Question 041119a: Are relaxin and insulin (both are proteins) examples that falsify the "protein clock"?

karthaus@photon.chitose.ac.jp

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Answer 041119a: (citation from Schwabe):

"Relaxin is a hormone of vivipary in higher mammals, including man. The 55 % sequence difference between relaxins of man, pig and rat is also often explained by a rapid pace of evolution. Insulins in these species differ very little from each other because functional constraints are purportedly maintaining the structure of this hormone. By the same reasoning, rapid mutation rates are usually postulated to have occurred shortly after gene duplication and before a functional restraint had been acquired. Thus the insulin gene might have duplicated to produce the 'blanc' for a relaxin gene about 200 x 106 years ago and the extra copy might have been mutating rapidly until in placental mammals (70 x 106 years ago) a new function was fixed in position. It is troublesome, however, that shark relaxin is no more different from pig relaxin than pig relaxin is from human relaxin.

Thus, pig relaxin must still have mutated rapidly after a function had been acquired. To make matters worse, it seems quite plausible that the relaxin function might have been fixed already 500 x 106 years ago, at least among viviparous sharks. We have isolated relaxins from Squalus acanthias and Odontaspis taurus and found that these molecules cause widening of the shark birth canal analogous to the mode of action of mammalian relaxin. What seems truly astonishing is that shark relaxin also widens the pelvic bone of mice and guinea pigs; it acts specifically on structures that developed only millions of years later in different species. From this observation it must seem prudent for a molecular evolutionist to conclude that relaxin must have mutated rapidly in spite of functional constraints. Within the paradigm, however, this is considered a quirk which would best be eliminated by arguing that the receptor for relaxin leaves a much greater latitude to the hormone structure than does the receptor for insulin. This explanation loses its plausibility when one recalls that the insulin receptor can also accept variations up to 38 % of the total sequence. More amazing yet is the fact that the insulin of guinea pigs, in violation of the principles of panselectionism, 'devolved' away from the endogeneous receptor to the point where in this species the endogenous insulin is less potent than exogenous porcine insuline. What is the mechanism, we must ask, by which insulin remains nearly constant within one group of the Mammalia whereas another group uses a molecule that differs by roughly 40 % of its sequence? What mechanism is there to explain that the variation between pig and carp or pig and shark is less than the difference between the pig and hystricomorph rodents, and what allows an insulin molecule to change to a less effective state when selection is purportedly improving the fit between hormone and receptor continuously?

It appears that the neo-darwinian hypothesis is insufficient to explain some of the observations that were not available at the time the paradigm took shape. Three of its weaknesses discussed in this paper pertain to the fact that (1) evolutionary trees constructed from different proteins suggest the existence of different genealogies instead of a unique one, (2) genes are much older than previously assumed and (3) panselectionism is not for guinea pigs." (End of Schwabe quote)

Now, this is a real blow to the molecular clock theory and, with it, the whole evolution theory.

Proteins from totally different animals are more similar than closely related ones.

Insulin from pork works better in guinea pigs than guinea pig insulin. Even though guinea pig insulin has evolved in guinea pigs and is supposed the best one (seeQuestion 041118a: survival of the fittest).


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