Summary

These notes provide an overview of model organisms, covering their features, biology, and functions. Topics include characteristics for a useful model organism, details about some common model organisms, and their use in biological studies.

Full Transcript

i. To relate the key features that are required for a model organism to be a valid model for research into humans From the one tree of life we have evidence from molecules, structures and processes, that these things are shared with other organisms, if there is one tree of life and the process...

i. To relate the key features that are required for a model organism to be a valid model for research into humans From the one tree of life we have evidence from molecules, structures and processes, that these things are shared with other organisms, if there is one tree of life and the processes are conserved across the tree of life, we can study something much more simple to get results about humans. Shared molecules, structures and processes means we can study one system to discover general truths. ii. To outline the key requirements for a model organism to be useful as a research model 1. Phenotype of interest is ancestral Similar selection pressure in different taxa, same character derived independently = convergent ovulation cannot be used as a model. 2. The basis of the phenotype is conserved Some traits despite being consistent phenotypes are underpinned by very different mechanistic basis e.g. male and female differentiation across different species Good models Cheap and easy to maintain in large quantities Can create and maintain mutant lines Easy to study trait of interest ( simple and more accessible ) Ethical considerations (pain memory and stress) iii. To describe the natural history background and basic biology of the major model organisms,. Major Models a. Escherichia coli b. Arabidopsis thaliana c. Saccharomyces and Schizosaccharomyces d. Caenorhabditis elegans e. Drosophila Melanogaster f. Danio reriog) Mus musculus Escherichia coli Gamma Proteobacterium isolated from the gut Facultative anaerobe ( can survive with or without oxygen) Very fast growing in optimal conditions (20 minute division time) Related to disease causing strains and species Easy to insert plasmids can engineered plasmids to make proteins Uses a universality of genetic code and protein synthesis systems. Schizosaccharomyces pombe Ascomycete fungus Model unicellular eukaryote Asexual phase repeated cell division Good for studying cell biology and cell division Arabidopsis thaliana Brassicaceae includes important crop plants such as cabbages, broccoli and turnips It is an annual weed species so grows fast and produces seeds very early (fast life cycle) Small genome for a plant well known and completely sequenced (157 Megabases) Genetically manipulable has a knockout of every gene Self fertile, can maintain homozygous lines Can store seeds in a small space Single layer roots easy to study (simplicity) Caenorhabditis elegans Nematode worm roundworm Related to parasitic worms, causing disease in humans and livestock Naturally lives in compost rotting vegetation (bacteriovores) Rapidly develop Hermaphrodite ( self-fertilisation) east to maintain stocks and mutations Can also be crossed, as when stressed produces males Translucent at all life stages easy to visualise changes ( can screen for mutants ) Determinate development 959 cells in adult hermaphrodite Simple neurological system 302 neurons Programmed cell death- Development required both organised cell division and differentiation and organised programmed cell death 1090 cells form, 131 undergo programmed cell death Screen development mutants where process doesn’t happen so can characterise genes and systems Homologous to that in humans Programmed cell death also = vital quality control and cancer defence Neuroscience connectome Small number of neurons ( ï¬​xed type 0 Can map connections animas “wiring diagramâ€​ Examine hermaphrodite vs male differences Gene expression regulation DNA -> RNA -> protein RNAi system small RNa that binds mRNA and targets transcript for destruction = gene expression control system Can express these interfering RNA in E.coli -> feed to C.elegans ->knock down individual gene function Drosophila melanogaster Insect, dipteran (two- winged fly) (fruit fly) Lives on rotting / fermenting fruit and compost heaps. Adult consumes and loves yeast Ethanol tolerant species grows best at 4% EtOH Complete metamorphosis in 10 days on simple banana medium Good model for insect biology related to mosquitoes major vectors of disease Visible polytene chromosomes, so can see chromosomal deletion inversions = genetic trait mapping in era before genomics Inverted “balancerâ€​ chromosomes -> retain recessive deleterious mutations indeï¬​nitely Embryonic development organism form development, from single cell -> complex organism through cell division, death and differentiation Orchestrated by expression of genes that give positional information = Hox genes- Transcription factors deï¬​ne positing therefore alters expression of complex form Innate immunity Antimicrobial system run complimentary to adaptive immunity (antibody based immunity) in vertebrates Main system of immunity in insects ( do not live long enough for immune memory) Pathogen recognition receptors detect surface cell wall molecules of extracellular molecules of microbes (e.g. Peptidoglycan, lipopolysaccharide) Leads to production of broad array of antimicrobial peptides These systems function across plants, vertebrates and invertebrates Danio rerio Freshwater omnivore from SE asia Three month life history Live in groups can keep a large number together Basic vertebrate features heart, pancreas, spinal cord, adaptive immune system External development observable Good embryonic development model, can interfere with gene function on a single cell basis Teratology model ( teratogens substances which cause birth defects ) Fish system for muscular disease shares genetic basis with humans Mouse Mus musculus Small and easy to breed Mammal Wild rodent omnivore living mostly on seeds and fruits Plastic social organisation depends of diet provisioning Relatively close relation to humans Targeted gene knockouts are possibleiv) To relate the key questions those model organisms have been used to answer and areas of research in which they are used. 1. Escherichia coli Bacteria sex, sharing genes between bacteria DNA replication how life copies the genetic code Gene regulation The genetic code Virus replication inside cells Restriction enzymes Recombinant DNA creation of ï¬​rst genetically engineered DNA RNA as an enzyme additional roles ATP generation Signal sequences on proteins GFP Recombinant insulin and Growth hormone Metabolism 2. Arabidopsis thaliana CRISPR Cas9 Plant hormones Metabolic mutants X-ray mutants 3. Saccharomyces and Schizosaccharomyces The cell cycle control of cell division Loss of control of cell division (cancer) over replicating, out of control cell lineages Paul nurses wee mutants Can have large numbers mutagenize and look for focal mutants accelerated cell division mutants appear small Therefore characterised genetic control of the cell cycle (cdc2) Mammalian cdc2 can complement (substitute) for yeast cdc2 4. Caenorhabditis elegans Gene expression- Development Neuroscience 5. Drosophila Melanogaster Chromosomes as linear arrays of genes that segregate (mendelian patterns) Mutational impacts of x-rays Circadian rhythm mechanism Genetic control of early development Innate immunity Innate immunity Antimicrobial system run complimentary to adaptive immunity (antibody based immunity) in vertebrates Main system of immunity in insects ( do not live long enough for immune memory) Pathogen recognition receptors detect surface cell wall molecules of extracellular molecules of microbes (e.g. Peptidoglycan, lipopolysaccharide) Leads to production of broad array of antimicrobial peptides These systems function across plants, vertebrates and invertebrates 6. Danio rerio Vertebrate development immunity, common vertebrate organ system s 7. Mus musculus Circulation of the blood Respiration and vital gases Coat colour Lethal mutations and genetic diseases RNA vaccines Cystic ï¬​brosis ( mutations in CFTR gene [affects chloride transport] )- Cancer obesity Diseases of ageing v. To describe the history of animal testing, the science underpinning it, and cases where animal models do not reflect humans (and why). 