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Genomic Features: Content Sensors, Nucleotide Skew Plot, Strand Asymmetry, and DNA Methylation

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Abstract

This chapter introduces tools to characterize genomic features and illustrates how a phylogenetic perspective can fundamentally alter one’s conclusion on genomic evolution. The chapter starts by explaining content sensors (e.g., nucleotide, dinucleotide, triplet frequencies, etc.) in contrast to signal sensors (e.g., 5’ and 3’ splice sites, branchpoint sites, SD sequences, anti-SD sequences, Kozak consensus in mammalian mRNAs, sense and stop codons, etc.). Frequently used indices for characterizing genomic content sensors include various word skews, with the simplest being GC skew often used to identify the origin of DNA replication in prokayrotes. Single-origin replication in most bacterial genomes results in strong mutation bias between leading and lagging strands which can be graphically revealed by various skew plots. Confounding these strand biases is the genomic modification by DNA methylation which can have profound effect on genome evolution. Association between CpG deficiency and CpG-specific DNA methylation was challenged previously with two mycoplasma genomes but is restored by a phylogeny-based reanalysis and re-interpretation of the genomic data.

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  1. University of Ottawa CAREG and Biology Department, Ottawa, ON, Canada

    Xuhua Xia

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Postscript

Postscript

“No aphorism is more frequently repeated in connection with field trials, than that we must ask Nature few questions, or ideally, one question at a time. The writer is convinced that this view is wholly mistaken. Nature, he suggests, will respond to a logical and carefully thought-out questionnaire; indeed, if we ask her a single question, she will often refuse to answer until some other topic has been discussed” (Fisher 1926).

Researchers have attacked the methylation hypothesis of CpG deficiency without a phylogeny perspective. Nature gave them a wrong answer and landed them in an undesirable position.

Here comes another story for illustrating the value of thinking broadly. I have previously told a fable of Afandi in which the ancient Islamic sage rode his little donkey around the country teaching people to be wise. The king, craving to be recognized as the wisest, had always been wracking his brain for plots to ambush Afandi intellectually. One day he received the happy news that Afandi had recently suffered from double vision and jumped into action immediately by inviting Afandi to the palace to meet him and his courtiers. Upon Afandi’s arrival, the king greeted him, “Congratulation Afandi! I heard that you have just doubled your fortune. Isn’t it true that, through your wise and penetrating eyes, you now see two wives and two houses of your own? Even the little donkey behind you has now doubled itself in your eyes, isn’t? What a smart way of doubling one’s fortune!” Afandi, realizing that the king was making fun of his double vision, was not pleased, but he replied calmly, among the jeering laughters of the courtiers, “Truly, Your Majesty. At this moment, my eyes are misleading me to think that Your Majesty has four legs.”

Just as researchers attacking the methylation hypothesis landed themselves in an undesirable position, so was the king attacking Afandi. Following Fisher’s sagely advice of thinking broadly may keep us safe from making the same mistake.

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Xia, X. (2018). Genomic Features: Content Sensors, Nucleotide Skew Plot, Strand Asymmetry, and DNA Methylation. In: Bioinformatics and the Cell. Springer, Cham. https://doi.org/10.1007/978-3-319-90684-3_11

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