and i quote, from the article:
Dr. Behe described the results as "piddling." He wondered whether the receptors with the intermediate mutations would be harmful to the survival of the organisms and said a two-component hormone-receptor pair was too simple to be considered irreducibly complex. He said such a system would require at least three pieces and perform some specific function to fit his notion of irreducibly complex.
Dr. Behe, the "main advocate of intelligent design", in dismissing the work reported in the article as "piddling" has made my day. i've not had such a hearty geek laugh for so long! Sigh.
The article describes the following paper published in the journal Science. The paper describe the evolutionary derivation of two hormone receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Both receptors arose from a gene duplication event deep in the vertebrae lineage.
In most vertebrates, GR is used to regulate metabolisms, immunity and inflammation while MR is used by the kidney to regulate electrolyte homeostasis. GR is uniquely specific to the stress hormone cortisol, and is regulated through the binding of cortisol. MR, on the other hand, can interact with both cortisol and another hormone, aldosterone. However, in most MR expressing tissues, a cortisol scavenging mechanism exists to render MR an uniquely aldosterone responsive receptor. The expression of GR and MR is also found in lower vertebrates, such as the skate. In more primitive animals, such as the jawless fish lamprey and hagfish, only a single corticoid receptor (CR) is present. In turn, these animals only produce cortisol, and not aldosterone. All of these receptors are responsive to the intermediary hormone, 11-Deoxycorticosterone (DOC).
The authors of the Science paper, by piecing together the genetic information from the GR and MR isolated from skates and the CR from lamprey and hagfish, "resurrected" the ancestral corticoid receptor (AncCR). The AncCR, surprisingly, is responsive to cortisol and aldosterone, and DOC, much like the vertebrate MR. The authors were able to express AncCR in vitro for ease of study. From working with all three receptor types, the authors were able to conclude that, from the AncCR, two separate single amino acid point mutations must take place to derive the two distinct receptors MR and GR. One of these mutations transformed the AncCR, normally responsive to aldosterone and cortisol, to become insensitive to both hormones but remain responsive to DOC. With this first point mutation in place, the second point mutation resurrects the cortisol binding capabilities of AncCR, transforming it into the vertebrate GR.
Cool huh? It gets better. Aldosterone is only found in vertebrates. However, cortisol and DOC are found in both invertebrates and vertebrates. Aldosterone, however, is only found in vertebrates, yet both aldosterone and cortisol are end point product to progesterone, sharing DOC as an intermediary. So, along with the change in the receptors, a transformation was also happening with hormone regulation and bioavailability. What has not been demonstrated is which came first, the change and transformation of the hormone or the evolution of the receptor.
This gets us back to why i had a good geek laugh today. Perhaps the change of two "piddling" amino acids (each with a 1 in 20 chance of being the correct change) in a 984 amino acid protein isn't "irreducibly complex" in the eyes of Dr. Behe (note: numbers used chosen by author due to laziness in calculating the probability of the occurrence if one were to look at the nucleotide sequence). It certainly is complex enough for a mere bench jockey of my limited capacities. Yes, perhaps a two component system like hormone and receptor interaction is "piddling" in the eyes of mighty Dr. Behe, but for a mere mortal like i, who understands the myriads of different intracellular signaling pathways a single hormone can alter, it is "irreducibly complex" enough. Well, let me take that back. "Irreducibly complex" enough to get my geek w00d up and pit my life and intellect into understanding it, but not "irreducibly complex" enough for me to throw up my hand heavenward and say "ummm... that person did it".
Somewhere in the evolution of the species, a hormone evolutionary step and a receptor evolutionary step took place. This change was but one piece of the whole that led to the divergence between vetebrate and invertebrate species. Enclosed in this story of evolution lies the extreme flexibility and adaptability of biology.
Dr. Behe, the "main advocate of intelligent design", in dismissing the work reported in the article as "piddling" has made my day. i've not had such a hearty geek laugh for so long! Sigh.
The article describes the following paper published in the journal Science. The paper describe the evolutionary derivation of two hormone receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Both receptors arose from a gene duplication event deep in the vertebrae lineage.
In most vertebrates, GR is used to regulate metabolisms, immunity and inflammation while MR is used by the kidney to regulate electrolyte homeostasis. GR is uniquely specific to the stress hormone cortisol, and is regulated through the binding of cortisol. MR, on the other hand, can interact with both cortisol and another hormone, aldosterone. However, in most MR expressing tissues, a cortisol scavenging mechanism exists to render MR an uniquely aldosterone responsive receptor. The expression of GR and MR is also found in lower vertebrates, such as the skate. In more primitive animals, such as the jawless fish lamprey and hagfish, only a single corticoid receptor (CR) is present. In turn, these animals only produce cortisol, and not aldosterone. All of these receptors are responsive to the intermediary hormone, 11-Deoxycorticosterone (DOC).
The authors of the Science paper, by piecing together the genetic information from the GR and MR isolated from skates and the CR from lamprey and hagfish, "resurrected" the ancestral corticoid receptor (AncCR). The AncCR, surprisingly, is responsive to cortisol and aldosterone, and DOC, much like the vertebrate MR. The authors were able to express AncCR in vitro for ease of study. From working with all three receptor types, the authors were able to conclude that, from the AncCR, two separate single amino acid point mutations must take place to derive the two distinct receptors MR and GR. One of these mutations transformed the AncCR, normally responsive to aldosterone and cortisol, to become insensitive to both hormones but remain responsive to DOC. With this first point mutation in place, the second point mutation resurrects the cortisol binding capabilities of AncCR, transforming it into the vertebrate GR.
Cool huh? It gets better. Aldosterone is only found in vertebrates. However, cortisol and DOC are found in both invertebrates and vertebrates. Aldosterone, however, is only found in vertebrates, yet both aldosterone and cortisol are end point product to progesterone, sharing DOC as an intermediary. So, along with the change in the receptors, a transformation was also happening with hormone regulation and bioavailability. What has not been demonstrated is which came first, the change and transformation of the hormone or the evolution of the receptor.
This gets us back to why i had a good geek laugh today. Perhaps the change of two "piddling" amino acids (each with a 1 in 20 chance of being the correct change) in a 984 amino acid protein isn't "irreducibly complex" in the eyes of Dr. Behe (note: numbers used chosen by author due to laziness in calculating the probability of the occurrence if one were to look at the nucleotide sequence). It certainly is complex enough for a mere bench jockey of my limited capacities. Yes, perhaps a two component system like hormone and receptor interaction is "piddling" in the eyes of mighty Dr. Behe, but for a mere mortal like i, who understands the myriads of different intracellular signaling pathways a single hormone can alter, it is "irreducibly complex" enough. Well, let me take that back. "Irreducibly complex" enough to get my geek w00d up and pit my life and intellect into understanding it, but not "irreducibly complex" enough for me to throw up my hand heavenward and say "ummm... that person did it".
Somewhere in the evolution of the species, a hormone evolutionary step and a receptor evolutionary step took place. This change was but one piece of the whole that led to the divergence between vetebrate and invertebrate species. Enclosed in this story of evolution lies the extreme flexibility and adaptability of biology.
No comments:
Post a Comment