1933 lash lure mascara caused blindness, Lead to 1938 federal Food, drug and cosmetics act = mandatory testing 2013 modernization EU banned animal testing of cosmetics Not all research translates Case of things not being toxic to mice but being toxic to humans Fialuridine (FIAU) hepatitis medication Impacted mitochondria in humans the mouse transporter worked differently and left mice unaffected Alternative testing In silico computational models In Vitro Organiods vi. Relate recent developments in legislation and non-animal research around drug safety. 1933 lash lure mascara caused blindness, Lead to 1938 federal Food, drug and cosmetics act = mandatory testing 2013 modernization EU banned animal testing of cosmetics Trials designed to manage risk- Pre clinical exploring if and how a new drug may work Phase 1 (if approved) small numbers of patients, studying safety. Finding the max safe dose Phase 2 up to 300 patients further safety studying, ï¬​nding effectiveness and identifying side effects Phase 3 100- 1000s of patients safety and effectiveness, measuring effectiveness against existing treatment, monitoring side effects Alternative testing In silico computational models In Vitro Organiods viii. Describe the 3Rs and how they may be applied Replacement Avoiding or replacing the use of animals in areas where they would otherwise would have been used Reduction Minimising the number of animals used consistent with scientific aims Refinement Minimising the pain suffering, distress or lasting harm that research animals may experience *** BIOS101- learning outcomes week 2 session 3 i. Relate current knowledge on the origins of life, including theories surrounding self-replicating molecules and current uncertainties in knowledge. Origins of life Abiogenesis life emerging from chemistry Habitable world prebiotic synthesis polymers, vesicles biosphere Origin of life building blocks Urey and Miller 1953 experiment that produced amino acids sugars but lipids and fatty acids have no established synthesis pathway. Protocells Lipid membranes creates compartment Long chain fatty acids naturally assemble How it is formed is relatively unknown Used as an info storage mechanism Encoded catalysts Used for energy storage and transfer RNA World Hypothesis Early life based on RNA rather than DNA DNA is more stable, but limited in chemical reactivity Hydrogen bonds between strands remove the charge from the outside of the molecule RNA more reactive (less stable) Has a lot of spare capacity for reactivity as bases are not internally paired RNA Can both encode information and act as catalysts RNA can fold, and therefore form secondary structures Retains areas of charge and therefore has the capacity to bind. The enzymatic RNA are ribozymes When did life originate ? Two isotopes of carbon found, c13 and c12, enzymatic processes prefer c12 So organic carbon produced through life are c12 enriched and c13 depleted When carbon dating the carbon can be assessed ii. Describe the current evidence relating to the origins of photosynthetic metabolism, and current uncertainties. Photosynthesis Early planet high in co2 little o2 O2 generated from UV action on h20 but was quickly incorporated into metal oxides Earlier use of the lights energy likely to be used in non oxygenic photosynthesis splitting H2s- Using IR radiation lower energy for lower energy reaction Oxygenic Photosynthesis Cyanobacteria Used visible light at higher energy in presence of co2 to produce oxygen and a carbohydrate Geological evidence for oxygen Crystal deposition patterns Redox sensitive materials: Can only for and be stable wat low o2 At higher o2 they oxidise the soluble compounds lost to weathering Iron Pyrates Uraninite UO2 lost on geological strata formed after 2.3 billion years ago Why photosynthesis likely evolved before the rise of o2 Presence of unoxidized deposits, metal absorbs 02 reducing geology When the reducing factors are fully oxidised o2 can accumulate E.g. iron deposits Fe -> FeO -> Fe2O3 Banded iron formations indicate o2 absorption Time 2800 Mya 2500 Mya Stromatolites fossil cyanobacteria Cyanobacterial mats create rocklike formations stromatolites 3800 million years ago Photosynthesis evolved between 3.8 and 2.5 billion years ago The Great oxygenation event ( Preston Cloud ) Photosynthesis evolved Early 02 -> oxidation of metals Once metals have been oxidised the free o2 rises Oxygen dependent metabolism different means of releasing energy from carbon-carbon bonds (anaerobic) is inefficient Methanogens Fermentation Anaerobic cellular respiration Aerobic = more efficient Reverse of photosynthesis Equivalent to combustion Why does o2 risse if respiration uses it Carbon deposited in sedimentary rocks iii. Outline changes in planetary oxygen and some of their consequencesThe Great oxygenation event ( Preston Cloud ) Photosynthesis evolved Early 02 -> oxidation of metals Presence of unoxidized deposits, metal absorbs 02 reducing geology When the reducing factors are fully oxidised o2 can accumulate E.g. iron deposits Fe -> FeO -> Fe2O3 Banded iron formations indicate o2 absorption Time 2800 Mya 2500 Mya Once metals have been oxidised the free o2 rises Oxygen dependent metabolism different means of releasing energy from carbon-carbon bonds (anaerobic) is inefficient Methanogens Fermentation Anaerobic cellular respiration Aerobic = more efficient Reverse of photosynthesis Equivalent to combustion Why does o2 risse if respiration uses it Carbon deposited in sedimentary rocks iv. Relate changes associated with eukaryogenesis, including the origin of mitochondria and evidence for symbiosis, and potential drivers of this. Eukaryotic cells Nucleated (multiple linear chromosomes with histones) Organelles Complex internal membranes Synthesis sterols ( cholesterol which stabilise membranes) Ancestor of eukaryotes Carl Woese rRNA (ribosomal RNA) as encoded in the genome of all living things Its a structural component of ribosomes Phylogenetic marker Loops ( single stranded RNA ) fast evolving STems ( double stranded RNA) slow evolving Discovered 3 domains. eukarya derived from archaea and the bacteria. So eukaryotes ancestrally anaerobes Endosymbiosis Mitochondrion formed by symbiosis with a bacterium Mitochondria are relict bateria Bacterial aspects of mitochondria Double membrane Contain own circular DNA Possess own ribosomes- Protein synthesis inhibited by the same antibiotics as inhibits in protein synthesis in bacteria Divide like bacteria Mitochondria have 16S rRNA gene Derive from the alphaproteobacteria Evolution of mitochondria since eukaryogenesis Mitochondrial genomes are small Most ancestral mitochondrial genes transferred to the nuclear genome and proteins are targeted back to mitochondrion for it to work. Genes in eukaryotes originated from eubacteria and archaea Core genes ( translations ) tend to be archeal and others trend to be eubacterial And symbiotic fusions occur in the tree of life Therefore the tree of life is a poor metaphor v. Discuss current gaps in knowledge with respect to early eukaryotic evolution. Timing of eukaryotic evolution Molecular clock dating Fossil evidence Slide 39 1hr 15mins Were mitochondria acquired early or late? Eukaryote LCA carried mitochondria So could have been start of eukaryotic life Came late so displaced other eukaryotes Eukaryotic diversity 1. Origins of photosynthetic eukaryotes 2. A variety of other important microeukaryotes vi. Describe the use of 16S rRNA in reconstructing the tree of life, and deï¬​ne terms such as Last Universal Common Ancestor. 