Forsdyke Laboratory of Bioinformatics and Theoretical Biology

 

 

 

Laboratory group circa 1995Recent Collaborators

Research Projects (Bioinformatics-Genomics-Theoretical Biology)

Recent Publications (Bioinformatics-Genomics-Theoretical Biology)

Past Projects (Molecular Biology)

Publications (Molecular Biology)

Forsdyke HomePage (AIDS, Bioinformatics, Evolution, Theoretical Immunology, X Chromosomes)

 

 

 

Keywords: Bioinformatics, Genomics, Theoretical Biology, Speciation, AIDS, Evolution, Biohistory, Darwin, Butler, Romanes, Bateson, Goldschmidt, Chargaff, Wada, G0/G1 switch genes (G0S genes), Immunology, Malaria

 

 

 

Department of Biomedical and Molecular Sciences, Botterell Hall, Queen's University, Kingston, Ontario, Canada, K7L3N6.

Donald Forsdyke

forsdyke@queensu.ca
 
 
Recent Collaborators:
 
Dr. Anthony D. Cristillo Grad. Stud. (1993-97) to NIH (1998-02). Advanced BioScience Laboratories, Maryland, USA (2002- )
Dr. Scott P. Heximer Grad. Stud. (1990-96) to St. Louis, Mo (1997-02). Professor at Dept. Physiol., Univ. Toronto (2003- )
LaVerne Russell Technical assistant (1979-1997) to well earned domesticity (garden, flute, travel and canine care)
Sheldon Bell 1996. Undergraduate student. To software design for Royal Bank of Canada.
Labonnie Biswas 1995. Undergraduate student. To Graduate Studies, U. of Toronto.
Kha Dang 1997. Undergraduate student. To further education
Previn Dutt 1997. Undergraduate student. To Graduate Studies in Biochemistry, Queen's.
Tim Lillicrap 1997 High School student, the University of Toronto and then Graduate Studies at Queen's and Oxford.
Janet Ho 1997. Undergraduate student. Graduate Studies in Biochemistry, Queen's.
Y.C.(Derek) Chow 1997. Undergraduate student. To Dental School.
Isabelle Barrette 1998. Undergrad. student. M.Sc. Bioinformatics U. Montreal, Ph.D. U. Alberta, Assist. Prof. Biology, U. Calgary (2006- )
Sean McKenna 1998 Undergraduate student. Graduate studies at U. of Alberta. Assos. Prof. at Dept. Chemistry, U. Manitoba
David. R. Taylor 1998 Undergraduate student. To Medical School
Perry J. Lao 1999. Undergraduate student. Ottawa Law School graduated 2002. Deceased 2006 after 10K run.
Gregory Hill 1999. Undergraduate student. To start own software company.
Robert Rasile 1999. Undergraduate student. To further education.
James R. Mortimer 2000. Undergraduate student. To bioinformatics with Merck-Frosst.
Theresa M. St. Denis 2000. Undergraduate student. To MJS BioLynx Inc.
Alexander K. Schramm 2000. Undergraduate student. To medical school
Robin Lambros 2000. Undergraduate student. To biotech. industry
Chris Madill 2000-1. Undergraduate student. To Grad. studies at Hosp. for Sick Children, Toronto
Scott. D. Smith 2001. Undergraduate student. To Grad. studies as Hosp. for Sick Children, Toronto
H. Y. (Joanne) Xue 2002. Undergraduate student. To Grad studies at University of Toronto.
 S-J. (Jessica) Lee 2002. Undergraduate student. To Grad studies at U BC and then McGill.
Justin LeBlanc 2003. Undergraduate student. To Grad studies at U BC.
Jonathan Rayment 2004. Undergraduate student. To Grad studies at McGill University and on to medical school.
Feng-Hsu (Nelson) Lin 2005. Undergraduate student. To Grad studies at Queen's University.
Virgil R. Reese 2007- . Independent scholar. Bartlesville, Oklahoma.
Dr. Chiyu Zhang 2008. Jiangsu University School of Medical Technology, Zhenjiang; 2012 to Institut Pasteur of Shanghai, Chinese Academy of Sciences.
Dr. Ji-Fu Wei 2008. The Clinical Experiment Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu. 
 
 
 
Projects (Bioinformatics/Genomics/Theoretical Biology)

  • Self/Not-self discrimination (extracellular and intracellular)
  • Speciation, Haldane's Rule
  • X-chromosome dosage compensation
  • Evolution of genetic dominance
  • Biohistory
  • Folding of randomized-sequence difference analysis
  • Chargaff difference analysis: purine-loading of RNAs
  • Role of CHI sequences in recombination
  • Origin of Introns, "Junk" DNA and low complexity elements
  • Isochores (micro and macro)
  • Conflict between different forms of information in selected genes/genomes:
    • G0S genes
    • MHC genes
    • Retroviruses (HIV, HTLV)
    • Herpes simplex virus
    • Epstein-Barr virus
    • Plasmodium falciparum
    • Saccharomyces cerevisiae (chromosome III)
    • Bithorax complex (Drosophila melanogaster)
    • The nematode worm C. elegans

 
Recent Publications (Bioinformatics/Genomics/Theoretical Biology/Biohistory)

 

Forsdyke, D. R. (2024) Theory in Biosciences  (in press).  Speciation, Natural Selection, and Networks: Three Historians Versus Theoretical Population Geneticists. Social Sciences Research Network. (Click Here)

Forsdyke, D. R. (2023) Scandinavian J. Immunology 97, e13306. Aggregation-prone peptides from within a non-self protein homoaggregate are preferred for MHC association: historical overview.  (Click Here)

Forsdyke, D. R. (2023) Quios Preprint. Cryptic evidence on underreporting of mRNA vaccine induced cardiomyositis in the elderly: a need to modify antihypertensive therapy. (Click Here)

Forsdyke, D. R. (2022) J. Genetics 101 (1), 26. Centenary of Haldane's "rule": why male sterility may be normal, not "idiopathic". (Click Here)

Forsdyke, D. R. (2022) Scandinavian J. Immunology 95, e13144. Positive selection of immune repertoires: a short further history. (Click Here) .

