Back to Normal: Natural Reverse Mutations

Yesterday we saw Robert E. Pruitt's discovery of how plants are able to Mend their Own Inherited Faulty DNA, now we will gather some links related to the well known natural reversal to normal, the "reverse mutations":

Thomas Hunt Morgan et al declared (Ref. 1, pp. 169-170): "we know that mutations and even "reverse" mutations actually occur". Since then, others have done additional discoveries in humans on this novel area of prospective medicine (2). Those examples of natural "reverse mutations" (3-5) are leading to the discovery of possible artificial treatments (6-8). And well, the precise mechanisms of such mutational reversion are still been studied (9-10). Other possibility is the use of palindromes in the attachment of two different genetic modules for the engineering of terapeutic proteins.

References:

1. Morgan TH, Sturtevant AH, Muller HJ & Bridges CB (1915). Multiple Allelomorphs. In: (same Authors), The Mechanism of Mendelian Heredity. Henry Holt and Company. New York.

2. Hirschhorn R (2003) In vivo reversion to normal of inherited mutations in humans. J. Med. Genet. 40: 721-728.

3. Wahn V, Stephan V, Hirschhorn R. Reverse mutations-- spontaneous amelioration or cure of inherited disorders? Eur J Pediatr. 1998 Aug;157(8):613-7.

"Some recent publications indicate that inherited disorders can ameliorate or possibly disappear if mutations responsible for the disease revert to normal. This review tries to summarize our current knowledge about reverse mutations as this information may be of special interest for attempts at somatic gene therapy."

4. Gross M, Hanenberg H, Lobitz S, Friedl R, Herterich S, Dietrich R, Gruhn B, Schindler D & Hoehn H (2002) Reverse mosaicism in Fanconi anaemia: natural gene therapy via molecular self-correction. Cytogenet. Genome Res. 98: 126–35.

5. Brown WT, Houck GE Jr, Ding X, Zhong N, Nolin S, Glicksman A, Dobkin C, Jenkins EC. Reverse mutations in the fragile X syndrome. Am J Med Genet. 1996 Aug 9;64(2):287-92.

"inherited a fragile X chromosome from their premutation carrier mothers, and yet had normal size FMR1 repeat alleles... Our results indicate that women identified to be carriers by linkage should be retested by direct DNA analysis."

6. Hacein-Bey-Abina S, Le Deist F, Carlier F, Bouneaud C, Hue C, De Villartay JP, Thrasher AJ, Wulffraat N, Sorensen R, Dupuis-Girod S, Fischer A, Davies EG, Kuis W, Leiva L & Cavazzana-Calvo M (2002) Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N. Engl. J. Med. 346: 1185-93.

7. Gaspar HB, Parsley KL, Howe S, King D, Gilmour KC, Sinclair J, Brouns G, Schmidt M, Von Kalle C, Barington T, Jakobsen MA, Christensen HO, Al Ghonaium A, White HN, Smith JL, Levinsky RJ, Ali RR, Kinnon C & Thrasher AJ (2004) Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector. Lancet 364: 2181-7.

8. O. Adjali, G. Marodon, M. Steinberg, C. Mongellaz, V. Thomas-Vaslin, C. Jacquet, N. Taylor, and D. Klatzmann. In vivo correction of ZAP-70 immunodeficiency by intrathymic gene transfer. J. Clin. Invest., August 1, 2005; 115(8): 2287 - 2295.

9. Bultman SJ, Klebig ML, Michaud EJ, Sweet HO, Davisson MT, Woychik RP. Molecular analysis of reverse mutations from nonagouti (a) to black-and-tan (a(t)) and white-bellied agouti (Aw) reveals alternative forms of agouti transcripts. Genes Dev. 1994 Feb 15;8(4):481-90.

"...we propose that reverse mutations occur by excision of inserted sequences in a through homologous recombination..."

10. English JC, Roser KS, Mecchi M. Conversion of tris(8-quinolinolato-N1, O8) aluminum to 8-hydroxyquinoline and activity in bacterial reverse mutation assays. Mutat Res. 2005 Apr 4;582(1-2):95-104.

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Note:

These are additional findings that demonstrate patterns and non-randomness in such molecular events. Similar findings for the human polymorphisms, in the future will help to therapeutically reverse hereditary diseases.

Earlier, I reported at ARN some other examples in microbes:

"...under leucine starvation conditions, leu+ revertants accumulated as a function of time; leu- to leu+ reverse mutation rates and frequencies were higher than those under non starvation conditions."

"...reverse mutations could occur continuously in a time-dependent manner."

"...reverse mutation under leucine starvation was cell density dependent and growth-dependent."

Taken from an Online Journal: Jianling Jin, Peiji Gao and Yumin Mao. Occurrence of leu+ revertants under starvation cultures in Escherichia coli is growth-dependent. BMC Genetics 2002, 3:6.

And related to the non-randomness, even in mutations (that as we have seen here, can and do revert!):

"Base substitutions and single-base frameshifts, two major classes of spontaneous mutations, occur non-randomly throughout the genome."

Ref.: Hisaji Maki. Origins of Spontaneous Mutations: Specificity and Directionality of Base-Substitution, Frameshift, and Sequence-Substitution Mutageneses. Annual Review of Genetics Vol. 36: 279-303 (Volume publication date December 2002.)

See also:

"...directed variation must be invoked to understand some phenomena, as random variation and selection alone are not a sufficient explanation... The existence of such mechanisms has been predicted by mathematicians."

Ref.: Bernhard, R. 1967. Heresy in the halls of biology: mathematicians question Darwinism. Sci. Res. (New York) 2:59-66.

And also:

"... background mutations are sequence directed and not random in the sense that they occur in bases made vulnerable by virtue of their particular location within specific DNA sequences, such as tandem repeats, or the unpaired and mispaired bases of stem-loop structures"

Taken from: Barbara E. Wright. A Biochemical Mechanism for Nonrandom Mutations and Evolution. Journal of Bacteriology, June 2000, p. 2993-3001, Vol. 182, No. 11.

Again, as in my entry for yesterday, this facts point to the robust Stability of living organisms, designed to endure and to preserve their specified patterns, the integrity of their particular 'kinds' (Heb. Min, Gk. Genos.)