16S ribosomal RNA (rRNA) is used to reconstruct the tree of life because of the slow rate at which it evolves. Here’s how 16S rRNA is used to construct phylogenetic trees: Sequence comparison: Use software like BLAST or CLUSTAL X to compare sequences Tree-making: Use software like PHYLIP or MEGA 7.0 to create the tree Select an out-group: Choose a taxon that is outside of the group being studied16S rRNA is the RNA component of the 30S subunit of a prokaryotic ribosome.The 16S rRNA gene is about 1500 base pairs long and contains conserved regions and variable regions. The variable regions can be used to identify and differentiate between species. 16S rRNA is a crucial tool for identifying microbial organisms. It can be used to identify poorly described strains, mycobacteria, and novel pathogens.However, there are some limitations to 16S rRNA-based phylogenetic analysis, including: Inaccurate sequences in databases, Lack of a consensus definition for genus or species, Microheterogeneity in sequence within a species, PCR-amplification bias, and Cloning bias. (Google info make sure to look over notes alongside this ) vii. Outline processes involved with the evolution of photosynthesis in eukaryotes, and the origins of the diverse photosynthetic organisms we see today. 1 Photosynthetic eukaryotes have a single main origin Archaeplastida various algae ( rhodophytes and Glaucophytes ) And Viridiplantae green algae and plants All of these share a chloroplast with a single common origin Origin of chloroplasts A cyanobacteria inside a eukaryotic cell (endosymbiosis) Double membrane structure Own DNA Own ribosomes Proteins of cyanobacterial origin in nucleus cyano bacterial origin confirmed with 16S rRNA The emerging picture of life is not the bifurcating tree of life from Darwin, as there is coalescence of lineages through symbiosis Chloroplasts are more complex than mitochondria Archaeplastida algal cells have become symbionts of other eukaryotes Goes through a secondary symbiosis Symbiosis with cyanobacteria occurred more than once More recent evolution of a cyanobacterial symbiont in eukaryotic Amoeba ‘Paulinella’ Derived c. 100 Mya via symbiosis. Cyanobacterial genome still quite large Interesting, as amoebae in this group are natural predators of cyanobacteria => Predation and then maintenance as originviii) Describe the diverse lifestyles of microeukaryotes, including key taxa of importance to humans as parasites/pathogens. Many eukaryotes came to carry plastids The impact of this is Photosynthesis became spread across the eukaryotic tree Primary endosymbiosis -> (plants) Archaeplastids Primary endosymbiosis -> Paulinellia Secondary endosymbiosis -> other algal groups Lots of primary productivity in the oceans -> coccolithophores Coccolithophores Photosynthetic make caco3 shell dissolved from co2 40% of marine primary productivity Is a huge carbon sink Makes geology white cliffs of dover There are many Bacteriovorus/ algavore predators E.g. Ciliates Paramecium Can also be mixotrophs -maintain algae in cytosol instead of digesting them, farm for glucose Saprophytes (decomposers ) E.g slime moulds Micro Eukaryotic diversification produced simple but functional energy cycling Primary production alongside cyanobacteria Predators, decomposers alongside bacteria Animals and plants evolved to be parasitesWhen animals and plants arose some evolved to become parasitic Apicomplexa Gregarines (invertebrate guts); coccidians (vertebrate guts); haemosporida (vertebrate blood – e.g. Plasmodium) Toxoplasma (vertebrates) Microsporidia (obligate intracellular parasites common in invertebrates) Kinetoplastids: Trypanosomes ,Leishmania (sleeping sickness, Nagana, leishmaniasis) Giardia (gut parasite) Entamoeba (gut parasite) Oomycetes (e.g.Phytophthora potato blight) Important partners Corals require symbiodinium alga Enabling the construction of coral reefs which are a major ecosystem *** Nucleic acids and replication DNA and RNA are closely related molecules, but have distinct roles in the cell Structure of DNA strands On the right shows a nucleotide Multiplied up to make a polymer Ribose sugar consists of 5 carbons Named different based on RNA and DNA RNA is ribose which has an OH on 2’ DNA is deoxyribose with has no OH just H on 2’ Base attached to a sugar = nucleoside Base attached to sugar phosphate nucleotide Adenine base become adenosine with nucleoside in RNA And 2’ deoxyadenosine in DNA Then adenosine monophosphate when attached to singular phosphate groups Nucleic acid bases All planar molecules and aromatic Purines bicyclic e.g. adenine and guanine Pyrimidines monocyclic e.g. cytosine, Thymine and uracil Difference between Thymine and Uracil is in the C-H3 on thymine is a C-H on uracil Phosphodiester bonds Connects the 5’ of one to the 3’ of the other from sugar to sugar Due to the 5’ and 3’ connections there is directionality to the strand Every strand has a free 5’ end and the other end has a free 3’ and this defines the direction There are a series of ingenious experiments that led to the realisation that DNA was the genetic material DNA as genetic material Griffiths 1928. Frederick Griffiths, who had shown that a virulent strain of the bacterium Streptococcus pneumoniae, termed the S strain due to its smooth outer capsule, could ‘transform’ bacteria of a non-virulent R or rough strain so that they gained its virulent characteristics. Mice injected with either live R strain bacteria, or heat-killed bacteria from the S strain, did not develop disease. However, co-injection of the live R strain and heat-killed S strain caused the mice to die. This was the discovery of transformation Avery, Macleod and McCarty 1944. Evidence that DNA is the genetic material Rather than injecting bacteria into mice, the team used an assay that allowed them to detect whether transformation of the R strain occurred by observing the bacteria in culture They experimented with a variety of methods for purifying crude extracts of heat-killed S strain bacteria and established a protocol that gave them a relatively pure extract that was still able to transform the R strain when mixed with it. They subjected the purified material to chemical analysis and they also treated it with a panel of enzymes. At that time, they were unable to buy pure DNase enzymes ‘off the shelf’ so they used extracts of enzymes prepared from a number of different animal tissues. They tested the ability of these extracts to break down DNA by using them on pure DNA samples from other sources. DNA, a nucleic acid, has produced a change in S. pneumoniae bacterial cells that enables them to produce an entirely different substance, the smooth bacterial capsule. They also note that production of the capsule must involve the transformed cells carrying out a series of enzyme-catalysed reactions. At that stage the structure of DNA was unknown, and the researchers had no idea of the mechanism by which DNA could enable this to occur. Hershey and Chase 1952. Watson and Crick intuited the DNA double helix structure based on experiments done by others – Wilkins, Franklin, Chargaff Fibre Diffraction Maurice Wilkings, Rosalind Franklin and Raymond Gosling X-ray diffraction produced results proving DNA as: helical structure repeats at 0.34 and 3.4nm -2nm wide -phosphates on outside -Two strands Chargaff’s rules In any DNA the amount of guanine is equal to the amount of cytosine and the amount of adenine is equal to the amount of thymine, so the ratio of purine to pyrimidine bases in DNA is 1:1. Directionality is from 5’ to 3’ , DNA is antiparallel as the two strands go in opposite directions at any end of the two stands there is one 5’ and one 3’ DNA and RNA most likely have different evolutionary histories, with DNA evolving from RNA RNA world and ribozymes The proposition that RNA predated DNA and therefore proteins in evolution, Ribose was a more easily accessible molecule in early chemistry RNA could carry information and replicate itself