Forsdyke, D. R. (2022) FASEB Journal 36, e22158. When "doping" is OK: the importance not only of basic research, but how it is funded. (Click Here). 

Forsdyke, D. R. (2021) Encyclopedia of Life Sciences 2, 1-11. Functional constraint and molecular evolution. (Click Here)  

Forsdyke, D. R. (2021) Biological Theory 16, 237-241. Complementary oligonucleotides rendered discordant by single base mutations may drive speciation. (Click Here) :
Forsdyke, D. R. (2021) Genetica 149, 81-88 (Click Here). Neutralism versus selectionism: Chargaff's second parity rule revisited. Preprint in Computational Biology eJournal (SSRN) - genomics/genetics. (Click Here)

Zhang, C. & Forsdyke, D. R. (2021) Computational Biology and Chemistry  94, 107570 (Click Here) . Potential Achilles heels of SARS-CoV-2 are best displayed by the base order-dependent component of RNA folding energy. bioRxiv Preprint (2020) Click Here or Here

Forsdyke, D. R. (2020 ) Newsletter of the History of Science Society 49 (3), 29-30. Finding team A? Scientist historians and historians of science. (Click Here).
Forsdyke, D. R. (2020) Scandinavian Journal of Immunology 92, e12929. (Click Here) Metabolic optimization of adoptive T-cell transfer cancer immunotherapy: a historical overview.

Forsdyke, D. R. (2020) arXiv Preprint Server. SARS-CoV-2 mortality in blacks and temperature-sensitivity to an angiotensin-2 receptor blocker. Click Here
Forsdyke, D. R. (2020) Biological Theory 15, 143-147. (Click Here) Classics in Biological Theory. Revisiting George Romanes' "Physiological Selection" 1886.  
Forsdyke, D. R. (2020) Biological Theory 15, 50-55. (Click Here)  Aging, DNA information and authorship: Medawar, Schrodinger and Samuel Butler.

Forsdyke, D. R. (2020) Theory in Biosciences 139, 95-104 (Click Here) When few survive to tell the tale: thymus and gonad as auditioning organs.  arXiv Preprint (Click Here) 

Forsdyke, D. R. (2019) Biological Journal of the Linnean society 128, 779-788. Hybrid sterility can only be primary when acting as a reproductive barrier for sympatric speciation. (Click Here)  arXiv Preprint Click Here
Forsdyke, D. R. (2019) Scandinavian Journal of Immunology  90, e12797. On certain two-signal views on lymphocyte activation and inactivation, thymic G-quadruplexes, and the role of aggregation in self/not-self discrimination. (Click Here)

Forsdyke, D. R. (2019)  Biological Journal of the Linnean society 128, 239-250. Success of alignment-free oligonucleotide (kmer) analysis confirms relative importance of genomes not genes in speciation. (Click Here) arXiv Preprint Click Here

 Forsdyke, D. R. (2019) Scandinavian Journal of Immunology  89, e12746. Two signal half century: from negative selection of self-reactivity to positive selection of near-self reactivity. Click Here
 Forsdyke, D. R. (2019) Science 366, 43. The physicist and the dawn of the double helix. e-Letter comment on K Sigmund. Messengers are not prescient. (Click here for full text)
 Forsdyke, D. R. (2019) Science 364, eaaw2872. Passenger hotspot mutations in cancer driven by APOBEC3A and mesoscale genomic features. e-Letter comment on Buisson et al., Why passenger gene mutations are independent of replication timeing and less subject to positive selection over evolutionary time than driver genes . (Click here for full text) 
Forsdyke, D. R. (2019) Nucleic Acids Research 47, 4970-73. "Why genes in pieces?" - revisited. Comment on Smithers et al., Darryl Reanney's parallel hypothesis on introns. (Click here for full text)
Forsdyke, D. R. (2018) Biological Journal of the Linnean society. 124, 139-150. (Click Here) The chromosomal basis of species initiation: PRDM9 as an Anti-Speciation Gene. BioRxiv Preprint version   (Click Here).

Forsdyke, D. R. (2018) arXiv Preprint Server. Confirmation that T cell receptor activation is digital, not analog. Click Here

Forsdyke, D. R. (2018) Encyclopedia of Life Sciences Mendel, Gregor Johann. Click Here  [doi: 10.1002/9780470015902.a0002544.pub2]

Forsdyke, D. R. (2018) Shift in Nomenclature not Thesis: Innate Immune Memory, Pathogen Dose and Opsonins. arXiv Preprint Server (Click Here) 

