The document discusses the coevolution of humans and plants. It describes how early humans were exposed to a diverse array of phytochemicals from wild plants that provided physiological adaptations. As agriculture developed and the human diet shifted to domesticated plants, exposure to phytochemicals decreased. The document also explores how plant contact may have influenced human neural and language development through synesthesia, and the role of culture in shaping human-plant relationships.

1. Coevolution of Humans and
Plants
Michael Tims, PhD

2. • What do mean by “coevolution of humans and plants”?
• Wild vs. Tame plants
• Human physiological adaptation
• Role of human culture
• Human neural and language development via Synaesthesia

3. Adaptation
A mechanism stimulated by an evolutionary force, where populations
are modified in response to the environment

4. Diversity
• Theory: system diversity proportional to system stability
• Stability of early human health may be related to exposure to
phytochemical diversity

5. Mutations vs. Epigenetics
• Genetic mutations are changes in base pairs.
• Epigenetics is the study of heritable changes in gene activity
that are not caused by changes in the DNA sequence
• Epigenetic changes influence gene expression via altered
methylation and acetylation of a strand of DNA
______________________

6. • Differences between great apes and us not solely from
differences in genes
• Also how they're regulated and if the genes are activated at
different times and strengths
• Cells can regulate the activity of a particular gene by
controlling promoter

7. • Two major kinds of epigenetic modifications
• methylation, methyl group is attached to DNA in specific locations
• histone modification, chemical modifications of scaffolding protein
acting as spool around which DNA is wound
• Methylation can reduce activity of a gene by blocking proteins
from binding to its promoter
• Histone modifications limit accessible to a region of DNA

8. Coevolution
• Two structurally coupled systems
• A pair of organisms act as selective agents for each other.
• Lead to more novel trajectories or adaptations
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• Humans profoundly altered genotype and phenotype of
cultivated plants.
• Constant low levels of allelotropic and psychotropic plant
chemicals in the diet of foraging primates or early humans
would have lead to biochemical adaptations.

10. Complex Systems
• Composed of many parts that interconnect in intricate ways.
• Overall emergent behavior is difficult to predict.
• Complexity theory and chaos theory both attempt to reconcile
the unpredictability of non-linear dynamic systems with a
sense of underlying order and structure.

11. Physiological Complexity
• Complex heart-rate rhythm fluctuations
the norm in health individuals
• Disease marked by less complex
dynamics
• Loss of complexity = loss of information
content
• Less adaptable
Goldberger, AL. (1996) Non-linear dynamics for clinicians: chaos theory, fractals and
complexity at the bedside. Lancet. 347: 1312-1314.

12. Wild vs. Tame Food
• Chemistry as communication – information to other organisms
• Early humans exposed to 80,000 to 220,000 phytochemicals in
their diet
• Now – 10,000 phytochemicals

13. Changing Plant Secondary Metabolites
• Agriculture developed 6,000-8,000 years ago (Diamond 2002)
• Record of 2500 domesticated plants with reduced secondary
metabolites (Zeven and de Witt, 1982), (Meyer et al., 2012)
• ↓ flavor
• ↓ pigments
• ↓ toxicity
• ↓ herbivore resistance (Chen et al., 2015)

14. • Cranberry and Brassica genus provide domestication gradient
(Rodriguez-Saona et al., 2011, Benrey et al., 1998)
• Isothiocyanates (Brassicaceae/cabbage family) concentrations greater in
wild populations (Kushad et al., 2004)
• Brocoli isothiocyanates potent Phase 2 enzyme inducer and blocks
mammary tumor formation (Talalay et al., 1995)
• Ancestral wild plant alkaloids levels higher than domesticated
crops (Watson, 1983)

15. Physiological Results of Co-Evolution
• Population patterns of cytochrome P-450 2A6 and 2D6 activity
reflects evolutionary selection pressures of exposure to
xenobiotics. (Sullivan et al., 2008)
• Coevolution of plant based alkaloid neurotoxins and
mammalian xenobiotic-metabolizing CYP enzymes not unique
to humans. (Rat Genome Sequencing Project Consortium, 2004)

16. Early Human Foraging Lead to
Biochemical Adaptations
• Constant low levels of plant mutagens in the diet may have
affected mutation rates or genetic drift.
• Dietary immune modulators may have influenced mortality
rates (adversely or advantageously).
• Psychoactive plants for endurance (stimulants), to enhance
cognitive functions and visual acuity.

17. Primates and Vitamin C
• Once humans stopped foraging and relied on cultivated plants,
complex biochemical pathways become dormant in response
to the multitude of plant compounds

18. Estrogen Rich Plants
• These plants were chosen for domestication
• Potential to influence ovulation cycle

19. Hypothalamic–Pituitary–Adrenal Axis
• Promote healthy regulation of hormones (Mattson et al., 2007)
• Enhance neuroplasticity (McCarty, 2004)
• Mitigate chronic diseases by activating adaptive stress response
signaling (Trewavas and Stewart, 2003, Mattson and Cheng, 2006)

20. • Cumulative measure of
dysregulation
• Impacts both brain and the
physical body
• Encompasses mediators of
adaptation such as cortisol,
the autonomic nervous
system, metabolic hormones
and immune system
mediators
McEwen, B.S. & Seeman, T.S. (1998). Protective and Damaging Effects of Stress Mediators. New England Journal of Medicine, 338, 171-179.
Karlamangla, A. S., et al. (2002). Allostatic load as a predictor of functional decline MacArthur studies of successful aging. Journal of Clinical
Epidemiology, 55, 695-710.
Adapted
Maladapted
Allostatic Load