Why DNA evolved from RNA RNA is an unstable molecule as the 2’ hydroxyl is close to the phosphorus and can attack it This results in the breaking of the backbone If conditions become especially alkaline the RNA becomes even more unstable and will continually attack itself DNA is very stable Uracil and thymine ? Cytosine does not make a very stable molecule as a base, as slowly over time it loses the end of the amino group and turns itself into uracil. The Thymine (with has an extra methyl group) is there to label the actual Uracil in the DNA sequence So the deaminated Cs that are now Us have no methyl group labelling them Uracil glycosylase is an enzyme is there to remove the uracils that are deaminated cytosines, but will not remove the methyl labelled ones RNA initially had a dual role replication and catalysis RNA having catalytic effects with properties like enzymes are called ribozymes RNA is involved in all stages of proteins synthesis RNA can synthesise RNA using an RNA synthesising ribozyme RNA can adopt complex 3-D structures Due to being single stranded, has a tendency to fold up into more complicated structures For example tRNA In these structures can have regions of base pairing and regions without, so the sequence is not a continuous double helix leading to complex 3D structures The 2’ OH of RNA is very important. In the B DNA structure, RNA does not structurally fit into it as of the 2’ hydroxyl , so a helix of RNA therefore has to be different. The Helix involving RNA is the A form of DNA DNA in cells is always B form, though if you completely dehydrate B form it cna turn into A form Ribosomes contain both proteins but a large amount of RNA molecules E.g. 16S ribosomal RNA in E.coli RIbosomal RNA in 3D The complementary nature of the DNA strands explains how replication must take place but there are complexities that also arise directly from the structure There is a convention that when drawing a single strand of DNA or RNA the 5’ is on the left and then you go right. The double strands will be labelled with which ends are which e.g. Due to the specificity of base-pairing the two sequences are complimentary If you know the sequence on one strand you can predict the other as they carry the same information Semiconservative The product helices contain one original strand and on new strand Size of DNA Diameter is the same as the distance of approximately 10 base pairs DNA molecules are enormously long, Viruses can have up to 200,000 base pairs in a single molecule In the largest human chromosome, the DNA would be 10cm long Bacteria In Bacteria DNA tends to be a circle: The synthesis of DNA seems to start at one point, but proceed in two directions, So you have two replication forks going around DNA replication DNA is always synthesised from the 5’ end to the 3’ end Energy is required in replication This energy comes from the fact that the molecules deoxy triphosphate, despite the fact they are deoxy, the break down of the triphosphate provides the energy required to make a new phosphodiester bond Synthesis requires primers RNA polymerase makes a primer called primase DNA polymerase extends the primer Antiparallel nature of DNA When forming the replication fork, as DNA is always synthesised in the same direction, it cannot work the same way on both strands. One strand is set up for synthesis and this is the leading strand, where the synthesis goes from 5’ to 3’ as the fork moves along But on the other strand you’d have to go back and synthesis the strand, as it is backwards To help deal with this during replication, the lagging strand is synthesised discontinuously in short segments going backwards These short segments are called Okazaki fragments Each one starts with a piece of RNA This leads to a complicated structure : This model does not represent the helix either !! DNA Proteins Macromolecule DNA and RNA encode and synthesise proteins - Proteins do almost everything else Protein functions and examples - Catalysis - enzymes - Structure - collagen - Transport - transport through membranes, Haemoglobin ( transporting oxygen) - Signalling - Insulin - Storage - ferritin - Movement - actin and myosin - Defence - antibodies - Control - 434 repressor - controls transcription of particular genes - Buffer - Protein Glossary - Amino acid - Peptide - Polypeptide - Prosthetic groups - Post translational modifications Diversity of proteins - 20 amino acids - 20 possible options at each position Amino acids Alpha amino acids - L-amino acids - exist in nature used to make proteins - stereoisomer D is not found in nature Charged amino acids - Negatives have a carboxyl group Non-polar - hydrophobic Polar + others Peptide bonds - Attaches amino acids - Formed through condensation so requires energy - This connection is chemically an amide - Planar - Almost always trans - same groups are on different sides across the bond - Can rotate fairly freely, peptide bond itself does not rotate but amino acids either side do to allow protein structures Peptide sequence - primary structure N- terminus and C-terminus The conventional direction and this sequence is the primary structure Secondary Structure - Function of the backbone rather than side chains - Can be either alpha helix or beta pleated sheets - - Alpha helix and beta pleated sheet - caused through hydrogen bonds - Beta sheets are antiparallel and parallel : Tertiary structure - Secondary structure elements folded together incorporating loops of the protein sequence - Function of the whole sequence - Packing of the side chains - Caused through hydrogen bonds and electrostatics - Most important is the packing of hydrophobic (non-polar) side chains inside to exclude water - Look at 39 mins in for entropy comment Hydrophobic effect - Water is rather ordered on the surface of hydrophobic molecules - Crowding of these molecule exclude water - The entropy of the water increases Disulphide bonds - Oxidation of two cysteine amino acids in close proximity - forms cystine - Occur in extracellular proteins - E.g. Insulin and antibodies Quaternary structure - - Non- covalent interactions - Protein-protein complexes - E.g. Haemoglobin Protein folding - - Anfinsen 1961 - ribonuclease A If you add urea and a reducing agent to unfold the add oxygen slow enough the activity of the protein will So the sequence is what determines the bonds - Chaperone proteins - proteins which aid other proteins - Many proteins contain related folds - the folds recur - Rossmann folds - similarities across different proteins. Same secondary structure sequence Structure Domains - - Proteins are not a singular monolithic fold - Pyruvate kinase - enzyme producing ATP as the final step of glycolysis is an example - 3 separate folded piece attached with looser folds - Each of the different sections of folds are called domains Structural determination Protein purification - Chemical methods that purify proteins based on charge size and other properties - Purification followed by SDS polyacrylamide gel X-ray crystallography - Treatments to cause protein to crystallise - This causes the protein to be crystallised in an ordered way - X-ray causes a pattern of reflections - Can calculate distances between different types of atoms - Can figure out electron density - Knowing the sequence and electron density can help form a structure - Difficult due to requiring crystals - not always possible - Only produces static image,No dynamics NMR - Signal for each type of atom - Figures out spatial connection - Works in solution - works for any protein but not too large - Can see dynamics - Can do experiments with drug binding to see interactions of protein Cryo-electron microscopy - Samples of protein are rapid frozen in ice - Can see them from a range of angles - Group into different classes and average images, superimposing them to map the proteins out - Can use larger complexes - No crystals required - Can study membrane proteins AI - Alpha fold - Artificial intelligence and deep learning methods - use existing 3-D data and sequences to formulate structure - Allows structures of all theoretical proteins, though accuracy is unknown and does not work Well with non-protein components Additional functionalities - Coenzymes and prosthetic groups - Non-protein components of proteins, especially enzymes, providing the chemistry and functionalities that the amino acids themselves can - May be covalently or noncovalently bound to the protein - E.g. Fe (Haem), Pyridoxal phosphate (4% of all enzyme activities require this) Post-translational modification - The covalent attachment of other chemical entities to proteins - Provide additional functionality or change their behaviour - E.g. phosphorylation (most used) , acetylation, methylationProteins do everything There is a huge diversity of possible proteins The 20 amino acids provide for very complex structure a Secondary structure makes up the core scaffold of many proteins Protein folding is driven by the ‘hydrophobic’ effect Many proteins share folds and domains There are multiple complementary methods to determine protein structure Protein function is supplemented by prosthetic groups and post-translational modifications *** Proteins, electrons and ATP Bioenergetics - - Involves many different tissues, cells, organelles, complexes and molecules - But it all boils down to proteins and electrons … and photons Metabolism - What is it for? Its fundamental for life - The reduction power of co2 to c-h - Of high energy electrons to molecules and energy Acquiring energy and materials - 3 formats of life: 1) inorganic - chemolithotrophic 2) organic - chemoorganotrophic 3) Light - phototrophic chemolithotrophic chemoorganotrophic Phototrophic Redox reactions - Redox reactions must occur together - Its a net oxidation-reduction reaction - A reduced + B oxidised = A oxidised + B reduced Relative energy values of some redox pairs important in biology ; Metabolism - anabolism - The synthesis of complex molecules from simpler ones, - using energy in the process E.g. NAD[P] + and. NAD[P] + H + H + These reactions are controlled by a specific dehydrogenase NADP must be bound to an enzyme during its redox reactions Metabolism - catabolism - The break down of complex molecules into simpler ones - Releasing energy in the process Using the electrons to provide energy - electron transport chains - Redox gradient The components of ET chains are arranged in an order of decreasing reduction gradient - the redox gradient A lot of this requires iron and copper. Components of electron transport chains used as electron carriers - Flavins - Quinones - Cytochromes (proteins that transport electrons and transfer energy within cells) - Metal-sulphur (FeS and CuS) centres Cytochrome [C-type] This is Haem The protein gradient - The G obtained from electron transport is used to pump protons across a membrane 5 oxidation states - Free energy from oxidation of carbon compounds Complex chemoorganotrophic organisms take e- from multiple redox reactions - NAD acts as an intermediate e- carrier - Electrons cannot exist freely NAD provides the electrons The components of the ET chain are arranged in the order of increasing E Mitochondrial ATP - adenosine triphosphate - ATP activates protein function - Phosphorylation of key amino acid - Hydrolysed on the protein Example- mechanical action How is ATP regenerated using the H + gradient? ATP Synthase ATP Cycling - - ATP -work-> ADP -oxidation of fuel molecules-> ATP - ATP is not an energy store Phototrophic Where is this happening? Sugars, Lipids and Cellular Barriers 1. Recognise the basic structures of the main carbohydrate (sugar) molecules 2. Understand their primary functions - structural, metabolic Sugars - monomers of carbohydrates - 5- carbon sugars - structural roles - DNA, RNA, ATP, NAD , e.g. ribose and deoxyribose - 6- carbon sugars - energy roles - and some structural roles, e.g. glucose, fructose and galactose - Fructose is a structural isomer of glucose and galactose is a stereoisomer of galactose 3. Understand how a-1,4, b-1,4, and 1,6 bonds build disaccharides and different glucose polymers Main disaccharides - Sucrose - alpha glucose and fructose Maltose - glucose and glucose Lactose - glucose and galactose Glycosidic linkages - Glycosidic bonds are formed through condensation reactions, they link two monosaccharides to form disaccharides and polysaccharides - 1,4 glycosidic linkages - form between carbon 1 and carbon 4 of two monosaccharides - Alpha 1,4 glycosidic linkages - the orientation of every other glucose is flipped, the OH group on the alpha carbon of the first glucose is below the ring plane - Beta 1,4 glycosidic linkages - glucose monomers are linked in the same orientation, the OH group on the alpha carbon of the glucose is above the ring plane - 1,6 glycosidic linkages - forms between the carbon 1 and carbon 6 of two monosaccharides - 1,4 - form liner chains - 1,6 - create branching points 4. Appreciate how structural modiï¬​cations of basic sugar molecules lead to a diversity of polysaccharides Anomers of glucose An anomer is a stereoisomer of a carbohydrate that differs from another stereoisomer only at the anomeric carbon. The anomeric carbon is the carbon atom in a cyclic sugar that bears the aldehyde or ketone functional group when the sugar is in its open chain form. It can form either an alpha or beta anomer. Alpha is when the hydroxyl group is below the ring plane and the Beta is when the hydroxyl group is above the ring plane. The anomeric carbon has a property called the anomeric effect which is a preference for an electronegative atom to favour an axial orientation over an equatorial one. The alpha glucose polymers - Starch - amylopectin and amylose (alpha 1-4 linkages) - Glycogen (alpha 1-6 linkages for branching and 1-4 linkages ) Beta glucose Polymer - Cellulose - Beta 1-4 linkages - Allows hydrogen bonding between cellulose polymers Chitin - Forms exoskeletons - N- acetylglucosamine as a polymer 5. Understand the roles of some polysaccharides as glycans in glycoproteins and components of proteoglycans Glycobiology - Glycoprotein - glycans (sugars) attach to protein Blood groups - Proteoglycans - mostly sugar less protein - - Provide shock absorbency and lubrication properties - Brush like structures - Form a large part of cartilage and extracellular matrices - The sugar sections of proteoglycans are long repeats of disaccharides known as glycosaminoglycans (GAGS) - Lysosomal disorders of GAG breakdown - e.g. hunters and hurlers 6. Recognise the main features of the structures of triacylglycerols and phospholipids Fats and oils and waxes - Lipids - Triglyceride, triacylglycerol 18 carbons 1 double bonds at the 9th carbon 18 carbons 3 double bonds at 9th, 12th and 15th carbons Make notes on 1hr in slide 26 -30 Phospholipids - - Two fatty acids attached to glycerol - The third carbon in glycerol has a head group attached - Most have a phosphate group and some king of alcohol, which is very often charged - They are very polar - The the fatty acid tails are nonpolar - The fatty acid tails can be saturated or unsaturated - Can form micelles, hydrophobic core as the fatty acids cluster together - They exclude water increasing the entropy of the water - Form membranes, a sheet-like array of phospholipids in a bilayer, again all the tails clustered in the centre. - There are many different types of phospholipids. The difference is the final alcohol group which is attached to the phosphate. There are also other classes of lipids which do not fall into phospholipids of triglycerides. These include: Steroids and Terpenes 7. Understand how phospholipids can form bilayers as cell membranes Eukaryotic cells - Specialisations to help the grow larger and more complex - Energy - mitochondria and chloroplasts - Complex internal and external membranes - Sophisticated transport systems and internal cytoskeleton Membrane structure - Phospholipid bilayer - Flexible and fluid - Fluid mosaic model - lipids and membrane