Forsdyke, D. R. (2018) Science 360 , 223-226. B cell positive selection. e-Letter comment on Burnett DL et al., Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination. (Click here for full text)
Forsdyke, D. R. (2017) Biological Theory 12 (3) 157-168. Base composition, speciation, and why the mitochondrial barcode precisely classifies. (Click Here)  Preprint version   (Click Here).  
Forsdyke, D. R. (2017) Biological Theory 12 (1), 4-12.  Speciation: Goldschmidt's chromosomal heresy, once supported by Gould and Dawkins, is again reinstated. (Click Here); arXiv Preprint version (Click Here) 
Forsdyke, D. R. (2016) arXiv Preprint server  Elusive preferred hosts or nucleic acid level selection? (Click Here). 
Forsdyke, D. R. (2016) Social Sciences Research Network. William Bateson, black slavery, eugenics and speciation: The relative roles of politics and science. (Click Here) or see (2014) PeerJ PrePrints 2:e294v1 (Early copy Here)
Reese V. R. & Forsdyke, D. R. (2016) Biological Theory 11, 150-157.   Meiotic pairing inadequacies at the levels of X chromosome, gene, or base: Epigenetic tagging for transgenerational error-correction guided by a future homologous duplex.  (Click here)
Forsdyke, D. R. (2016) Microbes & Infection 18 , 450-459. Almroth Wright, opsonins, innate immunity and the lectin pathway of complement activation: a historical perspective.  (Click here)
Forsdyke, D. R. (2015) Biological Theory 10 (4), 336-342. Wittgenstein's certainty is uncertain: Brain scans of cured hydrocephalics challenge cherished assumptions.  (Click here)   
Forsdyke, D. R. (2015) J. Evaluation in Clinical Practice 21 (6) 1024-27. Physician-scientist-patients who barketh not. The quantified self movement and crowd-sourcing research.   (Click here)
Forsdyke, D. R. (2015) History of Psychiatry 26 (3), 270-287.  "A vehicle of symbols and nothing more." George Romanes, theory of mind, information, and Samuel Butler. (Click Here) Earlier version (Click Here) 
Forsdyke, D. R. (2015) BMC Research Notes 8, 227. Summertime dosage-dependent hypersensitivity to an angiotensin II receptor blocker. (Click Here) Earlier Versions: 1 (long), 2 (short), 3 (long) (Click Here)
Forsdyke, D. R. (2015) Immunology and Cell Biology 93, 297-304. Lymphocyte repertoire selection and intracellular self/not-self discrimination: historical overview. (Click Here).  Earlier version arXiv (Click Here)
Forsdyke, D. R. (2015) Genome Biology and Evolution 7, 1519-32. Diminished Role for Conventional Natural Selection. A comment on Brnic, Warnecke, Krisko and Supek: Global shifts in genome and proteome composition are very tightly coupled.For comment find PMID:25971281 (Click Here)
Forsdyke, D. R. (2015) Molecular Biology and Evolution 32, 835-845. Adaptation Decoupled from Speciation. A comment on Hedges et al: The Tree of life reveals clock-like speciation and diversification. For comment find PMID:25739733 (Click Here)
Forsdyke, D. R. (2015) American Naturalist 185, 433-432. Adaptation Decoupled from Speciation. A comment on Rothfels et al.: Natural hybridization between genera that diverged from each other approximately 60 million years ago. For comment find PMID:25674696 (Click Here)

[NOTE:  Because of the PubMed Commons "experiment" (2013-2018; see below and ASBMB Today 2018 6, p.43 Click Here ), many comments were placed there and not here. Links to all (except the first three of the 2015-2018 comments that are shown above with PMID numbers) can be accessed as shown below.]

