Hominid History, Medicinal Plants and Human Health

Hominid History, Medicinal Plants, and Human Health

Personalized Medicine

• The concept of "personalized medicine" is introduced.
• GlaxoSmithKline invested $300$ million in 23andMe, highlighting the importance of personalized medicine.
• Ancestry percentages from 23andMe are provided, showing diverse origins.

Importance of Biodiversity

• Biodiversity is crucial from plants to people and from the field to the fork.
• Plants exhibit high variability in every aspect.

Hominid History and its Effects

• The lecture will cover hominid history and its effects on the present day.
• Svante Pääbo, from the Max Planck Institute for Evolutionary Anthropology, won the 2022 Nobel Prize in Physiology or Medicine for his work in this field.

Timeline of Hominin Evolution

• A timeline of hominin evolution is presented, showing various species from Australopithecus to Homo sapiens, with key species and timeframes.

Ancient DNA and Our History

• Ancient DNA can provide insights into our history and future health.
• A principal component analysis (PCA) illustrates genetic changes in Britain over time.
• The genetic profile of people in Britain has changed considerably, reflecting a complex migration and admixture history.
• During the Paleolithic and Mesolithic periods, individuals in Britain genetically resembled western hunter-gatherers (WHG).
• During the Neolithic period, the arrival of farming populations dramatically shifted the genetic profile towards Anatolian Neolithic farmers (ANF).
• Beginning in the Chalcolithic period and continuing through the Bronze Age, the genetic profile shifted again towards western steppe herders (WSH) from the Pontic steppes.
• Genetic hypotheses generated using PCA can be formally tested using f-statistics.

Coalescent Theory

• Coalescent theory uses DNA to look into the past.
• The multispecies coalescent model is a valuable paradigm for phylogenomics.

Darwin’s Theory of Evolution

• Darwin's theory of evolution by natural selection is outlined:
  1. Variation exists between individuals.
  2. Variation is partly passed from parents to offspring.
  3. More individuals are produced than the environment can sustain.
  4. Survival and reproduction are tied to variation; favorable variants become more common over time.

Center of Human Origin

• A map is presented to discuss the center of human origin.

Unified Tree Sequence

• A unified tree sequence of $3601$ modern and eight high-coverage ancient human genome sequences is presented.
• Included are three Neanderthal genomes (one over $100,000$ years old), a Denisovan genome ($74,000$ to $82,000$ years old), and four genomes from a nuclear family from the Altai Mountains (about $4,600$ years ago).

Spatio-temporal Dynamics in Human History

• Video S1 shows the estimated geographic locations of ancestors from various projects over time.
• The video represents an edge in the tree sequence of chromosome 20, estimating the time and geographic location of parent and child nodes.

Understanding the Language of DNA

• The lecture transitions to understanding the language of DNA and how many genomes humans have.

Human Genomes

• Humans have three genomes:
  • Two are uniparentally inherited.
  • One is biparentally inherited.
• These include mitochondrial DNA (mtDNA), Y-DNA, and autosomal DNA (nucDNA).

Genome Characteristics

• mtDNA genome:
  • $≤17$ Kbp size.
  • 38 genes.
• Autosomal DNA (nucDNA) genome:
  • $~3,000,000$ Kbp size.
  • >50,000 genes.

What Genomes Tell Us

• Different genomes provide different insights into human history.
• Men tended to explore, spreading their Y-chromosomes geographically.
• Women tended to stay home and have children.
• Predictions:
  1. Human Y-chromosome DNA should show little geographic structure.
  2. Human mtDNA should show more geographic structure.

Y-Chromosomes and History

• Y-chromosomes have moved during history, aiding in dissecting prehistoric migration events.
• Phylogeographic distribution of Y-chromosome haplogroup C supports a single coastal 'Out-of-Africa' route.
• Northward expansion in East Asia started approximately $40,000$ years ago.

mtDNA and Geographic Location

• mtDNA tends to stay in the same place.
• Boundaries in South and Southwest Asia were likely shaped during the initial settlement of Eurasia by modern humans.

