On 2017 Nov 30, Donald Forsdyke commented:

CRISPR SPACERS PROVIDE "JUNK" VLA RNAs

A "peculiarity of human thinking" invokes sad head-shaking in some quarters. It is argued, not only that "the vast majority of low abundant transcripts are simply junk," but also that such junk is "simple" (1). Those led to think that junk DNA serves the organism (i.e. can under some conditions be functional and hence selectively advantageous) are labelled "determinists." They can scarcely be distinguished from "ID believers"! There is no mention of the two-decade-old view that very low abundance transcripts (VLA RNAs) represent an intracellular antibody-like repertoire, for which much evidence has since accumulated (2-4).

For microorganisms, the CRISPR system provided a clear example of the functionality of the transcription of their spacer "junk DNA." Ledford notes that the system "adapts to, and remembers, specific genetic invaders in a similar way to how human antibodies provide long-term immunity after an infection" (5). Just as we have germline cascades of V genes that confer immunological specificity on B and T lymphocytes, so microorganisms have their germline spacers that confer a similar specificity on their RNA populations. However, the functionality of an individual spacer "sense" transcript is only tested when a virus with a specific "antisense" sequence enters the cell. Transcription is conditional. The selective advantage can only emerge when the corresponding pathogen attacks.

Thus, the analytical problem is not so "simple" as showing by experimental DNA deletion that the transcript of a specific eukaryotic gene is functional, or as dismissively postulating a requirement for "unacceptably high birth rates." Deletion of a single human V-region gene could show no selective effect if no corresponding pathogens invaded the body. Even if there were such an invasion, other V-regions would likely be able to compensate for the deletion. Similarly, deleting a segment of "junk" DNA is unlikely to impact survival if some of the wide spectrum of alternative "junk" transcripts can compensate for this defect in the RNA antibody-like repertoire.

1.Sverdlov E (2017) Transcribed junk remains junk if it does not acquire a selected function in evolution. BioEssays doi: 10.1002/bies.201700164. Sverdlov E, 2017

2.Cristillo AD, Mortimer JR, Barrette IH, Lillicrap TP, Forsdyke DR (2001) Double-stranded RNA as a not-self alarm signal: to evade, most viruses purine-load their RNAs, but some (HTLV-1, Epstein-Barr) pyrimidine-load. J Theor Biol 208:475-491. Cristillo AD, 2001

3.Forsdyke DR, Madill CA, Smith SD (2002) Immunity as a function of the unicellular state: implications of emerging genomic data. Trends Immunol 23:575-579. Forsdyke DR, 2002

4.Forsdyke DR (2016) Evolutionary Bioinformatics. 3rd edition. Springer, New York, pp. 279-303.

5.Ledford H (2017) Five big mysteries about CRISPR’s origins. Nature 541:280-282. Ledford H, 2017

On 2017 Nov 30, Donald Forsdyke commented:

CRISPR SPACERS PROVIDE "JUNK" VLA RNAs

A "peculiarity of human thinking" invokes sad head-shaking in some quarters. It is argued, not only that "the vast majority of low abundant transcripts are simply junk," but also that such junk is "simple" (1). Those led to think that junk DNA serves the organism (i.e. can under some conditions be functional and hence selectively advantageous) are labelled "determinists." They can scarcely be distinguished from "ID believers"! There is no mention of the two-decade-old view that very low abundance transcripts (VLA RNAs) represent an intracellular antibody-like repertoire, for which much evidence has since accumulated (2-4).

For microorganisms, the CRISPR system provided a clear example of the functionality of the transcription of their spacer "junk DNA." Ledford notes that the system "adapts to, and remembers, specific genetic invaders in a similar way to how human antibodies provide long-term immunity after an infection" (5). Just as we have germline cascades of V genes that confer immunological specificity on B and T lymphocytes, so microorganisms have their germline spacers that confer a similar specificity on their RNA populations. However, the functionality of an individual spacer "sense" transcript is only tested when a virus with a specific "antisense" sequence enters the cell. Transcription is conditional. The selective advantage can only emerge when the corresponding pathogen attacks.

Thus, the analytical problem is not so "simple" as showing by experimental DNA deletion that the transcript of a specific eukaryotic gene is functional, or as dismissively postulating a requirement for "unacceptably high birth rates." Deletion of a single human V-region gene could show no selective effect if no corresponding pathogens invaded the body. Even if there were such an invasion, other V-regions would likely be able to compensate for the deletion. Similarly, deleting a segment of "junk" DNA is unlikely to impact survival if some of the wide spectrum of alternative "junk" transcripts can compensate for this defect in the RNA antibody-like repertoire.

1.Sverdlov E (2017) Transcribed junk remains junk if it does not acquire a selected function in evolution. BioEssays doi: 10.1002/bies.201700164. Sverdlov E, 2017

2.Cristillo AD, Mortimer JR, Barrette IH, Lillicrap TP, Forsdyke DR (2001) Double-stranded RNA as a not-self alarm signal: to evade, most viruses purine-load their RNAs, but some (HTLV-1, Epstein-Barr) pyrimidine-load. J Theor Biol 208:475-491. Cristillo AD, 2001

3.Forsdyke DR, Madill CA, Smith SD (2002) Immunity as a function of the unicellular state: implications of emerging genomic data. Trends Immunol 23:575-579. Forsdyke DR, 2002

4.Forsdyke DR (2016) Evolutionary Bioinformatics. 3rd edition. Springer, New York, pp. 279-303.

5.Ledford H (2017) Five big mysteries about CRISPR’s origins. Nature 541:280-282. Ledford H, 2017