proteins can move in the plane of the membrane - Fluidity can vary - can be affected by temperature and unsaturation 8. Understand the dynamic nature of the membrane structure, in terms of phospholipid diversity and the function of cholesterol Phospholipid components - †¢Phosphatidylserine (PtdSer) •Phosphatidylethanolamine (PtdEtn) •Phosphatidylcholine (PtdCho) †¢Phosphatidylinositol (PtdIns) •Sphingomyelin •Glycolipids Membrane composition - This varies between species and between membranes within cell. - Inner and outer face can vary e.g. animal cells, plasma membrane - Cytoplasmic face - Phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol - Extracellular face - Phosphatidylcholine, sphingomyelin (also contains choline), glycolipids - Enzymes that use active processes to flip certain phospholipids from one side on the membrane to the other Cholesterol - - Sits between in gaps caused by unsaturated chains - Has a high affinity with sphingomyelin as the shapes fit together suitably Lipid rafts - Self-organised regions of the membrane as a result of the well fitted relationship between cholesterol and sphingomyelin, non-permanent, but more long lived. Membrane proteins- Transmembrane domains - integral proteins: Peripheral proteins - Can be anchored to phospholipids - GPI anchor 9. Appreciate the dynamic interaction between the extracellular environment, the cell membrane and the cellular internal structures (the cytoskeleton) Cytoskeleton - keeping the cell together from the inner surface of the cell Microtubules Intermediate filaments Actin filaments Gene Expression Genes Produce proteins - The idea of genes predates the DNA structure - Beadle and Tatum (1941) - Mutations ( alterations giving rise to a change in phenotype ) in Neurospora crassa can be localised to a particular point on a chromosome -They correlate with defects in particular enzymes in biosynthetic pathways in biosynthetic pathways. - they could see in the yeast species when the cells were dividing, and furthermore they could correlate these defects to particular enzymes involved in making particular products -so they hypothesised that genes are regions of the chromosomes that are responsible in some way for producing particular proteins Central dogma - Crick - The sequence of the bases of DNA must be which encodes the information - His Dogma was that DNA is responsible for making RNA which itself is responsible for making protein Replication - making DNA from DNA Transcription - making RNA from DNA Reverse transcription - Making a DNA copy from RNA (using reverse transcriptase) RNA editing - Messenger RNA can be edited, so that the final message that is translated is not alway exactly the same as was supplied by the DNA in the first place RNA replication - via RNA-dependent RNA synthesis, tends to be a result of duplicating viral RNA Codons - - Codons are three nucleotide - Week 2 session1 - Darwin’s Dangerous idea - the one tree of life Pre - reading notes - The process of evolution produces a pattern of relationships between species. The lineages evolve and this appears as splits in the tree, here modifications are inherited. So they appear as branching patterns of evolutionary relationships - The study of these evolutionary relationships forming the trees is called phylogeny. Reading trees of life - The root of the tree represents the ancestral lineage, the tips of the branches represent the descendants of that ancestor. - As you move from root to tip, the time has moved forward - When the lineage splits ( this would be due to speciation ) it appears as branching on the phylogeny. - In each speciation event the ancestral lineage will form two or more daughter lineages. - Phylogenies have patterns of shared ancestry between lineages, but each lineage has a part of it history which is simply its own - Each lineage will have ancestors that are unique, and they will have common ancestors, these are the last ancestors before speciation occurs and the lineage branches off - A clade is a grouping that includes a common ancestor and all the descendants - alive or dead - of that ancestor. - Clades are nested within each other, so they can include thousands of species or just a few. - The tips of phylogeny represent descendant lineages, depending on how many branches these are include the descendants at the tips can be different populations of a species, a different species or a different clade ( composed of many species ) When reading phylogeny remember - Evolution produces a tree-like pattern of relationships among lineages not ladder like - Just because you read the phylogeny from left to right, that doesn’t mean there is a correlation with the level of advancement. - Of any speciation even the choice of which lineages goes each way doesn’t correlate to any level of advancement either, it is arbitrary. Darwin’s Phylogeny - The I think diagram - Species that are extinct do no have a cap on the tip The cenozoic - i) Relate why we think the K-Pg mass extinction was caused by an asteroid, and the concept of ‘compost earth’. - after186My of dominance, dinos disappear from fossil record 65.5 Mya - Huge crater - Change in sediment through strata, sediment core (1 cm = 100 years) huge world events look different - Sediment from the K-Pg has abnormally high volume of Iridium - Sediment is full of fungal spores, due to such a high amount of death, decomposers thrive - After we had the rise of mammals, they were only a minor taxon until 65.5 Mya ii) Describe the biogeographic processes that make Australasian and South America mammal faunas distinct from others Australia and South America were separate continents when mammals were evolving. - Some stayed apart, some meet and interchange - Madagascar and australia stayed apart - Isthmus of Panama closure 3 Mya, 41% of south american mammals have evolutionary origin in the north. iii) Outline why C4 metabolism evolved in plants, and its biological and ecological signiï¬​cance. Oligocene environment - Lower atmospheric co2 at 500ppm - Lower water availability - Lower co2 availability - Plants close stomata to avoid water stress - C4 metabolism evolution - more efï¬​cient at lower CO2 and high temp C4 metabolism - C4 metabolism involves two cell systems - Concentrates co2 at the site of RUBISCO- New anatomy of leaves ( Kranz anatomy) - each mesophyll cell has a =n adjacent bundle cell, they have more vascular tissue - Warm season grasses and tropical grasslands rely on C4 metabolism - Involves Maize, Sorghum and sugarcane - The change in plants therefore leads to a change in animals. iv) List key features that distinguish primates from other mammals, describe the main primate groups, how they are related and formed and the dominant drivers of primate radiation. 1) rolling of shoulder joint 2) separate thumb joint 3) Stereoscopic vision 4) Brachiation - swinging from trees 5) larger brains 6) claws flattened into nails 7) typically one offspring per pregnancy 8) upright held bodies Split into two groups - Strepsirhines and Haplorhines Primates evolved in africa and later spread to madagascar (lemur radiation) and south america ( new world monkeys ) Madagascar separated from africa 150 Mya - v) Describe the origins of H. sapiens both from within great apes and in terms of ancestry of H. sapiens as a species. Outline how fossil and aDNA evidence supports these ideas. Great apes - originated in africa - Orangutan restricted to SE asia now but fossils indicate much further range Molecular evident we are sister to chimpanzee and bonoboGreater apes - Pan, Gorilla, Homo, Pongo - Miocene apes lived in dense forest - Approx 100 species of ape at the time - Cooling and drying of climate - apes returned to africa - Earth movement produced the rift valley in africa around 8 Mya - Forest shrank and open habitats expanded - Miocene apes went into a big decline - human ancestors were some of the miocene ape that lived through these events Humans and Chimpanzees - Relationship of humans and apes was