21. Hormesis
Mattson and Calabrese (2010)
• Biphasic dose-response curve
• Low dose phytochemicals
increase resistance to injury and
disease.
• resveratrol (red wine)
• sulphorane (cruciferous)
• curcumin (turmeric)
• catechins (tea, cocoa)
• allicin (garlic)
Murugaiyah and Mattson, (2015)

22. Example of Hormesis: Schisandria
chinensis
• Lower concentrations stimulates CYP34A enzyme activity
• Lower concentrations inhibit CYP34A mRNA expression
• Higher concentrations reduces activity
• Higher concentration induces CYP34A mRNA expression

23. Plant Contact Influenced by Culture
• Dietary preference - a central part of how cultures are defined.
• According to Daniel Moerman, native American Indians used
plants in a 5:1 ratio as medicine and food.

24. Biocultural Evolutionary Ecology
• Cultural evolution of human societies led to complex
civilizations, based on transmission of written information
• Overtook biological evolution as the primary determinant of
human progress and impact on the planet
• Examples: Human/plant diads
• Green tea and proline rich proteins (PRPs)

25. Human-plant-parasite Triads, Evidence
for Coevolution
• Sickle cell hemoglobin gene (HbβS) frequency high in West
Africa
• Malaria (Plasmodium falcrum) is hyperendemic.
• HbβS prevents Plasmodium from attaching to the hemoglobin
of red blood cells (RBC)

26. Cassava (Manihot esculenta)
• Originally domesticated in American Tropics
• Important source of dietary carbohydrates
• Cyanogenic glycosides - thiocyanate active

27. Chronic, Low-level Cyanide Exposure
• Development of goiter
• Tropical ataxic neuropathy - nerve-damaging disorder that
renders a person unsteady and uncoordinated.
• Severe cyanide poisoning, particularly during famines, is
associated with outbreaks of a debilitating, irreversible
paralytic disorder and, in some cases, death.

28. Benefit
• Effect structure/function of hemoglobin
• inhibiting sickling
• increasing ability to carry oxygen
• prolonging life of RBC.
• Modifies plasmodium proteins to inhibit parasite
• Requirement for inhibition– consistently high consumption of
cassava.

29. Theory
• Human and parasite exposure to cassava compounds reduces
selective advantage of HbβS and lower sickle cell gene
frequency over time by supplanting Plasmodium retarding
effects of HbβS.

30. The Human Species
• The only species with a complex language?
• This preoccupation with abstract symbols is the
foundation of human culture
• The only species able to store information outside
ourselves and transmit it non-genetically to future
generations

31. Human Hardware
• Human culture, especially language, would not exist
were it not for our extraordinarily complex brain.
• Cortical integration processes and combines multiple
inputs from different senses all at once
= sight, smell, taste, touch, and the
recollection of our previous experiences
Tagliazucchi E. et al. (2016) Large-scale signatures of unconsciousness are consistent
with a departure from critical dynamics. 27 January 2016.DOI:
10.1098/rsif.2015.1027

32. Human Hardware
• Pattern recognition
• Neurolinguistic capabilities
• Associative capacities
• Acute eyesight
• Tactile sensitivity
• Fine motor control

33. Human Language
• During the time it took humans to gain language, bi-pedal
locomotion and tool use, the size of our brain tripled.
• All this happened 100,000 years before the invention of writing.
• A fundamental characteristic of the human linguistic/symbolic
system is the correlation of sound to image.
• What these symbolic, linguistic, and, to some degree, musical
functions have in common is a process called synaesthesia.

34. What is Synaesthesia?
• One can "see sounds," or "hear colors”
• At birth we all experience the process.
• A common occurrence under the influence of hallucinogens.
• We routinely and without awareness, engage in the neurolinguistic
synaesthesia needed to understand language

35. Synaesthesia and Brain Development
• We know that humans have been familiar with the properties
of psychedelic plants for thousands to hundred thousand years
• Suppose this interaction with psychotropic plants, over
millions of years, effected the evolution of our sensory and
cognitive functions, as well as the evolutionary events that
gave humans their extraordinarily complex brains
• Recent psilocybin findings vis-à-vis Depression

36. • Studied reduction of anxiety and depression in cancer patients
• Results from study, and a similar small, controlled trial - 80%
patients experienced clinically significant reductions in both
• Response sustained seven months after the single dose.
• Side effects were minimal.
• Intensity of mystical experience correlated with degree their
depression and anxiety decreased.
Ross, S. et al. (2016) Rapid and sustained symptom reduction following psilocybin
treatment for anxiety and depression in patients with life-threatening cancer: a
randomized controlled trial. Journal of Psychopharmacology. 30(12): 1165 - 1180

37. What Kind of Evidence or Proof Exists?
• In shamanic and ritual ceremonies: the intimate
relationship between sound and visions is recognized and
utilized in virtually all shamanic traditions.

38. Kiyaani, Navaho Peyote Road Man -
Healer
• Guides “prayer meetings”
• Concentrates on the chief peyote to facilitate his dialogue with
nature.
• Peyote is inside the healer and the patient’s system
• Peyote is talking to the healer
“Talking with nature; that’s all it is. Whatever you do, peyote
knows. Nature knows. Whatever is wrong inside here,
nature knows. Where the heart is, this peyote goes in there”