Forsdyke, D. R. (2014) Lewin's GENES XI (eds.  J. E. Krebs, S. T. Kilpatrick & E. S. Goldstein). Revision of Chapter 4 ("The Interrupted Gene") and Section 6 of Chapter 8 ("How Did Interrupted Genes Evolve?"). Published by Jones & Bartlett, Sudbury, MA. Click Here
Forsdyke, D. R. (2014) Frontiers in Human Neuroscience 8, 397.  Long-term memory. Scaling of information to brain size. doi: 10.3389/fnhum.2014.00397. (Click Here) (Earlier Version Here)  
Forsdyke, D. R. (2014) Microbes and Infection 16, 96-103. Implications of HIV RNA structure for recombination, speciation, and the neutralism-selectionism controversy.  (Click Here). For earlier versions  (Click Here)  (or Here)
Forsdyke, D. R. (2014) Newsletter of the History of Science Society 43 (3), 10-14. Teaching Those Who Teach Evolution: The Khan Academy Approach.  (Click Here). For early version.  Click Here  
Forsdyke, D. R. (2014) Genome Biology and Evolution 7, 336-348. GC Differences Not Caused by Conventional Selection. A comment on Clement, Fustier, Nabholz & Glemin: The Bimodal Distribution of Genic GC Content is Ancestral to Monocot Species. For comment find PMID:25527839 (Click Here)
Forsdyke, D. R. (2014) Biology Direct 9, 29. Continuing support for Grantham's 'Genome Hypothesis.' A comment on Goncearenco & Berezofsky: The Fundamental Tradeoff in Genomes and Proteomes of Prokaryotes Established by the Genetic Code, Codon Entropy, and Physics of Nucleic Acids and Proteins. Click Here 
 Forsdyke, D. R. (2014) PLOS Pathogens 10, no. 4, e1004040 . Latency correlates with base composition similarities between HTLV1 and EBV. A comment on Philip et al.: Regulation of Human T-Lymphotropic Virus Type 1 Latency and Reactivation by HBZ and Rex Folding. (Click Here)
Forsdyke, D. R. (2014) PLOS Biology 12, no. 7, e1001910. DNA structure trumps RNA structure. A comment on Yang, Chen & Zhang: Codon-by-Codon Modulation of Translational Speed and Accuracy Via mRNA Folding. (Click Here)
Forsdyke, D. R. (2014) PLOS Computational Biology 10, no. 5, e1003607. Can nucleic acid function be deemed secondary? A comment on Macossay-Castillo et al.: Synonymous constraint elements show a tendency to encode intrinsically disordered protein segment. (Click Here)
Forsdyke, D. R. (2014) Nature 505, 621-622. Further layers of information at the genome level? A comment on Ramos and Laederich .: Molecular Biology: A Second Layer of Information in RNA. (Click here)
Forsdyke, D.R. (2014) eLife 3, e02504. Hypotheses of species initiation are both genic and non-genic. A comment on Turner and Harr: Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions. (Click Here)   
 Forsdyke, D. R. (2013) Biological Theory 7, 196-203. Introns First. (Click Here) or (Here)
Forsdyke, D. R. (2013) Trends in Ecology and Evolution  28, 73-74.  Base composition, speciation and barcoding. Click Here
Forsdyke, D. R. (2013) PLOS Genetics 9, e1003528. Grantham's genome hypothesis (1980). A comment on Prendergast & Semple : Side effects: substantial non-neutral evolution flanking regulatory sites.  Click Here
Forsdyke, D. R. (2013) PLOS Genetics 9, e1003527. Strong selection at synonymous sites conserves nucleic acid structure. A comment (with reply)on Lawrie, Messer, Hershbert & Petrov : Strong purifying selection at synonymous sites in D. melanogaster.  Click Here
Forsdyke, D. R. (2013) PLOS One 8, e76215. Overnight resting allows lymphocyte recovery from preparative stress. A comment on Kutscher et al.: Overnight resting of PBMC changes functional signatures of antigen specific T- Cell responses.  Click Here
 Forsdyke, D. R. (2012) BioEssays  34, 930-933. Ohno's hypothesis and Muller's paradox: sex chromosome dosage compensation may serve collective gene functions. Click Here
Forsdyke, D. R. (2012) Journal of the History of Biology 45, 139-161.  Immunology (1955-1975): The natural selection theory, the two signal hypothesis, and positive repertoire selection. Click Here or Here
Forsdyke, D. R. (2012) PLOS Pathogens 8, e1003112. Purine-loading as a general immune evasive strategy. A comment on Tellam et al.: Messenger RNA sequence rather than protein sequence determines the level of self-synthesis and antigen presentation of the EBV-encoded, EBNA1.  Click Here
Forsdyke, D. R. (2012) PLOS One 7, e37929. Mode switch of heat shock proteins. A comment on Chafekar & Duennwald: Impaired heat shock response in cells expressing full-length polyglutamine-expanded Huntingtin.  Click Here
Forsdyke, D. R. (2012) PLOS Genetics 8, e1002535. The Bateson-Punnett Reduplication Hypothesis. A comment on James F. Crow : Upsetting the dogma: germline selection in human males.  Click Here
 Forsdyke, D. R. (2012) Biology Direct 7, 11. Another "Introns First" Scenario. A comment on Rogozin, Carmel, Csuros & Koonin : Origin and Evolution of Spliceosomal Introns. Click Here
Forsdyke, D. R. (2012) PLOS One 7, e31150. Purine-loading as an adaptation to temperature. A comment on D. Jollivet et al. : Proteome adaptation to high temperatures in the ectothermal hydrothermal vent Pompei worm.  Click Here