Darwin’s most controversial idea - Genome sequencing is clear though - First Hominins ( bipedal apes of the human lineage) appeared in africa at the end of the miocene Ardipithecus - chimp/human ancestor skeletons in ethiopia from 4.3 Mya - Chimp like Brains size - Human like sexual dimorphism - Foot / and structure - bipedal Pattern of peopling - Genetic origins in africa ( mitochondrial eve) Reconstructing the recent past with aDNA aDNA = ancient DNA DNA preservation - dry, cold - Human remains in dry places, mammoths in very cold places = whole genome of extinct species ( well preserved in these conditions ) - Does not work for older than 0.8 Mya - aDna is fragmented, damaged - Can use massive parallel sequencing to obtain deep reads against a modern polished scaffold Three clades of human - Denisovians - Neanderthals- Modern humans Neanderthal biology - Near complete genome - Mutation in melanocortin 1 receptor = pale skin red hair - Share mutations with h.sapiens in FOXP2 = associated with language - Share mutations with h.sapiens in TAS2R38 = associated with tasting bitterness aDNA provides: â—​ Direct evidence that Neanderthals & Denisovians Interbred =hybrid individual â—​ Direct evidence of inbreeding =Neanderthals with excess homozygosity â—​ Indirect evidence of Neanderthal-human interbreeding =Modern human genome = 0-4% Neanderthal vi) Outline the concept of the Tape of life, and evidence for and against it. vii) Relate the theory of punctuated equilibria, and evidence supporting it. Darwin: evolution as gradual accumulation of changes over long periods of time Mutation rate is more or lose constant Macroevolutionary change is not Punctuated equilibrium - periods of massive change, periods of relative stasis.viii) Cite cases of biological and external changes that have had major impacts on the evolution of biodiversity Characteristics that define mammals - Lactation - Middle ear with three bones - Jaw hinge - Fur - Placentation ( common ) - Endothermy ( common ) Nearly all clades of mammals appear by 45Mya i) Deï¬​ne and Distinguish between colonial and multicellular life, and relate whether the trait of multicellularity has evolved one or many times. Multicellularity in eukaryotes - - Multicellularity : many cells and > 1 cell type - Only one cell type is colonial cellularity - Multicellularity evolved on multiple occasions - ii) Outline the ecological and evolutionary drivers of colonial and multicellular life. ii) Outline the ecological and evolutionary drivers of colonial and multicellular life. What forces drive evolution of multicellularity 1) Evolution of colonial form - beneï¬​t of size 2) Evolution of division of labour - genetic similarity of balls of cells ( basis for cooperation) they collaborate to physiological and reproductive goals. Evolution of colonial form - Motive force : a beneï¬​t to cells in groups, this is widespread in bacteria and eukaryotes as chains and bioï¬​lms, these divide not separate - they are sticky. Division of labour - specialisation leads to increased efï¬​ciency, differentiation is beneï¬​cial in colonies as more progeny if cells specialise. iii) Describe, and relate the evidence for, the Cambrian explosion. Cambrian - the appearance of abundant fossils 540 Mya - Burgess Shale in Canada Precambrian ( proterozoic 2.5Bya - 540 Mya ), deï¬​ned by paucity absence of animals, only plant fossils Cambrian explosion ( Phanerozoic 540 Mya to today) deï¬​ned by strata with abundant fossils and visible lifeiv) Relate the main phyla of animals in terms of basic biological features. Understand deeper groupings of animal form, and for any phyla be able to deï¬​ne whether it is bilaterian or not, and for bilaterians, if it protostome or deuterostome, and for protostomes, whether ecdysozoa or lophotrochozoa. There are 33 phyla of animalia Non bilateria- Porifera - tissue absent and asymmetrical - Blob like aggregations of cells - Sediment ( benthic ) feeding - Six cell types but no tissues - Ciliary movement - Divide through ï¬​ssion and fragmentations Cnidaria - radial symmetry - Two cell layers ( this is called diploblast (blast = layers )) - No coelom, gu or head - 02 via diffusion - passive transport - Asexual reproduction - No differentiated germ line - Predatory via stinging - Sessile and planktonic stages Bilateria involves - Deuterostomia and protostomia - Bilaterally symmetrical - Triploblastic ( three cell layers - endoderm, mesoderm and ectoderm) - Has a gut - Developed a head - Has a front and back - Head - sensory and mechanical functions of feeding Within bilateria - the protostome and deuterostome split Protostomia - formed mouth ï¬​rst, begins with spiral cleavage to form stoma Deuterostomia split - formed anus ï¬​rst, begins with radial cleavage to form stoma Lophotrochozoa - Protostome development - spiral cleavage - Molluscs ( sedentary, mobiles, highly complex cognition, shelled) - Cephalopods- Platyhelminthes ( flatworms, free living (turbellaria) parasites, no body cavity, digestive cavity but not through gut ) - Annelids ( segmented worms, marine freshwater and terrestrial, collagen cuticle (parapodia)) Ecdysozoa - Ecdysis ( molting ) - chitinous exoskeleton (grow and moult), segmented paired appendages, can adopt a head, thorax, abdomen body. - Arthropod diversity - Chelicerata, myriapods, pancrustacea - Nematodes (unsegmented) bacterivores, plant and animal parasites, pests and disease causing, biocontrol agents - Nematomorphs - parasites - Tardigrades - water bears - segmented, plant algal and bacterial feeding, very resistant to desiccation, anoxia, vacuum. - Priapulids ( penis worm ) Hyper diverse in cambrian, marine - Onychophorans ( velvet worms ) segmented without exoskeleton, nocturnal ambush Deuterostomes - Echinoderms ( hedgehog skin ) - Invertebrates - all marine aquatic - Larvae bilateral symmetric - adults pentaradial - Mesodermal skeleton - No CNS - Water Based coelom circulation - Regenerative Hemichordates - Invertebrates - Extant taxa - acorn worms - Tripartite body - Some characteristics with chordates( hemichordata ) - Branchial gill slits - Stomochord - rod down the back - Dorsal nerve cord Chordates - chord down the back, with dorsal nerve cord - Gill slits ( pharyngeal) - Post anal tail- Vertebrates and derived from chordates -> dorsal nerve cord => vertebral column Cephalochordates - lancelets marine Tunicates - sea squirts, marine, ï¬​lter feeding, colonial adults Vertebrates - agnatha( jawless), gnathostomata (jawed) v) Critically discuss whether animal life emerged rapidly in the Cambrian or had pre Cambrian origin. Cambrian explosion had fossils of Protostomes, Ecdysozoa, lophotrochozoa, deuterostomes The majority of bilaterian taxa appeared in the fossil record during the cambrian Ediacaran - fossils found precambrian, Tina Negus and Trevor ford What events promoted the cambrian explosion - Global temp change - Global oxygen changes Global temp - Snowball earth ended before ediacaran (precambrian) - Extreme cold with high glaciation - Low photosynthetic accumulation - Reflecting light - Ended by volcanic activity - co2 input Global Oxygen - Higher o2 enables multicellular animal function - Physiologically - diffusion cannot sustain aerobic processes of large sizes at low 02 - Low 02 = limited size aerobic organisms - Higher oxygen = more trophic levels vi) Outline current hypotheses for the external and biological drivers underpinning animal diversiï¬​cation. Higher oxygen enables multicellular animal function - Diffusion cannot sustain aerobic processes at large size at low O2 - Low o2 limited size of aerobic organisms Vision evolution drove explosion by enabling predation ? Complex food webs enabled by oxygenation ?Biological underpinning Organism Form = Development, from single cell -> complex organism through Cell division, death, and differentiation - orchestrated by expression of genes that give positional information =Hox genes Hox genes - Hox genes code transcription factors - Define position - Alter