Claw gene remnants point to legs in snake ancestors

Nonfunctional remnants of genes (pseudogenes) can often provide evidence of the evolutionary history of life. I once wondered if snakes have any pseudogenes that pointed to a time when they once had legs, a conclusion suggested by comparative genetics and the fossil record. but I had trouble imagining what kinds of genes would provide a record of this hypothetical history. After all, there aren’t ‘leg’ genes or ‘arm’ genes, as the genes involved in making limbs participate in the development of a number of body structures.

However, I was excited to learn that there are indeed some genes that appear to be specific to a portion of the limbs: the claws. These genes, known as keratins, seemed like good candidates for investigation, and led to me to study the evolutionary history of snakes. But first, let me share a few details about keratins to give you some context

Keratins are known as structural proteins, meaning they form physical structures that are often visible to the naked eye. Though proteins are involved a wide variety of functions, ranging from vision to carrying oxygen to tissues throughout your body, most do not clump together in large enough quantities to be visible to the naked eye. Keratins, on the other hand, are often quite visible, and include things as different as hair, nails, feathers, porcupine quills and rhino horns.

Feathers

Porcupine quills

Rhino horns

Claws are also made of keratin, just like your nails, and a pair of studies found that at least two of these keratins appear to be localized almost entirely in the claws of lizards [1,2].

Gene expression of various lizard keratins

HA1 expression in claw of a lizard (arrows)

In addition to showing that these keratin genes, HA1 and HA2, are turned on in the fingers and toes of lizards, and staining techniques demonstrated that HA1 is produced at the base of lizard claws, the researchers showed that the HA1 gene is present and intact in every lizard that they looked at, except for one. The exception? A legless, and therefore clawless, lizard, known as the slow worm [3]. They didn’t find the gene completely absent in this animal, however, but present in the genome with two mutations that lead to a nonfunctional keratin. This points to a time when legless lizards and limbs and claws, consistent with studies of DNA and developmental biology.

HA1 gene alignment showing inactivating mutation in legless lizard (Anguis)

Anguis fragilis, the slow worm

Furthermore, they tried to look for the gene in snakes, but to no avail. I, on the other hand, benefit from working in the world of genomics. Since this initial paper was published, multiple snake genomes have been sequenced and assembled, so I made an effort to look for both claw keratin genes, HA1 and HA2, in eight species of snakes.

Whereas I could not find HA2 in the snakes, no matter how hard I looked, I found a degraded portion of HA1 in the genomes of six of the snake species [4]. What was perhaps even more exciting, is that all of these species, which included species as different as a python, vipers, rattlesnakes, and a cobra, all shared the exact same disabling mutation: an eight letter (base pair) insertion in the first portion of the gene. This suggests that these snakes share a common ancestor that once possessed a functional claw keratin gene, along with claws, digits and limbs.

Python bivittatus, Burmese python

Protobothrops mucrosquamatus, brown spotted pit viper

Crotalus horridus, timber rattlesnake

Ophiophagus hannah, king cobra

This provides another exciting example where DNA and fossils tell the same story: one where a group of lizards evolved into the legless snakes that we love (or loathe) today.

Question for Creationists

Why would the Creator create a broken claw keratin gene in legless snakes and a legless lizard? Wouldn’t it make more sense to simply create them without a broken gene? If these animals evolved from ancestors with claws and legs after the flood, why and how did they lose their legs so quickly? Why do they all share the same mutation, even though they are different ‘kinds’? Is it just a coincidence that snakes have remnants of a claw gene, show DNA evidence of descending from legged lizards and also have fossil evidence of formerly possessing legs?

References

1. Eckhart, L., Dalla Valle, L., Jaeger, K., Ballaun, C., Szabo, S., Nardi, A., … & Tschachler, E. (2008). Identification of reptilian genes encoding hair keratin-like proteins suggests a new scenario for the evolutionary origin of hair. Proceedings of the National Academy of Sciences, 105(47), 18419-18423.

2. Alibardi, L., Jaeger, K., Valle, L. D., & Eckhart, L. (2011). Ultrastructural localization of hair keratin homologs in the claw of the lizard Anolis carolinensis. Journal of morphology, 272(3), 363-370.

3. Dalla Valle, L., Benato, F., Rossi, C., Alibardi, L., Tschachler, E., & Eckhart, L. (2011). Deleterious mutations of a claw keratin in multiple taxa of reptiles. Journal of molecular evolution, 72(3), 265-273.

4. Emerling, C. A. (2017). Genomic regression of claw keratin, taste receptor and light-associated genes provides insights into biology and evolutionary origins of snakes. Molecular phylogenetics and evolution, 115, 40-49.