Introduction to the Origin of Life 2023 Lecture 1 PDF

Why Cell Biology? György Vereb, February 2023. We are all made up of about 37 trillion cells of 200 different types  As a physician, we need to understand what we work with Anatomy MEDICINE Cell biology Chemistry Bioc...

Why Cell Biology? György Vereb, February 2023. We are all made up of about 37 trillion cells of 200 different types  As a physician, we need to understand what we work with Anatomy MEDICINE Cell biology Chemistry Biochemistry Biophysics Pathology Genetics, molecular biology Histology Physiology  Cells as the basic unit of life Living organisms are single cells or composed of cells Atypical occurrance: striated muscle, giant algae  info History of Cell Biology 1595 – ((Jansen)): first light microscope 1655 – Hooke: ‘cells’ in cork 1674 – Leuwenhoek: observed protista (animalcules) 1833 – Brown: described the cell’s nucleus from the orchid 1839 – Schleiden & Schwann: proposed cell theory (all organisms are comprised of cells) 1857 – Pasteur: discovery of lactobacillus (bacteria are also cells) 1858 – Rudolf Virchow: omnis cellula e cellula - cells develop only from pre-existing cells by a process called cell division 1859 – Darwin: The origin of species (1839!) – evolution theory 1866 – Mendel: Father of Genetics 1874 – Flemming: described chromosome behaviour during mitosis. 1882 – Koch: discovers mycobacterium tuberculosis, establish pathogenic role of bacteria 1894 – Altmann: first described mitochondria. 1898 – Golgi: described the Golgi apparatus. …. …. Cell culturing, Biophysical and Molecular biology tools for observation and manipulation …………………  „The 8th day of creation” 1951, HeLa Science 2010:329 52-56 Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome Evolution and basic properties of the cell  Modern Cell Theory ! All known living things are made up of cells that are their structural & functional units. All cells come from pre-existing cells by division (spontaneous generation does not occur). Cells contain hereditary information which is passed from cell to cell during cell division. Cells are similar in chemical composition. Cells maintain their organized structure by investing energy. Energy producing and energy draining catabolic and anabolic processes happen inside cells.  Origins and main features of life Miller experiment ! compartmentalisation info coded in DNA (genotype) (main) flow of information: DNA→RNA→protein universal genetic code ribosomes “phenotype” determined primarily by proteins In most general terms life involves a system of enzyme catalyzed anabolic and catabolic processes with the ability of self-reproduction. RNA molecules can function as enzymes (ribozymes): RNA polymerase, splicing, polypeptide synthesis, even reverese trasncriptase – thus the RNA world probably preceded the protein world. By coupling the systems of RNA and protein synthesis– via the aminoacyl-tRNA synthetases – the universial genetic code evolved. Science 2007; 318. 62 – 64. Life with Oxygen September 2009 Scientific American; The Origin of Life on Earth eLife. 2017; 6: e32330. Transitioning to DNA genomes in an RNA world  Usually… Prokaryotes (arche- and eubacteria) Eukaryotes unicellular: protists, yeast ! multicellular: plants, animals -nucleoid -nucleus (RNA and protein synthesis separated*) -nucleolus -histons DNA: DNA: -circular, 0.75-5 Mbp -linear, 15 Mbp- -usually no introns -introns in genes* -1 chromosome, membrane-attached -several chromosomes, nucleoskeleton- anchored  usually Prokaryotes Eukaryotes ! -no inner compartmentalization. -mitochondrium, chloroplasts, ER, -no cytoskeleton Golgi, lysosomes, peroxisomes lack of memrbane-bound orfanale -μtubules, μfilaments, intermedier filaments -no endocytosis, exocytosis - endocytosis, exocytosis metabolism: aerob/anaerob -usually aerobic usually unicellular -usually multicellular → differentiation  Characteristic cell biological differences between prokaryotes and eukaryotes ! Prokaryotes Eukaryotes Nucleus only nucleoid Yes Introns No Yes Transcription, translation In one compartment In separate compartments Intracellular membrane systems No Yes (ER, Golgi) Mitochondria No Yes Phagocytosis No Yes Linear (rather than circular) No Yes chromosomes, with telomers Centrioles/centrosome or PCM No Yes Cell fusion (syngamy) No Yes 2 or more cells combine to forma a single cell  Bacteria-like organelles in eukaryotes - Endosymbiotic theory ! http://evolution.berkele y.edu/evolibrary/article /history_24 Mitochondria are thought to have descended from close relatives of typhus-causing bacteria. (cilia? – spirochetes???) Lynn Margulis https://www.discovermagazine.com/the-sciences/discover- interview-lynn-margulis-says-shes-not-controversial-shes-right  