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Self/Not-Self?

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Evolutionary Bioinformatics

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Abstract

The full understanding of the genome of a biological species requires an understanding of the genomes of the species with which it has coevolved, which include pathogenic species. Members of a pathogenic species that enter the bodies of members of a host species must be recognized as “not-self” so activating host immunological defenses. However, the capacity of its genomic information channel being limited, a host whose defenses are poised to attack “near-self” versions of not-self (a narrow repertoire), rather than not-self per se (a repertoire formidable in range), should be at a selective advantage. It is likely that immune systems of multicellular organisms are adaptations of those of unicellular organisms, which had already developed the capacity for self/not-self discrimination. From this perspective we can comprehend phenomena such as “junk” DNA, genetic polymorphism and the ubiquity of repetitive elements. That which is evolutionarily conserved is often functional, but that which is functional is not necessarily conserved. Variation itself may be functional. The “hidden transcriptome,” revealed by run-on transcription of genes or repetitive elements constitutes a diverse repertoire of inherited RNA ‘immune receptors’ with the potential to form double-stranded RNA with viral RNA ‘antigens,’ so triggering intracellular alarms. Both genic and non-genic DNA would have been screened over evolutionary time (by selection of individuals in which favorable mutations had been collected together by recombination) to decrease the probability of two complementary “self” transcripts interacting to form dsRNA segments above a critical length (about two helical turns). Thus, many RNAs are purine-loaded. The CRISPR system provides an analogous RNA immune receptor defence in microorganisms. Here numerical differences in CHI sequences and replication forks may facilitate self/not-self discrimination.

Thrice is he armed that hath his quarrel just,

But four times he who got his blow in fust.

Josh Billings, His Sayings (1866) [1]

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  1. Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada

    Donald R. Forsdyke

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Forsdyke, D.R. (2016). Self/Not-Self?. In: Evolutionary Bioinformatics. Springer, Cham. https://doi.org/10.1007/978-3-319-28755-3_15

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