Science in Christian Perspective
The recent rapid development of biochemical genetics has given us a better appreciation of the nature of mutations. Along with this insight has come the realization that ordinary mutations are apparently not giving us anything new.1.2.
It has been postulated that a new species could arise without new genes by changing the developmental pattern of rates of action and timing of gene action.3 It seems possible, however, that timing and rates of action are also under the control of specific genes. Inversions and other chromosome rearrangements are factors in isolating populations from interbreeding, so that characteristic allelic differences become established in the separated groups. These differences can be great enough to justify classifying them as separate species; though the two groups still have essentially the same genes. The various modifications of the gene lead to many different alleles or forms. The re sponse of these alleles to such things as suppressors, temperature, irradiation, and growing conditions, can be quite different.
Classical geneticists on getting new phenotypes from their mutants, often thought in terms of new genes as an explanation for them. The study of mutant effects in the bread mold, Neurospora, have shown that mutations apparently do not lead to new enzyme systems, but a modified or defective old one with no change in specifiCity.14 The new phenotypes in Drosophila are probably also due to modified gene action or loss of genes, but not to new genes.The realization that mutants are apparently not new genes leaves open the question of how new genes are formed. Several phenomena have been advanced as sources of new genes. Suppressors were once considered to be new genes.4.5 A second mutation in a defective plant can sometimes enable the plant to grow. Such a second beneficial mutation is called a suppressor because it suppresses the defect of the original mutation. The suppressor of plants requiring pyrimidine for growth, it was thought, might act by taking over the function of the mutant gene. The growth of the plant containing the suppressor was affected by feeding arginine but the wild type and the pyrimidine mutant plants were not affected, so it was not likely that the suppressor was an activated duplicate of the pyrimidine gene.4 Drs. Mitchell and Mitchell no longer make their earlier claim that the suppressor might act by taking over the function of the mutant gene. The pyrimidine suppressor acts on three mutants, pyrimidine 3a, proline 2 & 3, but inhibits seven others. The suppressor may introduce requirements of its own and usually causes a lag in growth so could be considered as a defect mutant, A loss of even one per cent in activity of, the suppressor could reduce the concentration of a biochemical intermediate considerably, and yet not far enough to inhibit normal growth. This drop in concentration could account for the suppressor effect by altering competing enzyme equilibria.6
Suppressors are known to work in at least two ways.
The suppressor of acetate requiring mutants in Neurospora, probably opens up a latent secondary pathway of acetate production, similar to or the same pathway opened up by glycerol as a carbon source. The suppressor is not inhibited by glucose as is glycerol. The suppressor could be removing or reducing the concentration of the glucose metabolite which normally blocks the secondary pathway. Drs. Lein and Lein go on to postulate that many genes exist which do not have an essential function, but which may serve as a pool of gentic material which on mutation makes survival more probable under certain conditions of selection.7 However, the lag in growth response of the wild type plus acetate suppressor suggests that this gene which mutates to a suppressor is essential. Drosophila cannot sustain the loss of any of its genes without a severe mutant effect.8 If Neurospora is at all similar, it Is difficult to imagine where these many non-essential genes could be. Heterochrornatin 'has been suggested as a source of new genetic material.1 It may be essential for nucleic acid metabolism in gene duplication-but does not answer the problem of how this non-specific material can mutate to specific genes, essential for the life of the organism.
The second way suppressors can work is by restoring the synthesis of the lost enzyme system.9 If the destruction of the enzyme were inhibited it would appear the same as an increased synthesis.10 Two allelic or closely linked tryptophane requiring mutants (C-83 & S-1952) are lacking in tryptophane desmolase activity as measured by an assay method capable of detecting one-four hundredth of the wild type enzyme activity. Various temperature, culture and assay conditions were used without eliciting activity. The suppressor will not suppress C-83, for C-83 plus suppressor is still lacking enzyme activity. S-1952 plus suppressor results in one twentieth wild type activity and is stimulated by adding tryptophane. The wild type plus suppressor gives one-third wild type activity and is not stimulated by aiding tryptophane. The suppressor is therefore a defect mutant and has added a requirement of its own, unrelated to the need for trytophane. The S-1952 suppressor enzyme and wild type enzyme have a similar temperature stability, show a similar molar conversion of indole to tryptophane, a similar chemical inhibition, a similar pH maximum, Michaelis constant and energy of activation. The suppressor does not assume the lost gene function because it is ineffective in C-83, and is not an activated 'repeat' at another locus, for the same reason. Radioactive nitrogen studies eliminate the possibility of a secondary metabolic pathway. Nor does the suppressor relieve S-1952 from an inhibitor, because mixing wildtype with S-1952-suppressor does not affect its growth. The suppressor seems to act by providing an essential for enzyme synthesis rather than for enzyme activation.9 This essential could be provided by inhibiting some system competing for it.
