Optimization of the standard genetic code in terms of two mutation types: Point mutations and frameshifts

Wnętrzak, Małgorzata; Błażej, Paweł; Mackiewicz, Paweł

doi:10.1016/j.biosystems.2019.04.012

Cited by 26 publications

(16 citation statements)

References 62 publications

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“…This shows that the significance of frameshift stability of certain physicochemical properties may be intrinsically connected to the specific architecture of the UGC. Finally, our findings are in general agreement with previous studies on the topic (19,20), although those were limited to just a few specific scales. In contrast, we present a comprehensive analysis of the full scale space providing the necessary context for understanding frameshift stability.…”

Section: Resultssupporting

confidence: 92%

“…It has already been suggested that compositionally similar codons encode amino acids with similar physicochemical properties (16)(17)(18), implying that the UGC may have been optimized for robustness against not only point mutations, but frameshifts as well. However, previous investigations of frameshift stability were performed primarily at the UGC level and only considered few amino acid properties or their indirect correlates, as in the case of substitution matrices (19)(20)(21). In contrast, our present results are based on a comprehensive analysis of over 600 different aminoacid properties and report on the impact of frameshifts in the case of biologically realistic sequences in multiple organisms.…”

Section: Discussionmentioning

confidence: 94%

“…In a related context, it has long been known that similar codons encode amino acids with related physicochemical properties (16)(17)(18). Although the impact of this feature of the universal genetic code (UGC) has been well appreciated in the case of point mutations, its influence in the case of frameshifts has only recently been addressed (19)(20)(21). In particular, Wang et al (21) showed that wild-type sequences and their frameshifted variants exhibit higher than expected similarity as captured by several classic substitution matrices in sequence alignment with gaps.…”

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confidence: 99%

“…Furthermore, Geyer and Madany Mamlouk (19) analyzed a particular physicochemical property of amino acids (i.e., a measure of their partitioning in pyridine/water mixtures) and demonstrated a weak, but significant correlation between frameshifted counterparts at the UGC level. Finally, Wnȩtrzak et al (20) showed that UGC may have been optimized in part to lessen the impact of frameshift mutations. Importantly, however, all of these studies analyzed a limited set of amino acid properties or substitution frequencies only and focused primarily on the UGC.…”

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confidence: 99%

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Frameshifting preserves key physicochemical properties of proteins

Bartonek

Braun

Žagrović

2020

Proc. Natl. Acad. Sci. U.S.A.

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Frameshifts in protein coding sequences are widely perceived as resulting in either nonfunctional or even deleterious protein products. Indeed, frameshifts typically lead to markedly altered protein sequences and premature stop codons. By analyzing complete proteomes from all three domains of life, we demonstrate that, in contrast, several key physicochemical properties of protein sequences exhibit significant robustness against +1 and −1 frameshifts. In particular, we show that hydrophobicity profiles of many protein sequences remain largely invariant upon frameshifting. For example, over 2,900 human proteins exhibit a Pearson's correlation coefficient R between the hydrophobicity profiles of the original and the +1-frameshifted variants greater than 0.7, despite an average sequence identity between the two of only 6.5% in this group. We observe a similar effect for protein sequence profiles of affinity for certain nucleobases as well as protein sequence profiles of intrinsic disorder. Finally, analysis of significance and optimality demonstrates that frameshift stability is embedded in the structure of the universal genetic code and may have contributed to shaping it. Our results suggest that frameshifting may be a powerful evolutionary mechanism for creating new proteins with vastly different sequences, yet similar physicochemical properties to the proteins from which they originate. frameshift | hydrophobicity | genetic code | evolution

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Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Frameshifting preserves key physicochemical properties of proteins

Bartonek

Braun

Žagrović

2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Moreover, Geyer and Mamlouk recently showed that the polarity of the amino acids obtained by frameshifting correlates weakly, but significantly with the polarity of the original amino acids and that this may be an integral property of the genetic code (22). Finally, Wnetrzak and coworkers showed that the genetic code may have been optimized in part to lessen the impact of frameshift mutations (23). Importantly, however, all of these studies analyzed a limited set of amino-acid property scales only, focused exclusively on the genetic code and did not investigate the impact of frameshifting on realistic biological sequences.…”

Section: Introductionmentioning

confidence: 99%

Invariants of Frameshifted Variants

Bartonek

Braun

Žagrović

2019

Preprint

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Frameshifts in protein coding sequences are widely perceived as resulting in either non-functional or even deleterious protein products. Indeed, frameshifts typically lead to markedly altered protein sequences and premature stop codons. By analyzing complete proteomes from all three domains of life, we demonstrate that, in contrast, several key physicochemical properties of protein sequences exhibit significant robustness against +1 and −1 frameshifts in their mRNA coding sequences. In particular, we show that hydrophobicity profiles of many protein sequences remain largely invariant upon frameshifting. For example, over 2900 human proteins exhibit a Pearson correlation coefficient between the hydrophobicity profiles of the original and the +1-frameshifted variants greater than 0.7, despite a median sequence identity between the two of only 6.5% in this group. We observe a similar effect for protein sequence profiles of affinity for certain nucleobases, their matching with the cognate mRNA nucleobase-density profiles as well as protein sequence profiles of intrinsic disorder. Finally, we show that frameshift invariance is directly embedded in the structure of the universal genetic code and may have contributed to shaping it. Our results suggest that frameshifting may be a powerful evolutionary mechanism for creating new proteins with vastly different sequences, yet similar physicochemical properties to the proteins they originate from.Significance StatementGenetic information stored in DNA is transcribed to messenger RNAs and then read in the process of translation to produce proteins. A frameshift in the reading frame at any stage of the process typically results in a significantly different protein sequence being produced and is generally assumed to be a source of detrimental errors that biological systems need to control. Here, we show that several essential properties of many protein sequences, such as their hydrophobicity profiles, remain largely unchanged upon frameshifts. This finding suggests that frameshifting could be an effective evolutionary strategy for generating novel protein sequences, which retain the functionally relevant physicochemical properties of the sequences they derive from.

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Why Is AUG the Start Codon?

Demongeot

Seligmann

2020

BioEssays

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The rational design of theoretical minimal RNA rings predetermines AUG as the universal start codon. This design maximizes coded amino acid diversity over minimal sequence length, defining in silico theoretical minimal RNA rings, candidate ancestral genes. RNA rings code for 21 amino acids and a stop codon after three consecutive translation rounds, and form a degradation‐delaying stem‐loop hairpin. Twenty‐five RNA rings match these constraints, ten start with the universal initiation codon AUG. No first codon bias exists among remaining RNA rings. RNA ring design predetermines AUG as initiation codon. This is the only explanation yet for AUG as start codon. RNA ring design determines additional RNA ring gene‐ and tRNA‐like properties described previously, because it presumably mimics constraints on life's primordial RNAs.

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Optimization of the standard genetic code in terms of two mutation types: Point mutations and frameshifts

Cited by 26 publications

References 62 publications

Frameshifting preserves key physicochemical properties of proteins

Frameshifting preserves key physicochemical properties of proteins

Invariants of Frameshifted Variants

Why Is AUG the Start Codon?

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