Hominid Ancestors and Modern Health

• The lecture transitions to discussing our hominid ancestors and their influence on modern-day health.

Human and Neanderthal Interbreeding

• Humans and Neanderthals interbred for a long time.
• A study identified regions of human ancestry in Neanderthals.
• Neanderthal population sizes were estimated to be about 20% lower than previously thought.
• The possibility of two pulses of gene flow from humans to Neanderthals is proposed.

Bidirectional Gene Flow

• Bidirectional gene flow: Neanderthal DNA affects us, and we affected Neanderthal DNA.
• Modern human-to-Neanderthal admixture causes a local increase in heterozygosity in the Neanderthal genome.
• Neanderthals had a smaller effective population size (Ne) than previously estimated.
• A second wave of modern human-to-Neanderthal gene flow occurred ~$100$ to $120$ thousand years ago (ka).

Genomics and Disease

• Understanding history through genomics is important for understanding disease.

Denisovan Introgression Events

• Multiple Denisovan introgression events occurred in modern humans.
• Evidence suggests that several Denisovan populations were adapted to distinct environments.

Ancient DNA and Human Health

• Ancient DNA has a significant influence on human health in the present.
• Neanderthal-derived DNA plays a significant role in autism susceptibility across major populations in the United States.
• A Neanderthal haplotype confers protection against membranous nephropathy.
• A Neanderthal indel might contribute to prostate cancer risk by regulating PDK1 expression.

Human Genetic Variability

• Human beings are genetically variable, and understanding this variability helps improve human life.
• Large international consortia such as the Human Genome Diversity Project (HGDP) focus on Personalized Medicine.

Deep Learning in Biomedicine

• Deep learning has notable biomedical applications.
• Examples include:
  • Transcription factor binding sites prediction.
  • Promoter-enhancer interaction prediction.
  • Metagenomic classification.
  • Variant calling.
  • Disease risk.
  • De novo drug design.
  • Hospitalization outcome prediction.
  • Epileptic seizure prediction.
  • Medical images analysis.

Importance of Genomic Data

• Intricately associated with the effectivity of applying medicinal plants to human health.
  • Humans are variable.
  • Increasing wealth of genomic data.
  • Informs research.
• Plants are highly variable in every way.

Medicinal Plants and Hominid History

• The lecture transitions to discussing medicinal plants and hominid history.

Interdisciplinary Approach to Medicinal Plants

• A holistic, interdisciplinary approach combining evolutionary ecology, molecular biology/biochemistry, and ethnopharmacology is essential for studying medicinal plants.
• This approach leverages data and methods spanning space, time, and species associated with medicinal plant species evolution, ecology, genomics, and metabolomic trait diversity.
• Medicinal plants and people should be viewed as symbiotic partners that have shaped modern societies, improved human health, and extended human lifespans.

Ancient Plant DNA

• Ancient plant DNA can tell us about human-plant interactions during history.
• High-resolution ancient sedimentary DNA shows that alpine plant diversity is associated with human land use and climate change.

Medicinal Plants and Hominid History

• Medicinal plants are intimately intertwined with hominid history.

Animal Use of Medicinal Plants

• Other animals use medicinal plants as well.
• Terms such as zoopharmacognosy, animal self-medication, kin medication, social medication, transgenerational medication, and allomedication are used to describe these behaviors.

Animal Self-Medication

• Many animal species have created their own pharmacies from ingredients that commonly occur in nature.
• Examples of animals self-medicating include bears, deer, elk, apes, lizards, baboons, fruit flies, macaws, spider monkeys, lemurs and elephants.

Evolution of Herbal Medicine

• The evolution of herbal medicine is examined from behavioral perspectives.
• The use of medicinal herbs by animals and humans has prophylactic effects (reducing the likelihood of illness) and therapeutic effects (treating acute infections and inflammatory conditions).
• The origin of herbal medicine may result from animals and humans learning that specific plant parts are useful or from natural selection for a behavioral predisposition to seek out and use plant parts with particular markers of efficacy.
• An evolutionary model accounts for the continued use of ineffective and effective medicinal herbs as well as the use of medicinal herbs with toxic effects.