Forsdyke, D. R. (2011) Isis 102, 579-580. Review of Darwin's Disciple. George John Romanes. A Life in Letters. by Joel S. Schwartz (Am. Phil. Soc. 2011).  Click Here
Forsdyke, D. R. (2011) Biological Theory 5, 246-255. The selfish gene revisited: reconciliation of Williams-Dawkins and conventional definitions. Click Here
Forsdyke, D. R. (2011) Heredity 106, 202. The B in BDM. William Bateson did not advocate a genic speciation theory. (letter) Click Here 
Forsdyke, D. R. (2011) BMC Biology 9, 52. The non-coding universe was inferred. A comment on Kester Jarvis & Miranda Robertson : The non-coding universe.  Click Here
Forsdyke, D. R., Zhang, C. & Wei, J.-F. (2010) Journal of Biological Systems  18, 1-16 Chromosomes as interdependent accounting units. The assigned orientation of C. elegans chromosomes minimizes the total W-base Chargaff difference. Click Here or Here
Forsdyke, D. R. (2010) Lewin's GENES X (eds.  J. E. Krebs, S. T. Kilpatrick & E. S. Goldstein). Revision of Chapter 4 ("The Interrupted Gene") and Section 6 of Chapter 8 ("How Did Interrupted Genes Evolve?"). Published by Jones & Bartlett, Sudbury, MA. Click Here
Forsdyke, D. R. (2010) Notes and Records of the Royal Society 64, 139-154 (doi:10.1098/rsnr.2009.0045) George Romanes, William Bateson, and Darwin's "Weak Point." Click Here  or  Here 
Forsdyke, D. R. (2010) PLOS Genetics 6, e1001104. Seismic shift of paradigm in molecular evolution. A comment on Rocha E. P. C. & Feil E. J. : Mutational patterns cannot explain genome composition: are there any neutral sites in the genomes of bacteria? Click Here
Forsdyke, D. R. (2010) PLOS Pathogens 6, e1001151. The EBNA1 gene operates at nucleic acid, not protein, level. A comment on Apcher S, Daskalogiannni C, Manoury B  & Fahraeus R : Epstein-Barr virus-encoded EBNA1 interference with MHC class 1 antigen presentation reveals a close correlation between mRNA translation initiation and antigen presentation. Click Here
Forsdyke, D. R. (2009) PLOS One 4, e7553. Chargaff's second parity rule. A comment on Kong, S.-G., Fan, W.-L., Chen, H.-D., Hsu, Z.-T., Zheng, B., & Lee, H. -C. : Inverse symmetry in complete genomes and whole-genome inverse duplication. Click Here
Forsdyke, D. R. (2009) Biology Direct 4, 32. ImRNA or RNA antibody model?. A comment on Flegel, T. W. : Hypothesis for heritable, anti-viral immunity in crustaceans and insects. Click Here
Forsdyke, D. R. (2009) Immunology and Cell Biology 87, 525-528.  X-chromosome reactivation perturbs intracellular self/not-self discrimination.  Click Here
Forsdyke, D. R. (2009) Journal of Theoretical Biology 258, 156-164. Samuel Butler and human long-term memory. Is the cupboard bare? Click Here
Forsdyke, D. R. (2009) PLOS Genetics 5, e1000321. Higher ordered structure is a genome-wide proclivity. A comment on Kavanough, L. A. & Dietrich, F. S.: Non-coding RNA prediction and verification in Saccharomyces cerevisiae.  Click Here
Forsdyke, D. R. (2009) Theory in Biosciences 128, 157-161. Scherrer and Josts' symposium. The gene concept in 2008.  Click Here doi 10.1007/s12064-009-0071-2
Forsdyke, D. R. (2009) Mendel Newsletter 17, 19-21. The papers of William Bateson and Alan Geoffrey Cock at Queen's University.  Click Here
Zhang, C., Xu, S., Wei, J.-F. & Forsdyke, D. R. (2008) Journal of Theoretical Biology 254, 168-177. Microsatellites that violate Chargaff's second parity rule have base order-dependent asymmetries in the folding energies of complementary DNA strands and may not drive speciation. Click Here
Forsdyke, D. R. (2008) PLOS One 3, e1559. DNA level constraints on sequence evolution. A comment on Warden, C. D., Kim, S.-H., & Yi, S. V.: Predicted functional RNAs within coding regions constrain evolutionary rates of yeast proteins. Click here for full text
Forsdyke, D. R. (2007) BMC Genomics 8, 456. Compositional variation between genes is normal. A comment on Monier, A., Claverie, J.-M. & Ogata, H.: Horizontal gene transfer and nucleotide compositional anomaly in large DNA viruses. Click here for full text
Forsdyke, D. R. (2007) Science 317, 910-914. A false Batesonian meme. comment on Reiseberg, L. H  & Willis, J. H.: Plant speciation. (Click here for full text)
Forsdyke, D. R. (2007) Journal of Theoretical Biology 249, 325-330. Molecular sex: the importance of base composition rather than homology when nucleic acids hybridize. (Click here for full text)
Forsdyke, D. R. (2007) Journal of Theoretical Biology 248, 745-753. Calculation of folding energies of single-stranded nucleic acid sequences: conceptual issues. (Click here for full text)
Forsdyke, D. R. (2007) BMC Bioinformatics 8, 33. DNA secondary structure is greater in introns and extragenic DNA. A comment on Babak, T., Blencowe, B. J. & Hughes, T. R.: Considerations in the identification of functional RNA structural elements in genomic alignments. Click here for full text
Forsdyke, D. R. (2007) PLOS One 2, e325. Implication for origin of species. A comment on Min XJ, Hickey DA: DNA Barcodes Provide a Quick Preview of Mitochondrial Genome Composition. Click here for full text
