2003):142–151, doi:10.1002/bies.10230; Fernando Rodriguez-Pascual and David Anthony Slatter, “Collagen Cross-Linking: Insights on the Evolution of Metazoan Extracellular Matrix,” Scientific Reports 6 (November 23, 2016): 37374, doi:10.1038/srep37374.
2. Boot-Handford and Tuckwell, “Fibrillar Collagen.”
3. Michael D. Stevens, Robert A. DiSilvestro, and Edward D. Harris, “Specific Receptor for Ceruloplasmin in Membrane Fragments from Aortic and Heart Tissues,” Biochemistry 23, no. 2 (January 1, 1984): 261–266, doi:10.1021/bi00297a014; Robert A. DiSilvestro, “Copper Activation of Superoxide Dismutase in Rat Erythrocytes,” Archives of Biochemistry and Biophysics 274, no. 1 (October 1989): 298–303, doi:10.1016/0003-9861(89)90442-6.
4. Robert A. DiSilvestro, Joshua Selsby, and Kristina Siefker, “A Pilot Study of Copper Supplementation Effects on Plasma F2α Isoprostanes and Urinary Collagen Crosslinks in Young Adult Women,” Journal of Trace Elements in Medicine and Biology 24, no. 3 (July 2010): 165–168, doi:10.1016/j.jtemb.2010.02.003.
5. D. H. Cohn et al, “Lethal Osteogenesis Imperfecta Resulting from a Single Nucleotide Change in One Human Pro Alpha 1(I) Collagen Allele,” Proceedings of the National Academy of Sciences, USA 83, no. 16 (August 1,1986): 6045–6047, doi:10.1073/pnas.83.16.6045; Boot-Handford and Tuckwell, “Fibrillar Collagen.”
6. Boot-Handford and Tuckwell, “Fibrillar Collagen;” Rodriguez-Pascual and Slatter, “Collagen Cross-Linking.”