Forsdyke Laboratory of Bioinformatics and Theoretical Biology 

Scott Heximer, Laverne Russell, Anthony Cristillo, Donald ForsdykeRecent 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, Isochores, Evolution, Biohistory, Darwin,  Butler, Romanes, Bateson, Goldschmidt, Chargaff, Wada, G0/G1 switch genes (G0S genes), Immunology, Malaria

Department of Biochemistry, Botterell Hall, Queen's University, Kingston, Ontario, Canada, K7L3N6.

Donald Forsdyke 613-533-2980

forsdyke@post.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). Assist. Prof. at Department of Physiology, 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
Janet Ho 1997. Undergraduate student. Graduate Studies in Biochemistry, Queen's.
Y.C.(Derek) Chow 1997. Undergraduate student. To Dental School.
Isabelle Barrette 1998. Undergraduate student. M.Sc. Bioinformatics U. Montreal. Ph.D. U. of Alberta. Assist. Prof. Biology, U. Calgary (2006- )
Sean McKenna 1998 Undergraduate student. Graduate studies at U. of Alberta.
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 Molecular Mining Inc., Kingston and then 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.
Justin LeBlanc 2003. Undergraduate student. To Grad studies at U BC.
Jonathan Rayment 2004. Undergraduate student. To Grad studies at McGill University.
Feng-Hsu (Nelson) Lin 2005. Undergraduate student. To Grad studies at Queen's University.
 
 
 
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
    • Kaposi's Sarcoma-associated virus (HHV8)
    • Plasmodium falciparum
    • Vaccinia virus
    • Saccharomyces cerevisiae (chromosome III)
    • Bithorax complex (Drosophila melanogaster) FLYBULLET.GIF (3906 bytes)
 
Recent Publications (Bioinformatics/Genomics/Theoretical Biology)

Forsdyke, D. R. (2007) BMC Bioinformatics 8, 33. DNA secondary structure is greater in introns and extragenic DNA. A response to Babak, T., Blencowe, B. J. & Hughes, T. R.: Considerations in the identification of functional RNA structural elements in genomic alignments.
Forsdyke, D. R. (2007) PLOS One 2, e325. Implication for origin of species. A response to Min XJ, Hickey DA: DNA Barcodes Provide a Quick Preview of Mitochondrial Genome Composition.
Forsdyke, D. R. (2007) PLOS Computational Biology 3, no. 2, e29. Synonymous sites are not neutral. A response to 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.
Forsdyke, D. R. (2007) PLOS Genetics 3, no. 2, e21. Simple sequence divergence is not simple. A response to Greig, D.: A screen for recessive speciation genes expressed in the gametes of F1 hybrid yeast.
Forsdyke, D. R. (2007) PLOS Computational Biology 3, no. 1, e5. Purine loading as a thermal adaptation. A response to Zeldovich, K. B., Berezovsky, I. N., Shakhnovich, E. I.: Protein and DNA sequence determinants of thermophilic adaptation. 
Forsdyke, D. R. (2007) J. 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) J. 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) J. 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. 21, 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.  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. (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. (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]
Past Projects (Molecular Biology)
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 transmisssion, e.g. in the central nervous system.

     The 8 genes selected for detailed analysis were G0S2, G0S3, G0S7, G0S8, G0S9, G0S19, G0S24 and G0S30. G0S2 is very sensitive to the immunosuppressant, cyclosporin-A. 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. G0S19, which we reported in 1985 as a differentially expressed mRNA, corresponds to the chemokine MIP1alpha (or CCL3L1), the receptor for which (CCR5) is a co-receptor for HIV-1. Resistance to AIDS is correlated with CCL3L1 gene copy number. G0S24 by virtue of its binding to AU-rich elements, destabilises HIV-1 RNA and tumor necrosis factor alpha (TNFalpha) mRNA, and thus may prove important for AIDS therapy (Click Here). G0S30, which we also reported in 1985, corresponds to the later reported murine EGR1 and rat NGF1A genes. These encode a transcription factor that regulates TNFalpha and cell senescence, and is a "gatekeeper" of the p53 tumor suppressor pathway. Some of the human genes have acquired names originally applied to the rodent homologs.

 

Human G0 Switch Gene

Rodent Homolog

G0S2

.

G0S3/FOSB

FOSB

G0S7/FOS

FOS/TIS28

G0S8/RGS2

RGS2

G0S9/PBEF

.

G0S19/MIP1-alpha/CCL3L1

MIP1-alpha/LD78-alpha/464.1/CCL3L1

G0S24

TIS11/NUP475/TTP

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)

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)

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)

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)

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)

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)

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)  [FOR EARLIER PAPERS SEE BELOW]


HomePage
with Full Text of Selected Papers
,
 
on AIDS, Bioinformatics, Evolution, Theoretical Immunology, X Chromosomes, from the 19th century onwards, with Commentary. (Click Here)

 
COS Profile of DRF  Click Here            Earlier Papers Click Here

This page was initiated in 1998, and last updated 12 Apr 2007, by D. R. Forsdyke


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