scholarly journals Mitogenomes Reveal Alternative Initiation Codons and Lineage-Specific Gene Order Conservation in Echinoderms

Author(s):  
Zheng Bin Randolph Quek ◽  
Jia Jin Marc Chang ◽  
Yin Cheong Aden Ip ◽  
Yong Kit Samuel Chan ◽  
Danwei Huang

Abstract The mitochondrial genetic code is much more varied than the standard genetic code. The invertebrate mitochondrial code, for instance, comprises six initiation codons, including five alternative start codons. However, only two initiation codons are known in the echinoderm and flatworm mitochondrial code, the canonical ATG and alternative GTG. Here, we analyzed 23 Asteroidea mitogenomes, including ten newly sequenced species and unambiguously identified at least two other start codons, ATT and ATC, both of which also initiate translation of mitochondrial genes in other invertebrates. These findings underscore the diversity of the genetic code and expand upon the suite of initiation codons among echinoderms to avoid erroneous annotations. Our analyses have also uncovered the remarkable conservation of gene order among asteroids, echinoids, and holothuroids, with only an interchange between two gene positions in asteroids over ∼500 Ma of echinoderm evolution.

F1000Research ◽  
2020 ◽  
Vol 8 ◽  
pp. 2072
Author(s):  
Julien Pichon ◽  
Nicholas M. Luscombe ◽  
Charles Plessy

Background: Ascidians, a tunicate class, use a mitochondrial genetic code that is distinct from vertebrates and other invertebrates. Though it has been used to translate the coding sequences from other tunicate species on a case-by-case basis, it is has not been investigated whether this can be done systematically. This is an important because a) some tunicate mitochondrial sequences are currently translated with the invertebrate code by repositories such as NCBI GenBank, and b) uncertainties about the genetic code to use can complicate or introduce errors in phylogenetic studies based on translated mitochondrial protein sequences. Methods: We collected publicly available nucleotide sequences for non-ascidian tunicates including appendicularians such as Oikopleura dioica, translated them using the ascidian mitochondrial code, and built multiple sequence alignments covering all tunicate classes. Results: All tunicates studied here appear to translate AGR codons to glycine instead of serine (invertebrates) or as a stop codon (vertebrates), as initially described in ascidians. Among Oikopleuridae, we suggest further possible changes in the use of the ATA (Ile → Met) and TGA (Trp → Arg) codons. Conclusions: We recommend using the ascidian mitochondrial code in automatic translation pipelines of mitochondrial sequences for all tunicates. Further investigation is required for additional species-specific differences.


F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 2072 ◽  
Author(s):  
Julien Pichon ◽  
Nicholas M. Luscombe ◽  
Charles Plessy

Background: Ascidians, a tunicate class, use a mitochondrial genetic code that is distinct from vertebrates and other invertebrates. Though it has been used to translate the coding sequences from other tunicate species on a case-by-case basis, it is has not been investigated whether this can be done systematically. This is an important because a) some tunicate mitochondrial sequences are currently translated with the invertebrate code by repositories such as NCBI GenBank, and b) uncertainties about the genetic code to use can complicate or introduce errors in phylogenetic studies based on translated mitochondrial protein sequences. Methods: We collected publicly available nucleotide sequences for non-ascidian tunicates including appendicularians such as Oikopleura dioica, translated them using the ascidian mitochondrial code, and built multiple sequence alignments covering all tunicate classes. Results: All tunicates studied here appear to translate AGR codons to glycine instead of serine (invertebrates) or as a stop codon (vertebrates), as initially described in ascidians. Among Oikopleuridae, we suggest further possible changes in the use of the ATA (Ile → Met) and TGA (Trp → Arg) codons. Conclusions: We recommend using the ascidian mitochondrial code in automatic translation pipelines of mitochondrial sequences for all tunicates. Further investigation is required for additional species-specific differences.