Forsdyke, D. R. (2007) PLOS One 2, e489. Base composition as recombinational isolator. A comment on Sampath et al.: Global surveillance of emerging influenza virus genotypes by mass spectrometry. Click here for full text
Forsdyke, D. R. (2007) PLOS Computational Biology 3, no. 2, e29. Synonymous sites are not neutral. A comment on Lemey, P., Kosakovsky Pond, S. L., Drummond, A. J., Pybus, O. G., Shapiro, B., et al.: Synonymous substitution rates predict HIV disease progression as a result of underlying replication dynamics. Click here for full text
Forsdyke, D. R. (2007) PLOS Genetics 3, no. 2, e21. Simple sequence divergence is not simple. A comment on Greig, D.: A screen for recessive speciation genes expressed in the gametes of F1 hybrid yeast. Click here for full text
Forsdyke, D. R. (2007) PLOS Computational Biology 3, no. 1, e5. Purine loading as a thermal adaptation. A comment on Zeldovich, K. B., Berezovsky, I. N., Shakhnovich, E. I.: Protein and DNA sequence determinants of thermophilic adaptation. Click here for full text
Forsdyke, D. R. (2007) Journal of Biological Systems 15, 95-108. Positive Darwinian Selection. Does the Comparative Method Rule? (Click here for full text)
Lin, F.-H. & Forsdyke, D. R. (2007) Extremophiles 11, 9-18.  Prokaryotes that grow optimally in acid have purine-poor codons in long open reading frames. (Click here for full text)
Forsdyke, D. R. (2006) Centaurus 48, 133-148. Heredity as Transmission of Information. Butlerian Intelligent Design.  (Click here for full text)
Forsdyke, D. R. (2006) Bioinformatics - unpublished. Positive correlation between compositional symmetries and local recombination rates: a commentary on the Discovery Note of Chen and Zhao. (Click here for full text)
Forsdyke, D. R. (2005) Immunology 114, 142-143. The heat-shock response and intracellular self/not-self discrimination [Abstract + slides]  (Click here for full text)
Forsdyke, D. R. (2005) Immunology Letters 100, 103-106. Altered-self" or "near-self" in the positive selection of lymphocyte repertoires? (Click here for full text)
Rayment, J. H. & Forsdyke, D. R. (2005) Applied Bioinformatics 4, 117-130. Amino acids as placeholders: Base composition pressures on protein length in malaria parasites and prokaryotes. (Click here for full text)
Lee, S.-J., Mortimer, J. R. & Forsdyke, D. R. (2004) Applied Bioinformatics.3, 219-228. Genomic Conflict Settled in Favour of the Species Rather than of the Gene at Extreme GC% Values. (Click here for full text)
Forsdyke, D. R. (2004) Journal of Biological Systems 12, 261-271. Regions of Relative GC% Uniformity are Recombinational Isolators. (Click here for full text) 
Forsdyke, D. R. (2004) J. Theor. Biol. 230, 189-196. Chromosomal Speciation: A Reply. (Click here for full text)
Forsdyke, D. R.(2004)  Historic Kingston 52, 95-103. Grant Allen, George Romanes, Stephen Jay Gould and the evolution establishments of their times. (Click here for full text)
Forsdyke, D. R. & Bell, S. J. (2004)  Applied Bioinformatics 3, 3-8.  Purine-loading, stem-loops, and Chargaff's second parity rule: a discussion of the application of elementary principles to early chemical observations. (Click here for full text)
Forsdyke, D. R. (2003) Journal of Biological Systems 11, 341-350. William Bateson, Richard Goldschmidt, and non-genic modes of speciation. (Click here for full text)
Lambros, R. J., Mortimer, J. R. & Forsdyke, D. R.(2003)  Extremophiles 7, 443-450. Optimum growth temperature and the base composition of open reading frames in prokaryotes.(Click here for full text)
Mortimer, J. R. & Forsdyke, D. R.(2003)  Applied Bioinformatics 2, 47-62.  Comparison of responses by bacteriophage and bacteria to pressures on the base composition of open reading frames. (Click here for full text)
Xue, H. Y. & Forsdyke, D. R. (2003)  Mol. Biochem. Parasitol. 128, 21-32. Low complexity segments in Plasmodium falciparum proteins are primarily nucleic acid level adaptations. (Click here for full text)
Forsdyke, D. R., Madill, C. A., & Smith, S. D. (2002) Trends Immunol. 23, 575-579. Immunity as a function of the unicellular state: implications of emerging genomic data.(Click here for full text)
Forsdyke, D. R. (2002) Trends Parasitol. 18, 411-418. Selective pressures that decrease synonymous mutations in Plasmodium falciparum.(Click here for full text)
Forsdyke, D. R. (2002) Bioinformatics 18, 215-217. Symmetry observations in long nucleotide sequences. (Click here for full text)
Forsdyke, D. R. (2001) J. Theor. Biol. 210, 425-434. Adaptive value of polymorphism in intracellular self/not-self discrimination. (Click here for full text)
Barrette, I. H., McKenna, S., Taylor, D. R. & Forsdyke, D. R. (2001) Gene 270, 181-189.  Introns resolve the conflict between base order-dependent stem-loop potential and the encoding of RNA or Protein: Further evidence from overlapping genes.  (Click here for full text)
Cristillo, A.D., Mortimer, J. R., Barrette,  I. H., Lillicrap, T. P. & Forsdyke, D. R. (2001) J.   Theor. Biol. 208, 475-491. 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.  (Click here for full text)