Medicinal Plants and Selection

• Medicinal plant use and self-medication are under natural selection in wild populations of animals.
• The lecture questions whether this applies to hominids.

Ethnopharmacology

• Ethnopharmacology is defined as the interdisciplinary scientific exploration of biologically active agents traditionally employed.

Timeline of Hominin Evolution

• A timeline of hominin evolution is shown again, highlighting the Paleolithic Age and Ötzi the iceman.

Ötzi the Iceman

• Ötzi lived between 3350 and 3150 BC.
• Evidence of injuries, ailments, and tattoos includes a brain injury, dental caries, periodontitis, gallbladder stones, a cut wound, healed rib fractures, and intestinal parasites.
• Paleomedicine provides an evolutionary context for medicinal plant use.

Evidence of Pre-Homo Sapiens Medicine Use

• More evidence is accumulating about pre-Homo sapiens medicine use.
• Early uses of medicinal plants were “instinctive” and based upon experience.
• The pharmaceutical industry takes advantage of this behavior.
• In 2019, global spending on pharmaceuticals was US$1.25 trillion.</li> <li>It’s difficult to find evidence of medicinal plants in ancestral human settlements because plant material degrades.</li> </ul> <h4 id="archaeologicalevidence">Archaeological Evidence</h4> <ul> <li>Physical evidence for medicinal treatments throughout history is presented.</li> <li>Neanderthal healthcare was widespread, knowledgeable, and effective in reducing mortality risk.</li> <li>Care for the ill and injured was an adaptive practice.</li> <li>Healthcare may have been a significant factor enabling Neanderthals to occupy a predatory niche.</li> </ul> <h4 id="neanderthalhealthcare">Neanderthal Healthcare</h4> <ul> <li>Shanidar 1 survived for at least a decade with significant disabilities.</li> <li>This care represents good evidence that the motivations for care from others were not premeditated.</li> </ul> <h4 id="medicinalplantsandhumans">Medicinal Plants and Humans</h4> <ul> <li>The lecture transitions to discussing medicinal plants and humans.</li> </ul> <h4 id="originsofmodernhumanancestry">Origins of Modern Human Ancestry</h4> <ul> <li>The origins of modern human ancestry are explored.</li> <li>The worldwide expansion of modern humans occurred between$40$and$60$thousand years ago.</li> </ul> <h4 id="sumerianclayslab">Sumerian Clay Slab</h4> <ul> <li>The oldest written evidence of medicinal plant usage for drug preparation is found on a Sumerian clay slab from Nagpur, approximately$5000$years old, with$12$$ recipes referring to over 250 plants.

Poppy

• Poppy (Papaver sp., Family Papaveraceae):
  • Papaver somniferum - used for morphine
  • Edible seeds
  • Symbol of sleep, peace, and death
• Origins with Sumerian peoples, transferred to EU by the silk road.

Henbane

• Henbane (Hyoscyamus niger):
  • Used in combinations with other plants for psychoactive properties.
  • Endangered species.
  • Used for ailments of the bones, rheumatism, toothache, asthma, cough, nervous diseases, and stomach pain.
  • Also used as analgesic, sedative, and narcotic in some cultures.

Mandrake

• Mandrake (Mandragora sp. and Bryonia alba):
  • All species of Mandragora contain highly biologically active alkaloids, tropane alkaloids in particular.
  • Alkaloids make the plant poisonous via anticholinergic, hallucinogenic, and hypnotic effects.
  • In sufficient quantities, it induces a state of unconsciousness and was used as an anesthetic for surgery in ancient times.

Chinese Book on Roots and Grasses

• Chinese book on roots and grasses “Pen T’Sao (1249 CE)”
  • Written by Shennong (神農), known as the