Endosymbiosis ! Classical definition: During evolution, a eukaryotic organism, already equipped with adequate cytoskeleton and internal membrane systems for this purpose, engulfed/phagocytosed a prokaryotic organism and they started to live together for their mutual benefit. Mitochondria came about when an aerobic prokaryote performing oxidative phosphorylation was internalized, chloroplasts derived from prokaryotes performing photosynthesys. The origin of peroxysomes is probably similar. Definition which allows more for recent research insitghts: During evolution, an organism (perhaps an archea), already equipped with adequate cytoskeletal and membrane elements for this purpose engulfed a prokaryotic organism and they started to live together for their mutual benefit. Mitochondria came about when an aerobic prokaryote performing oxidative phosphorylation was internalized, chloroplasts derived from prokaryotes performing photosynthesys. The origin of peroxysomes is probably similar.  Evolution of life forms nucleus mitochondrion RNA cell with nucleus and endomembrane system prokaryotes (ancestral eukaryote) Billion yrs ago mutations + selection + endosymbiosis ! Changes in leaps Earth: 4.5 billion*yrs life arises on earth: 3.5-4 billion yrs Pro/eukaryotes: 3 billion yrs Plants, animals, yeasts: 1.5 billion yrs * billion=109 (short scale!)  Main features of the evolution of life on Earth: prebiological evolution → “organic soup”; RNA → DNA catalyzed chemical reactions, trigger principle, cascade principle, feed-back regulation, linked reactions mutability and selection propagation of traits: self-reproductive capacity E. coli divides every 20-40 mins Regulated mutation rate mutations are buffered by other proteins compartmentalization changes in leaps: phagocytic capacity, splicing, sex metabolism: anaerobic > aerobic, ATP Cells Need to Have Large Surface Area-to-Volume Ratio ! (limits size)  Cell functions: ! self-maintenance, housekeeping motility determined growth, proliferation by gene cell-cell communication expression differentiation, morphogenesis How many genes code a cell: Genome size (bp): ! mycoplasma : ~ 300 E. coli: ~ 4000 ~5 million Yeast: ~ 6000 ~12 million C. elegans: ~ 20000 ~100 million Human: ≥ 20000 ~3000 million  Gene expression Prokaryotes Eukaryotes ! DNA cytosol nucleus transcription introns exons mRNA DNA translation protein gene transcription primary RNA* processing 5’ Cap 3’ polyA tail AAAAA Splicing mRNA export mRNA translation protein *primary RNA transcript: pre-RNA, hnRNA  ! How can we have more proteins than genes? – Alternative splicing!  Why do humans have 30x more DNA and about the same info number of genes as C. elegans? Levels of gene expression lncRNAs regulation in (long non- eukaryotes: coding RNA) protein factors and RNAs miRNAs (micro RNA) + circular RNAs  Keywords ! arche- and eubacteria genotype prokaryotes, eukaryotes phenotype Escherichia coli Caenorabditis elegans metabolism protist (protozoa) anabolic, catabolic yeast heterotrophic cell culture Phagocytosis autotrophic endosymbiosis (in evolution) anaerobic, aerobic exon, intron, splicing photosynthesis transcription, translation ribosomes chemosynthesis glycolysis oxidative phosphorylation  Questions you should be able to answer ! Do plants have mitochondria? Which organelle(s) had originated by endosymbiosis? Do bacteria have ribosomes? How many genes code for an E. coli bacterium? What are introns and exons?  REVISION You are expected to know the size range (order of magnitude) of various relevant organic entities, which should be familiar from previous studies You are expected to know the approximate volume, time, speed and concentration ranges of various biologically relevant items/processes  Cell size info cell membrane: 4-10 nm, average protein: 3-6 nm, water molecule: 0.3 nm Basic quantitative features of cell biological relevance info info  Important dimensions in cell biology size (linear) Concentration ! Water molecule 0.3 nm 1 molecule in E. coliban 1 nM DNA diameter 2 nm 1 molecule in a HeLa cell 1 pM Average protein 3-6 nm Average water content 70 % Cell membrane 7 nm Proteins in a cell 3 mM virus (HIV) 100 nm Small metabolites in a cell 300 mM Bacteriophage (T4) 225 nm Mitochondrion 1-5 µm Time bacterium (E. coli) 1-5 µm prot. diffusion across bacterium 10 ms green algae 5-6 µm molecular motor covers 1 µm 1 s Chloroplast 2-10 µm prot. diffusion across HeLa cell 10 s Yeast 3-6 µm E. coli division cycle 20-40 min Red blood cell 7.2 µm Yeast division cycle 70-140 min Average cell 10-20 µm neuron cell body (spread out) 70 µm HeLa cell cycle 15-30 h Neurite (axon)