The genetic code as a clue to understanding of molecular evolution

Sukhodolets, V. V.

doi:10.1016/s0022-5193(89)80120-1

Cited by 5 publications

(4 citation statements)

References 7 publications

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“…1, which suggests that such a kind of close affinity between aa and codons could have a deeper foundation, before time factors evolved that transformed structure units into processes. The stereochemical theory is compatible with other proposals (Sukhodolets, 1989) that a whole unit of aa and RNA preceded the disintegration, implicit also in the numeral series in this study.…”

Section: Discussionsupporting

confidence: 92%

Numeral series hidden in the distribution of atomic mass of amino acids to codon domains in the genetic code

Wohlin¹

2015

Journal of Theoretical Biology

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The distribution of codons in the nearly universal genetic code is a long discussed issue. At the atomic level, the numeral series 2x(2) (x=5-0) lies behind electron shells and orbitals. Numeral series appear in formulas for spectral lines of hydrogen. The question here was if some similar scheme could be found in the genetic code. A table of 24 codons was constructed (synonyms counted as one) for 20 amino acids, four of which have two different codons. An atomic mass analysis was performed, built on common isotopes. It was found that a numeral series 5 to 0 with exponent 2/3 times 10(2) revealed detailed congruency with codon-grouped amino acid side-chains, simultaneously with the division on atom kinds, further with main 3rd base groups, backbone chains and with codon-grouped amino acids in relation to their origin from glycolysis or the citrate cycle. Hence, it is proposed that this series in a dynamic way may have guided the selection of amino acids into codon domains. Series with simpler exponents also showed noteworthy correlations with the atomic mass distribution on main codon domains; especially the 2x(2)-series times a factor 16 appeared as a conceivable underlying level, both for the atomic mass and charge distribution. Furthermore, it was found that atomic mass transformations between numeral systems, possibly interpretable as dimension degree steps, connected the atomic mass of codon bases with codon-grouped amino acids and with the exponent 2/3-series in several astonishing ways. Thus, it is suggested that they may be part of a deeper reference system.

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Section: Discussionsupporting

confidence: 92%

Numeral series hidden in the distribution of atomic mass of amino acids to codon domains in the genetic code

Wohlin¹

2015

Journal of Theoretical Biology

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“…Unlike single nucleotide mutagenesis, which enables the measurement of all possible variants generally accessible during evolution, single amino acid saturation mutagenesis enables measurement of amino acid changes not easily accessible by evolution, i.e., codon changes requiring 2–3 nucleotide changes. We aimed to determine if amino acid changes that resulted from single nucleotide changes were more or less likely to lead to a nonfunctional protein compared with amino acid changes that are only possible following 2–3 adjacent nucleotide changes, consistent with the well-established finding that more similar codons tend to encode more biochemically similar amino acids ( 24 , 25 ). While we observed no difference between the average functional score of amino acid changes caused by single nucleotide changes and those same amino acid changes resulting from multinucleotide changes ( t test, P > 0.05), we observed a strong enrichment of deleterious functional scores among amino acid changes only possible from multinucleotide changes compared with amino acid changes possible from single nucleotide changes (score, –0.18 vs. 0.01, t test, P = 1.4 × 10 –8 ; Figure 6A ) and the average mutational distance of deleterious amino acid changes was significantly greater than that of neutral amino acid changes (2.4 vs. 2.2 nucleotide changes, P = 1 × 10 –58 ; Figure 6B ).…”

Section: Resultsmentioning

confidence: 99%

Comprehensive functional characterization of SGCB coding variants predicts pathogenicity in limb-girdle muscular dystrophy type R4/2E

Li¹,

Wilborn²,

Pittman³

et al. 2023

Journal of Clinical Investigation

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Genetic testing is essential for patients with a suspected hereditary myopathy. More than 50% of patients clinically diagnosed with a myopathy carry a variant of unknown significance in a myopathy gene, often leaving them without a genetic diagnosis. Limb-girdle muscular dystrophy (LGMD) type R4/2E is caused by mutations in β-sarcoglycan ( SGCB ). Together, β-, α-, γ-, and δ-sarcoglycan form a 4-protein transmembrane complex (SGC) that localizes to the sarcolemma. Biallelic loss-of-function mutations in any subunit can lead to LGMD. To provide functional evidence for the pathogenicity of missense variants, we performed deep mutational scanning of SGCB and assessed SGC cell surface localization for all 6,340 possible amino acid changes. Variant functional scores were bimodally distributed and perfectly predicted pathogenicity of known variants. Variants with less severe functional scores more often appeared in patients with slower disease progression, implying a relationship between variant function and disease severity. Amino acid positions intolerant to variation mapped to points of predicted SGC interactions, validated in silico structural models, and enabled accurate prediction of pathogenic variants in other SGC genes. These results will be useful for clinical interpretation of SGCB variants and improving diagnosis of LGMD; we hope they enable wider use of potentially life-saving gene therapy.

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“…The thought that a "whole" have preceded the parts in the genetic code 12 is involved in this analysis as in many others. It is here an analysis in terms of Mass, and since mass as fields were physically accepted with the 'Higg's boson', such whole entities should be more easily imaginable.…”

Section: Discussionmentioning

confidence: 99%

C-skeleton in the genetic code from a basic series 5 → 0, guiding valences and other numeral features in the code

Wohlin¹

2021

MRAJ

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The search for regularities in the background for the genetic code and its codon assignments is here further developed, earlier shown to have many correlations with numeral series of integers 5 →0 with different exponents. The atomic mass analysis here counts on 20 + 4 double-coded amino acids, here including Ile AUA as such. A central finding here is that the C-skeleton seems to build on an hierarchical development of the mentioned basic series giving top numbers equal to those returning in side-chain divisions and on first three levels those of C-atoms in base-pair domains. It can very elementary explain the 3/2-division in the weight series. A few main results from earlier articles are shortly recapitulated, since it’s shown here that an x3-series times 15 (x = integers 5 → 0) joins those earlier aspects and add new ones. It’s found also that atoms with valences 4 + 3 relative those with 2 + 1 make up a 3 to 1-division in both base-pair groups of codon domains, strengthening the earlier observation of valences as one important guiding principle in the relation between codons and domains of amino acids; valences of the atoms which in themselves make up a basic series 5 → 0 in the code when phosphorus P is included. Finally, fundamental factors in the code are gathered, where step 4 →3 seems reign at bottom of the code and number 7, exactly mean value of all atoms.

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The genetic code as a clue to understanding of molecular evolution

Cited by 5 publications

References 7 publications

Numeral series hidden in the distribution of atomic mass of amino acids to codon domains in the genetic code

Numeral series hidden in the distribution of atomic mass of amino acids to codon domains in the genetic code

Comprehensive functional characterization of SGCB coding variants predicts pathogenicity in limb-girdle muscular dystrophy type R4/2E

C-skeleton in the genetic code from a basic series 5 → 0, guiding valences and other numeral features in the code

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