Chargaffs second parity rule lies at the origin of additive genetic interactions in quantitative traits to make omnigenic selection possible
Matkarimov B.T. Saparbaev M.K.
2023PeerJ Inc.
PeerJ
2023#11
Background. Francis Cricks central dogma provides a residue-by-residue mechanistic explanation of the flow of genetic information in living systems. However, this principle may not be sufficient for explaining how random mutations cause continuous variation of quantitative highly polygenic complex traits. Chargaffs second parity rule (CSPR), also referred to as intrastrand DNA symmetry, defined as near-exact equalities G ~ C and A ~ T within a single DNA strand, is a statistical property of cellular genomes. The phenomenon of intrastrand DNA symmetry was discovered more than 50 years ago; at present, it remains unclear what its biological role is, what the mechanisms are that force cellular genomes to comply strictly with CSPR, and why genomes of certain noncellular organisms have broken intrastrand DNA symmetry. The present work is aimed at studying a possible link between intrastrand DNA symmetry and the origin of genetic interactions in quantitative traits. Methods. Computational analysis of single-nucleotide polymorphisms in human and mouse populations and of nucleotide composition biases at different codon positions in bacterial and human proteomes. Results. The analysis of mutation spectra inferred from single-nucleotide polymorphisms observed in murine and human populations revealed near-exact equalities of numbers of reverse complementary mutations, indicating that random genetic variations obey CSPR. Furthermore, nucleotide compositions of coding sequences proved to be statistically interwoven via CSPR because pyrimidine bias at the 3rd codon position compensates purine bias at the 1st and 2nd positions. Conclusions. According to Fishers infinitesimal model, we propose that accumulation of reverse complementary mutations results in a continuous phenotypic variation due to small additive effects of statistically interwoven genetic variations. Therefore, additive genetic interactions can be inferred as a statistical entanglement of nucleotide compositions of separate genetic loci. CSPR challenges the neutral theory of molecular evolution-because all random mutations participate in variation of a trait-and provides an alternative solution to Haldanes dilemma by making a gene function diffuse. We propose that CSPR is symmetry of Fishers infinitesimal model and that genetic information can be transferred in an implicit contactless manner.
Chargaffs second parity rule , Continous trait variation , Infinitesimal model , Integral characteristics , Intra-strand DNA symmetry , Nucleotide composition bias , Quantitative trait , Random mutations , Single nucleotide polymorphisms , Statistical entanglement
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National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
L.N.Gumilev Eurasian National University, Astana, Kazakhstan
Groupe Mechanisms of DNA Repair and Carcinogenesis, CNRS UMR9019, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France
Al-Farabi Kazakh National University, Almaty, Kazakhstan
National Laboratory Astana
L.N.Gumilev Eurasian National University
Groupe Mechanisms of DNA Repair and Carcinogenesis
Al-Farabi Kazakh National University
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