Stop Codons stops NeoDarwinism

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The article "Stop Codon Usage as a Window into Genome Evolution: Mutation, Selection, Biased Gene Conversion and the TAG Paradox" by Ho and Hurst (2023) discusses the factors that influence the usage of the three stop codons (TAA, TGA, and TAG) in different genomes.

Stop codons are the triplets of nucleotides that signal the end of a protein-coding sequence. They are recognized by release factors, which bind to the stop codon and cause the ribosome to release the newly synthesized polypeptide chain.

The three stop codons are not used equally in all genomes. For example, in mammals and birds, TGA is the most common stop codon, while in bacteria, TAA is the most common stop codon.

Ho and Hurst (2023) discuss the three main factors that influence stop codon usage: mutation, selection, and biased gene conversion.

Mutation

Mutation is the random change in the nucleotide sequence of a gene. Mutations can occur in any codon, including stop codons.

The most common type of mutation is a single-nucleotide substitution. This is when one nucleotide is replaced by another.

Single-nucleotide substitutions can convert one stop codon into another. For example, a single-nucleotide substitution can convert a TAA codon into a TGA codon.

Selection

Selection is the process by which organisms with certain traits are more likely to survive and reproduce than organisms without those traits.

Selection can act on stop codon usage in a few ways.

First, natural selection can favor the use of stop codons that are least likely to be read through. Read-through is when the ribosome fails to recognize a stop codon and continues translating the mRNA, resulting in the production of a longer protein.

Second, selection can favor the use of stop codons that are most efficient at terminating translation.

Third, selection can favor the use of stop codons that are compatible with the availability of release factors.

Biased gene conversion

Biased gene conversion is a process by which a DNA sequence is converted to a more similar sequence.

Biased gene conversion can occur between two copies of a gene, or between a gene and a pseudogene. Pseudogenes are non-functional copies of genes that have been lost their ability to code for proteins.

Biased gene conversion can lead to an increase or decrease in the frequency of a particular stop codon.

The TAG paradox

One of the most puzzling observations about stop codon usage is the TAG paradox. The TAG paradox is the fact that TAG is the least common stop codon in most genomes, despite being the most efficient stop codon at terminating translation.

Ho and Hurst (2023) propose that the TAG paradox is due to the methylation (epigenetics) and hypermutability of CpG dinucleotides  CpG dinucleotides are dinucleotides (pairs of nucleotides) that are made up of a cytosine nucleotide followed by a guanine nucleotide.

CpG dinucleotides are methylated in many genomes. Methylation is an epigenetic chemical modification of DNA that can affect gene expression.

Methylated CpG dinucleotides are more likely to mutate than unmethylated CpG dinucleotides. C-M>U>T.

This means that TAG codons, which contain a CpG dinucleotide, are more likely to mutate than TAA or TGA codons, which do not contain a CpG dinucleotide.

Ho and Hurst (2023) conclude that the TAG paradox is best explained by the methylation and hypermutability of CpG dinucleotides.

Conclusion

Stop codon usage is a complex phenomenon that is influenced by a variety of factors, including mutation, selection, and biased gene conversion. The TAG paradox is a particularly puzzling observation about stop codon usage, but Ho and Hurst (2023) propose a plausible explanation for it.


The article by Ho and Hurst (2022) challenges Neo Darwinism in the following ways:

  • It shows that the evolution of stop codon usage is not simply a matter of random mutation and natural selection. Other factors, such as biased gene conversion and DNA methylation, play a significant role.

  • It highlights the importance of G+C content in determining stop codon usage. Neo Darwinism typically focuses on the role of amino acid sequences in determining the fitness of organisms, but this article shows that nucleotide sequences can also play an important role.

  • It raises the possibility that there is an optimal stop codon for each species, and that this codon may not be the same for all species. This is in contrast to the traditional Neodarwinist view that all stop codons are functionally equivalent.

  • It presents the TAG paradox, which is a puzzling observation that is difficult to explain within the framework of Neo Darwinism.

Overall, the article by Ho and Hurst (2022) shows that the evolution of stop codon usage is a complex process that is influenced by a variety of factors. This complexity challenges the traditional Neodarwinist view that evolution is simply a matter of random mutation and natural selection.

Here is a more specific explanation of each of the above points:

Neo Darwinism typically assumes that evolution is driven by random mutation and natural selection. However, the article by Ho and Hurst shows that other factors, such as biased gene conversion and DNA methylation, can also play a significant role in the evolution of stop codon usage. This suggests that evolution is not as random as Neo Darwinism typically assumes.

Neo Darwinism typically focuses on the role of amino acid sequences in determining the fitness of organisms. However, the article by Ho and Hurst shows that nucleotide sequences can also play an important role in determining stop codon usage. This suggests that Neo Darwinism needs to take a broader view of the factors that influence the fitness of organisms.

Traditional Neo Darwinism views all stop codons as functionally equivalent. However, the article by Ho and Hurst raises the possibility that there is an optimal stop codon for each species. This suggests that Neo Darwinism needs to be more nuanced in its understanding of the evolution of stop codon usage.

The TAG paradox is a puzzling observation that is difficult to explain within the framework of Neo Darwinism. It is not clear why TAG is the least common stop codon in most genomes, despite being the most efficient stop codon at terminating translation. This suggests that Neo Darwinism needs to develop new theories to explain the evolution of stop codon usage.

Overall, the article by Ho and Hurst (2022) is a valuable contribution to the study of genome evolution. It challenges Neo Darwinism in a number of ways, and it suggests that new theories are needed to explain the complex evolution of stop codon usage.

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