2016 ◽  
Vol 14 (3) ◽  
pp. 275-298 ◽  
Author(s):  
Natasa Misic

This paper represents the preliminary results and conclusions on the one of fundamental questions of the genetic code related to the underlying selective mechanisms involved in its origin and evolution, in particular their hypothetical different nature, originally considered in [1,2,3]. A novel approach is introduced, based on known arithmetic regularities inside the genetic code, determined by the nucleon balances of amino acids and their divisibility by the decimal number 37 [4]. As a parameter of the genetic code systematization is introduced an aggregate nucleon number of amino acid and cognate codon, while divisibility test is carried out not only by the number 37, but also by 13.7, the selfsimilarity constant of decimal scaling [5]. Relevant nucleon sums were obtained for the most prominent divisions of the standard genetic code (SGC) according to p-adic model of the vertebrate mitochondrial code (VMC) in [6]. The nucleon number divisibility pattern of 37 and 13.7 for the RNA and DNA codon space, as well as for the amino acid space is also analyzed. The obtained results, particularly a general higher divisibility of the nucleon sums by the numbers 37 and 13.7 in SGC than in VMC, as well as a correspondence between the nucleon number divisibility pattern of both the RNA codon space and the amino acid space of SGC, how separately so conjointly, with the code degeneracy pattern, suggest some conclusions: support the hypothesis [1,2,3,7] that the selective driving forces acting during an emergence (an ancient phase) and an evolution (a modern phase) of the genetic code are different, imply the existence of an environmental-dependent stereochemical mechanism throughout the entire period of the genetic code emergence and support a mineral-mediated origin of the genetic code [7,8].


Symmetry ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 388 ◽  
Author(s):  
Marco José ◽  
Gabriel Zamudio

It has long been claimed that the mitochondrial genetic code possesses more symmetries than the Standard Genetic Code (SGC). To test this claim, the symmetrical structure of the SGC is compared with noncanonical genetic codes. We analyzed the symmetries of the graphs of codons and their respective phenotypic graph representation spanned by the RNY (R purines, Y pyrimidines, and N any of them) code, two RNA Extended codes, the SGC, as well as three different mitochondrial genetic codes from yeast, invertebrates, and vertebrates. The symmetry groups of the SGC and their corresponding phenotypic graphs of amino acids expose the evolvability of the SGC. Indeed, the analyzed mitochondrial genetic codes are more symmetrical than the SGC.


2019 ◽  
Vol 11 (10) ◽  
pp. 2992-3007 ◽  
Author(s):  
David Žihala ◽  
Marek Eliáš

Abstract Mitochondria of diverse eukaryotes have evolved various departures from the standard genetic code, but the breadth of possible modifications and their phylogenetic distribution are known only incompletely. Furthermore, it is possible that some codon reassignments in previously sequenced mitogenomes have been missed, resulting in inaccurate protein sequences in databases. Here we show, considering the distribution of codons at conserved amino acid positions in mitogenome-encoded proteins, that mitochondria of the green algal order Sphaeropleales exhibit a diversity of codon reassignments, including previously missed ones and some that are unprecedented in any translation system examined so far, necessitating redefinition of existing translation tables and creating at least seven new ones. We resolve a previous controversy concerning the meaning the UAG codon in Hydrodictyaceae, which beyond any doubt encodes alanine. We further demonstrate that AGG, sometimes together with AGA, encodes alanine instead of arginine in diverse sphaeroplealeans. Further newly detected changes include Arg-to-Met reassignment of the AGG codon and Arg-to-Leu reassignment of the CGG codon in particular species. Analysis of tRNAs specified by sphaeroplealean mitogenomes provides direct support for and molecular underpinning of the proposed reassignments. Furthermore, we point to unique mutations in the mitochondrial release factor mtRF1a that correlate with changes in the use of termination codons in Sphaeropleales, including the two independent stop-to-sense UAG reassignments, the reintroduction of UGA in some Scenedesmaceae, and the sense-to-stop reassignment of UCA widespread in the group. Codon disappearance seems to be the main drive of the dynamic evolution of the mitochondrial genetic code in Sphaeropleales.


