Generalised interrelations among mutation rates drive the genomic compliance of Chargaff's second parity rule

Chargaff's second parity rule (PR-2), where the complementary base and k-mer contents are matching within the same strand of a double stranded DNA (dsDNA), is a phenomenon that invited many explanations. The strict compliance of nearly all nuclear dsDNA to PR-2 implies that the explanation shou...

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Main Authors: Pflughaupt, P, Sahakyan, AB
Format: Journal article
Language:English
Published: Oxford University Press 2023
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author Pflughaupt, P
Sahakyan, AB
author_facet Pflughaupt, P
Sahakyan, AB
author_sort Pflughaupt, P
collection OXFORD
description Chargaff's second parity rule (PR-2), where the complementary base and k-mer contents are matching within the same strand of a double stranded DNA (dsDNA), is a phenomenon that invited many explanations. The strict compliance of nearly all nuclear dsDNA to PR-2 implies that the explanation should also be similarly adamant. In this work, we revisited the possibility of mutation rates driving PR-2 compliance. Starting from the assumption-free approach, we constructed kinetic equations for unconstrained simulations. The results were analysed for their PR-2 compliance by employing symbolic regression and machine learning techniques. We arrived to a generalised set of mutation rate interrelations in place in most species that allow for their full PR-2 compliance. Importantly, our constraints explain PR-2 in genomes out of the scope of the prior explanations based on the equilibration under mutation rates with simpler no-strand-bias constraints. We thus reinstate the role of mutation rates in PR-2 through its molecular core, now shown, under our formulation, to be tolerant to previously noted strand biases and incomplete compositional equilibration. We further investigate the time for any genome to reach PR-2, showing that it is generally earlier than the compositional equilibrium, and well within the age of life on Earth.
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spelling oxford-uuid:836c2e14-db80-4a2b-8d91-c2a4e9e803f32024-06-18T20:08:23ZGeneralised interrelations among mutation rates drive the genomic compliance of Chargaff's second parity ruleJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:836c2e14-db80-4a2b-8d91-c2a4e9e803f3EnglishJisc Publications RouterOxford University Press2023Pflughaupt, PSahakyan, ABChargaff's second parity rule (PR-2), where the complementary base and k-mer contents are matching within the same strand of a double stranded DNA (dsDNA), is a phenomenon that invited many explanations. The strict compliance of nearly all nuclear dsDNA to PR-2 implies that the explanation should also be similarly adamant. In this work, we revisited the possibility of mutation rates driving PR-2 compliance. Starting from the assumption-free approach, we constructed kinetic equations for unconstrained simulations. The results were analysed for their PR-2 compliance by employing symbolic regression and machine learning techniques. We arrived to a generalised set of mutation rate interrelations in place in most species that allow for their full PR-2 compliance. Importantly, our constraints explain PR-2 in genomes out of the scope of the prior explanations based on the equilibration under mutation rates with simpler no-strand-bias constraints. We thus reinstate the role of mutation rates in PR-2 through its molecular core, now shown, under our formulation, to be tolerant to previously noted strand biases and incomplete compositional equilibration. We further investigate the time for any genome to reach PR-2, showing that it is generally earlier than the compositional equilibrium, and well within the age of life on Earth.
spellingShingle Pflughaupt, P
Sahakyan, AB
Generalised interrelations among mutation rates drive the genomic compliance of Chargaff's second parity rule
title Generalised interrelations among mutation rates drive the genomic compliance of Chargaff's second parity rule
title_full Generalised interrelations among mutation rates drive the genomic compliance of Chargaff's second parity rule
title_fullStr Generalised interrelations among mutation rates drive the genomic compliance of Chargaff's second parity rule
title_full_unstemmed Generalised interrelations among mutation rates drive the genomic compliance of Chargaff's second parity rule
title_short Generalised interrelations among mutation rates drive the genomic compliance of Chargaff's second parity rule
title_sort generalised interrelations among mutation rates drive the genomic compliance of chargaff s second parity rule
work_keys_str_mv AT pflughauptp generalisedinterrelationsamongmutationratesdrivethegenomiccomplianceofchargaffssecondparityrule
AT sahakyanab generalisedinterrelationsamongmutationratesdrivethegenomiccomplianceofchargaffssecondparityrule