Forsdyke, D. R. & Mortimer, J. R. (2000) Gene 261, 127-137. Chargaff's legacy. (Click here for full text)
Forsdyke, D. R. (2000) J. Theor. Biol. 204, 443-452. Haldane's rule: hybrid sterility affects the heterogametic sex first because sexual differentiation is on the path to species differentiation. (Click here for full text)
Lao, P. J. & Forsdyke, D. R. (2000a) Genome Res. 10, 228-236.Thermophilic bacteria strictly obey Szybalski's transcription direction rule and politely purine-load RNAs with both adenine and guanine. (Click here for full text)
Lao, P. J. & Forsdyke, D. R. (2000b) Gene 243, 47-57. Crossover hotspot instigator (Chi) sequences in E. coli occupy distinct recombination/transcription islands.(Click here for full text)
Bell, S. J. & Forsdyke, D. R. (1999a) J. Theor. Biol. 197, 51-61. Accounting Units in DNA. (Click here for full text)
Bell, S. J. & Forsdyke, D. R. (1999b) J. Theor. Biol. 197, 63-76. Deviations from Chargaff's second parity rule correlate with direction of transcription. (Click here for full text)
Forsdyke, D. R. (1999a) Cell Stress & Chaperones 4, 205-210. Heat shock proteins as mediators of aggregation-induced "danger" signals: implications of the slow evolutionary fine-tuning of sequences for the antigenicity of cancer cel1. (Click Here for full text)
Forsdyke, D. R. (1999b) J. Theor. Biol. 201, 47-61.  Two levels of information in DNA: Relationship of Romanes' "intrinsic" variability of the reproductive system, and Bateson's "residue", to the species-dependent component of the base composition, (C+G)%. (Click Here for full text)
Forsdyke, D. R. (1999c) Queen's Quarterly.106, no. 1. 112-134. The Origin of Species, Revisited. (Click here for full text)
Bell, S. J., Chow, Y. C., Ho, J. Y. K., and Forsdyke, D. R. (1998) Gene 216, 285-292. Correlation of Chi orientation with transcription indicates a fundamental relationship between recombination and transcription.(Click here for full text)
Dang, K. D., Dutt, P. B., and Forsdyke, D. R. (1998) Biochem. Cell Biol. 76, 129-137. Chargaff differences correlate with transcription direction in the bithorax complex of Drosophila.  (Click Here for full text)   FLYBULLET.GIF (3906 bytes)
Forsdyke, D.R. (1998). J. Theor. Biol. 192, 489-504. An alternative way of thinking about stem-loops in DNA. A case study of the G0S2 gene. (Click here for full text)
Forsdyke, D.R. (1998). (not submitted) Negative base order-dependent stem-loop potential of heat shock protein 70 genes indicates evolutionary selection to avoid mRNA secondary structure. (Click here for full text)
Forsdyke, D.R. (1997). J. Mol. Evol. (unpublished) Neutralism versus selectionism: no correlation between optimum growth temperature and genome G+C content does not refute the selectionist viewpoint. (Click here for full text)
Forsdyke, D. R. (1996a) Immunogenetics 43, 182-189. Stem-loop potential in MHC genes: a new way of evaluating positive Darwinian selection. (Click here for full text)
Forsdyke, D. R. (1996b) J. Theoret. Biol. 178, 405-417. Different biological species "broadcast" their DNAs at different (G+C)% "wavelengths". (Click here for full text)
Forsdyke, D.R. (1995a) J. Biol. Systems. 3, 273-287. Entropy-driven protein self-aggregation as the basis for self/not-self discrimination in the crowded cytosol.(Click here for full text)
Forsdyke, D.R. (1995b) J. Theoret. Biol. 172, 335-345. Fine-tuning of intracellular protein concentrations, a collective protein function involved in aneuploid lethality, sex determination and speciation?(Click here for full text)
Forsdyke, D.R. (1995c) Mol. Biol. Evol. 12, 949-958. A stem-loop "kissing" model for the initiation of recombination and the origin of introns.(Click here for full text)
Forsdyke, D. R. (1995d) Mol. Biol. Evol. 12, 1157-1165.Conservation of stem-loop potential in introns of snake venom phospholipase A2 genes: an application of FORS-D analysis. (Click here for full text)
Forsdyke, D. R. (1995e) J. Mol. Evol. 41, 573-581. Relative roles of primary sequence and (G+C)% in determining the hierarchy of frequencies of complementary trinucleotide pairs in DNAs of different species. (Click here for full text)
Forsdyke, D. R. (1995f) J. Mol. Evol. 41, 582-586.Sense in antisense? (Click here for full text)
Forsdyke, D. R. (1995g) J. Mol. Evol. 41, 1022-1037. Reciprocal relationship between stem-loop potential and substitution density in retroviral quasispecies under positive Darwinian selection. (Click here for full text)
Forsdyke, D. R. (1995h) FASEB.J. 9, 164-166. The origins of the clonal selection theory of immunity as a case study for evaluation in science. (Click here for full text)
Forsdyke, D. R. (1995i) Immunology Today 16, 105. Jerne and positive selection. (Click here for full text)
Forsdyke, D. R. (1994a) J. Theor. Biol. 167, 1-6. The heat-shock response and the molecular basis of genetic dominance. (Click here for full text)
Forsdyke, D. R. (1994b) J. Theor. Biol. 167, 7-12.Relationship of X chromosome dosage compensation to intracellular self/not-self discrimination: a resolution of Muller's paradox? (Click here for full text)  