2019 ◽  
Author(s):  
Julien Pichon ◽  
Nicholas M. Luscombe ◽  
Charles Plessy

AbstractBackgroundAscidians, a tunicate class, use a mitochondrial genetic code that is distinct from vertebrates and other invertebrates. Though it has been used to translate the coding sequences from other tunicate species on a case-by-case basis, it is has not been investigated whether this can be done systematically. This is an important because a) some tunicate mitochondrial sequences are currently translated with the invertebrate code by repositories such as NCBI’s GenBank, and b) uncertainties about the genetic code to use can complicate or introduce errors in phylogenetic studies based on translated mitochondrial protein sequences.MethodsWe collected publicly available nucleotide sequences for non-ascidian tunicates including appendicularians such as Oikopleura dioica, translated them using the ascidian mitochondrial code, and built multiple sequence alignments covering all tunicate classes.ResultsAll tunicates studied here appear to translate AGR codons to glycine instead of serine (invertebrates) or as a stop codon (vertebrates), as initially described in ascidians. Among Oikopleuridae, we suggest further possible changes in the use of the ATA (Ile → Met) and TGA (Trp → Arg) codons.ConclusionsWe recommend using the ascidian mitochondrial code in automatic translation pipelines of mitochondrial sequences for all tunicates. Further investigation is required for additional species-specific differences.


Author(s):  
Fernanda M Bosada ◽  
Mathilde R Rivaud ◽  
Jae-Sun Uhm ◽  
Sander Verheule ◽  
Karel van Duijvenboden ◽  
...  

Rationale: Atrial Fibrillation (AF) is the most common cardiac arrhythmia diagnosed in clinical practice. Genome-wide association studies have identified AF-associated common variants across 100+ genomic loci, but the mechanism underlying the impact of these variant loci on AF susceptibility in vivo has remained largely undefined. One such variant region, highly associated with AF, is found at 1q24, close to PRRX1, encoding the Paired Related Homeobox 1 transcription factor. Objective: To identify the mechanistic link between the variant region at 1q24 and AF predisposition. Methods and Results: The mouse orthologue of the noncoding variant genomic region (R1A) at 1q24 was deleted using CRISPR genome editing. Among the genes sharing the topologically associated domain with the deleted R1A region (Kifap3, Prrx1, Fmo2, Prrc2c), only the broadly expressed gene Prrx1 was downregulated in mutants, and only in cardiomyocytes. Expression and epigenetic profiling revealed that a cardiomyocyte lineage-specific gene program (Mhrt, Myh6, Rbm20, Tnnt2, Ttn, Ckm) was upregulated in R1A-/- atrial cardiomyocytes, and that Mef2 binding motifs were significantly enriched at differentially accessible chromatin sites. Consistently, Prrx1 suppressed Mef2-activated enhancer activity in HL-1 cells. Mice heterozygous or homozygous for the R1A deletion were susceptible to atrial arrhythmia induction, had atrial conduction slowing and more irregular RR intervals. Isolated R1A-/- mouse left atrial cardiomyocytes showed lower action potential upstroke velocities and sodium current, as well as increased systolic and diastolic calcium concentrations compared to controls. Conclusions: The noncoding AF variant region at 1q24 modulates Prrx1 expression in cardiomyocytes. Cardiomyocyte-specific reduction of Prrx1 expression upon deletion of the noncoding region leads to a profound induction of a cardiac lineage-specific gene program and to propensity for AF. These data indicate that AF-associated variants in humans may exert AF predisposition through reduced PRRX1 expression in cardiomyocytes.


2020 ◽  
Author(s):  
Kuba Nowak ◽  
Paweł Błażej ◽  
Małgorzata Wnetrzak ◽  
Dorota Mackiewicz ◽  
Paweł Mackiewicz

1AbstractReprogramming of the standard genetic code in order to include non-canonical amino acids (ncAAs) opens a new perspective in medicine, industry and biotechnology. There are several methods of engineering the code, which allow us for storing new genetic information in DNA sequences and transmitting it into the protein world. Here, we investigate the problem of optimal genetic code extension from theoretical perspective. We assume that the new coding system should encode both canonical and new ncAAs using 64 classical codons. What is more, the extended genetic code should be robust to point nucleotide mutation and minimize the possibility of reversion from new to old information. In order to do so, we follow graph theory to study the properties of optimal codon sets, which can encode 20 canonical amino acids and stop coding signal. Finally, we describe the set of vacant codons that could be assigned to new amino acids. Moreover, we discuss the optimal number of the newly incorporated ncAAs and also the optimal size of codon blocks that are assigned to ncAAs.


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