The eagerness with which suppressors were once claimed as new genes makes it evident how well it is realized that ordinary mutations are not giving us anything new. Dr. Mather says, "Experimental evidence suffices only to hint at what may be, not to tell what is. All other discussion of Evolution tacitly depends upon the origin of new genes." Ideas of mutations as small unit changes which can be compounded to give discrete orthogenic differences, are no longer valid, if these changes do not result in new genes.
Duplicate gene loci or "repeats" have been suggested as extra genic material from which new genes could arise.11 This is true, but the changes which this material undergoes must be similar to changes at unduplicate gene loci, changes which have never been known to result in a new gene or changed specificity. It is claimed that pseudoalleles might be diverging repeats.12 We have no evidence, however, that duplicate loci can diverge in this manner.13 Dr. E. B. Lewis believes pseudoalleles may be separate genes controlling a series of closely related biochemical functions. Their similarity in function may be due to their control of intermediates they share in common.12
We have considered several phenomena that have been suggested as sources of new genes. In one way or another they are all inadequate, leaving us without a natural explanation for the origin of new genes. Is it not then permissible to consider that the original genes were created by God?
Christians have been criticized for limiting knowledge by ascribing the unknown to God. I am willing to seek natural causes insofar as possible, and I am keeping an open mind toward phenomena not now understood. Logically I object, however, to any attempt at explaining order or design by chance occurrences. Gene action is apparently dependent upon a fairly precise molecular form of the gene, a form which may be distorted by ionizing radiation or other similar agents. This distortion is like noise in an amplifier, in that it obscures the information carried by the gene. Noise itself is not informative, nor can mutations build information into a gene.
It is with real pleasure that I acknowledge the sympathetichelp of Dr. Bernard Phinney and Mrs. Lessie L. Rozier.1. Mather, K. Soc. Exp. Biol. Sym. 7, 66 ('53).
4. Houlahan, M. B. and Mitchell, H. K., Proc. Nat. 4cad. Science. 33, 223 ('47).5. Horowitz, N. H., Adv. Gen. 111, 33 ('50).
6. Mitchell, M. B. and Mitchell, H. K., Proc. Nat. Acad. Science 38, 205 ('52).7. Lein, J. & Lein, P., Proc. Nat. Acad. Science '38, 44 ('52).
Comment by Dr. T. Hinton,
Department of Zoology, U.C.L.A.
think Mr. Sinclair overlooks the main point which
is that if a new function should arise at unduplicated
gene loci, the organism would die since the old gene
has gone and there is nothing to carry on its function,
therefore, one would not expect, a priori, to ever find
them. If, on the other hand, the locus is repeated, one
of the pair is now free to mutate to a new function
while the other one continues to carry on the original
function. This seems perfectly logical until proven
otherwise and certainly does not make it fitting to
relegate new genes to the supernatural. In my opinion,
it is never fitting for a true scientist to deviate from
the natural cause explanation. If some god can create
new genes out of nothing at will, then there is no point
in any of us seeking the basis of life. And as long as
there is any doubt in Mr. Sinclair's mind then he certainly is in the wrong field. His reasoning is very
similar to that of the communists who decided that
since a supernatural force was indicated, genes could
not exist-this is very dangerous reasoning.
The following are a few minor points that bothered me:
1. 1 doubt the validity of the second sentence of the third paragraph. I think that geneticists more frequently think in terms of a new phenotype resulting from the loss of function or a modified function of an old gene rather than resulting from the production of new genes.2. It seems to the that sentence four of the same paragraph should include some phase such as, "or loss of gene or gene function" after the words "reaction rates".
3. The second sentence of paragraph five does not make sense to me.
4. Is the eleventh sentence of paragraph seven rue if C-83 and S-1952 are closely linked genes rather than alleles, a possibility suggested earlier in the paragraph ?
5. The last sentence of paragraph ten makes an awfully big jump. I think something like, "Thus leaving its with the possibility that God is the source of new genes," would be better. I do not think the evidence compels one to turn to God if he does not have the inclination to do so. See Dr. Hinton's comments on this point.
Comment by John C. Sinclair,
Department of Surgery, U.C.L.A.
Dr. Hinton may think I imagine God intervenes in nature in a capricious and unpredictable manner. I am convinced that nature is uniform, not because we have always found it so, but because God is trustworthy, The laws of nature are God's laws.
It is interesting to note that Dr. Hinton expresses the same conclusion that Dr. Mather expressed, that is, that we do not have any experimental evidence for the origin of new genes. This means that we do not have any experimental evidence for the theory of Evolution.
In answer to Dr. Robertson',,; question about the allelism of C-83 and S-1952, let me observe that, what the unit of heredity is, and how best to define it, is still being debated. The two tryptophane requiring mutants satisfy the physiological criteria for identity, but the cross-over criteria is based on whether or not anyone has ever observed crossing-over within the locus under question. Evidence of this sort can never be conclusive. However, C-83 and S-1952 are considered to be allelic by those working with them.