[FOR EARLIER PAPERS SEE BELOW or go to ResearcherID.com/ORCID/Publons] ClickHere

Past Projects (Molecular Biology)lymphocyte
Peripheral blood mononuclear cells have a high proportion of T lymphocytes arrested in the G0 phase of the cell cycle. The cells appear "resting" or "latent", as are any copies of the HIV genome they might contain. On activation, the cells "awake" as does latent HIV. Thus, mechanisms governing lymphocyte "latency" might also be governing HIV latency.

      After activation by the plant lectin, concanavalin A (Con-A), T lymphocytes enter G1 phase and enlarge, subsequently entering S phase and dividing. A set of human putative G0/G1 switch regulatory genes ("G0S" genes) were identified in our laboratory. The corresponding mRNAs were found to be differentially expressed in human blood lymphocytes shortly after the addition of Con-A. It was anticipated that such mRNAs would correspond to proteins involved in orchestrating either entry into the G1 phase of the cell cycle, or the immediate defence response to a foreign pathogen. Some of the genes have been found to play a general role in signal transmission, e.g. in the central nervous system (Click here).

      The 8 genes selected for detailed analysis were G0S2, G0S3, G0S7, G0S8, G0S9, G0S19, G0S24 and G0S30. G0S2 expression is very sensitive to inhibition by the immunosuppressant, cyclosporin-A, and by TNF-alpha. It specifically inhibits triglyceride lipase and the RNA quadruplex-binding protein, nucleolin, so countering the latter's promotion of proliferation (of importance in certain leukaemias; CML). G0S3 and G0S7 are members of the FOS oncogene family. G0S8 has been renamed RGS2 (regulator of G-protein signalling number 2), although it also reacts with adenyl cyclase, and also with the kinase domain of a protein implicated in Parkinson's Disease. G0S9 is "preB cell colony enhancing factor" (PBEF) and Nicotinamide phosphoribosyl transferase (NAMPT), a key to protein deacylations (e.g. facilitating sirtuin-mediated histone deacylations and secretion of TNF-alpha). G0S19, which we reported in 1985 as a differentially expressed mRNA, corresponds to the chemokine MIP1alpha (or CCL3), the receptor for which (CCR5) is a co-receptor for HIV-1. Resistance to AIDS is correlated with copy numbers of G0S19/CCL3 and related genes, or defects in CCR5. G0S24 by virtue of its binding to AU-rich elements, destabilises HIV-1 RNA and the mRNAs of TNF-alpha and tumor suppressors (LATS2), and may prove important for AIDS therapy (Click Here). G0S30, which we also reported in 1985, corresponds to the murine EGR1 and rat NGF1A genes. These encode a transcription factor that regulates TNF-alpha and cell senescence, is a "gatekeeper" of the p53 tumor suppressor pathway, and is implicated in the selection of auditioning T-lymphocytes in the thymus. Some of the human genes have acquired names originally applied to the rodent homologs.
 

Human G0 Switch Gene

Rodent Homolog

G0S2

 G0S2

G0S3/FOSB

FOSB

G0S7/FOS

FOS/TIS28

G0S8/RGS2

RGS2

G0S9/PBEF/NAMPT/Visfatin

 PBEF/NAMPT/Visfatin

G0S19/CCL3

MIP1-alpha/LD78-alpha/464.1/CCL3

G0S24

TIS11/NUP475/TTP (TrisTetraProlin)

G0S30/EGR1

EGR1/NGFI-A/TIS8/ZIF-268
 
Some Publications (Molecular Biology)
Heximer, S.P., Cristillo, A.D., Russell, L. and Forsdyke, D.R. (1998) DNA Cell Biol.17, 249-263. Expression and Processing of G0/G1 Switch Gene 24 (G0S24/TIS11/TTP/NUP475) RNA in Cultured Human Blood Mononuclear Cells.(Click Here) [G0S24 compared with G0S3, G0S7 and G0S19]
Heximer, S.P., Ernst, B.D., Russell, L., and Forsdyke, D.R. (1998) DNA Cell Biol.17,61-68. The normal copy of the G0S19-associated, CpG island-containing, upstream sequence is downstream of G0S19-2/MIP1alpha with a TRE17 oncogene. (Click Here) [G0S19/CCL3 genes]
Cristillo, A.D., Heximer, S.P., Russell, L., and Forsdyke, D.R. (1997) DNA Cell Biol. 16, 1449-1458. Cyclosporin A Inhibits Early mRNA Expression of G0/G1 Switch Gene 2 (G0S2) in Cultured Human Blood Mononuclear Cells.(Click Here) [G0S2 compared with G0S3, G0S7 and G0S30]
Heximer, S. P., Cristillo, A. D. & Forsdyke, D. R.(1997) DNA Cell Biol. 16, 589-598. Comparison of mRNA expression of genes regulating G-protein signalling (RGS1/IR20/BL34 and RGS2/G0S8) in cultured human lymphocytes. (Click Here)
Heximer, S. P., Cristillo, A. D., Russell, L. & Forsdyke, D. R. (1996) DNA Cell Biol. 15, 1025-1038. Sequence analysis and expression in cultured lymphocytes of the human FOSB gene (G0S3).(Click Here) [FOS/G0S7 and FOSB/G0S3 genes]
Cristillo, A. D., Heximer, S. P. & Forsdyke, D. R. (1996) DNA Cell. Biol. 15, 561-570. A "stealth" approach to inhibition of lymphocyte activation by oligonucleotides complementary to the putative G0/G1 switch regulatory gene G0S30/EGR1/ZFP6. (Click Here)
Wu, H-K., Heng, HHQ., Shi, X-M., Forsdyke, D. R., Tsui, L-C., Mak, T.W., Minden, M. D. & Siderovski, D. P. (1995) Leukaemia 9, 1291- 1298. Differential expression of a basic helix-loop-helix phosphoprotein gene, G0S8, in acute leukaemia and localization to human chromosome 1q31.(Click Here)
Siderovski, D. P., Heximer, S.P. & Forsdyke, D. R. (1994) DNA Cell Biol. 13, 125-147.A human gene encoding a putative basic helix- loop-helix phosphoprotein whose mRNA increases rapidly in cycloheximide-treated blood mononuclear cells. (Click Here)  [G0S08, RGS2] [MOST HIGHLY CITED: (Click Here) ]
Heximer, S.P. & Forsdyke, D.R. (1993) DNA Cell Biol. 12, 73-88. A human putative lymphocyte G0/G1 switch gene homologous to a rodent gene encoding a zinc-binding potential transcription factor. (Click Here) [G0S24, TIS11, TTP, Nup475, Zfp36]
Russell, L. & Forsdyke, D.R. (1993) DNA Cell Biol. 12, 157-175. The third human homolog of a murine gene encoding an inhibitor of stem cell proliferation is truncated and linked to a CpG island-containing upstream sequence. (Click Here)  [G0S19/MIP1alpha/CCL3 chemokine series] 
[EARLIER PAPERS SEE BELOW]

Donald Forsdyke and LaVerne Russell circa 1995

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on AIDS, Bioinformatics, Evolution, Theoretical Immunology, X Chromosomes, 
 
from the 19th century onwards, with Commentary. (Click Here)

 

 

 

Comments on Papers as Recorded in PubMed Commons

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This page was initiated in 1998, and last updated 31 Jan 2024, by D. R. Forsdyke

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