expression of other genes - Lead to development of complex forms Individual hox genes are found widely in eukaryotes - animals have a large array of them Number of copies and organisational complexity are linked Enabling bilaterian complexity Session 1 learning outcomes: i) Outline the antecedents to evolutionary theory, in terms of geology and palaeontology - Carl linnaeus, wrote Systema Naturae (1735), ordered biodiversity into Genus species such as Homo sapiens (1758) - James Ussher (1581-1656) used the bible to go backwards and ï¬​nd the date for the earth, 22nd October 4004 BC ii) Understand the basic divisions of geological time Geological time - James Hutton - Geologic strata - using rocks formation and sedimentary deposits over time - So the surface is the most recent and the further down the older the geology Geological time - - Divided into Eons, Eras, Periods and epochs - Eons are the longest and Epochs are the shortest. The Cambrian - named after cambrian rocks in wales - Surveyed coal mines They observed the strata above coal deposits And correlated fossils with strata Faunal succession - repeated changes in fossils present through strata Index fossils - indicates a particular geological period ( biostratigraphy ) Gideon Mantell - found the first dino, the Iguanodon tooth at Tigate Quarry, therefore found the idea of the mesozoic era Zoic - life Ceno - recent Meso - middle Paleo - old Phanerozoic - visible life Cenozoic - mammal dominated Mesozoic - dino dominated Paleozoic - pre-dino vertebrates iii) Describe how Darwin/Wallace theory gave rise to evolutionary theory linking micro and macro evolution. Darwin’s evolutionary theory - Evolution can be defined as a change over time - Fossil records are consistent with change over time- Without a mechanism to drive the change, this inference is weak Both Darwin and Wallace believed : Variation in living forms - within a species, in both nature and domestication - similarities and differences between species Descent by modification - Too many individuals to survive - Differential survival between individuals - Gradual change in traits in population - Leads to new species Artificial selection - can take a species to different phenotypes when select individuals are used over another for breeding If this selection occurred naturally would lead to spatial diversification and different species Darwin and wallace on natural populations - All organisms overproduce offspring - Population abundance has limiting factors such as predation, food, climate - Causes competition Theory of Natural selection - - Some individuals possess traits that cause slight advantages in competition - If the trait is inherited the next generation contains more individuals with the trait - Over time the species comes to resemble the variants with higher reproductive success as the trait is beneficial to compete If individuals vary in character, and some of that variation is heritable, and variants differ in mean number of offspring produced, then the next generation of that population will be biassed to variants that lead to a greater mean number of offspring so over many generations they become fit to the environment and adapt. Gradualism - E.g Hutton and Lyell - geological processes seen today are the same as in the past Very small yearly changes over a large amount of time equal a dramatic change in geological features. Darwin applied gradualism to natural selection - Small differences in fitness between individuals (microevolutions) lead to large morphological changes (e.g. new species) over time (macroevolution) Microevolution - macroevolution link : evidenced in species as the product of divergent selection and isolation Inspired by endemicity of islands ( organisms that are restricted to a locality or region ) 50% of species on the galapagos were endemic - variation occurred between islands within the galapagos.iv) For any particular evolutionary change, determine if it is a case of macro or micro evolution. Evolution is change over time - Microevolution - changes that occur within a species over times - Leads to diversification over space, distinct lineages - Eventually leads to macroevolution the pattern of biodiversity over deeper time - All leads back to a single origin v) Outline the three types of evidence for the one tree of life. For any piece of evidence, determine what type of evidence it is. Evidence for a single common origin - Conservation of molecules Conservation of structures Conservation of processes Conservation of structures - Cells - Membranes (lipid bilayers) - Membrane spanning proteins - Ribosomes Conservation of processes - Core genetic code - Transfer of information - Metabolisms and the enzymes involved - The use of protein modifications (phosphates, ubiquitin ) vi) Understand the concept of a phylogenetic tree, as the outcome of descent with modiï¬​cation. - The process of evolution produces a pattern of relationships between species. The lineages evolve and this appears as splits in the tree, here modifications are inherited. So they appear as branching patterns of evolutionary relationships - The study of these evolutionary relationships forming the trees is called phylogeny. - vii) Relate how DNA sequence can be used to establish a phylogenetic tree; from particular sequence assess which tree it supports ( training in additional work ) Using DNA - Phylogenetic trees Looking at the differences that are shared and not shared between species Helps to overcome the convergence Provides 1000s of characteristicsCannot use this on extinct species - Dead things don’t have DNA - So morphology is still used on fossils - Issues with time - need to find how old species are viii) Deï¬​ne analogous and homologous characters, and be able to deï¬​ne which category a particular character ï¬​ts into. Analogous - Different ancestry ( evolved separately ) perform a similar function, arise to due convergent evolution due to similar selection pressure in different taxa Homologous - Shared ancestry ( evolved from one common ancestor ) may not have the same function in descendants ix) Determine how current traits can be mapped onto phylogenetic trees, and the number of evolutionary transitions estimated ( training in additional work ) We estimate the tree of life via evolution due to descent of modification, closely related species share more features than distantly related ones, both anatomy + physiology based and DNA based Related species have shared homologies For extant taxa - DNa defines phylogenetic trees DNA provides many 1000s of characters therefore helps to overcome convergence x) Outline how different methods can be used for dating evolutionary events, and outline the best method for dating for a particular given evolutionary event. Carbon Dating Recent biological material Carbon 14 decay - > carbon 12 T50(half life) = 5740 years Ancient rock materia Potassium 40 -> argon 40 t 50 = 1.248x10 9 years Slide 59 14.19DNA sequence divergence may be able to estimate time from common ancestor (the molecular clock) Nucleotide and amino acid substitutions accumulate over times Presumed to occur at a constant rate Able to calibrated based on know events (fossils) Egg came before chicken Animals evolved back into the sea three separate times xi) To discuss varying religious views on biodiversity within the Judeo-Christian tradition and how these do (or do not) reconcile with current evolutionary thinking. Young earth vs old earth Young earth - Species created separately designed by a creator 6000 years ago - Variety of view regarding natural selection - Does Not allow for speciation - Only microevolution in terms of natural selection Old Earth - Earth is geologically ancient - Variety of views on evolution - Gap creationism - earth is old but biodiversity is not - Progressive creationism - mutation and selection exist + occasional interventions - Theistic evolution - god invented the rules, and let everything run Bio101- Philosophy of science What is and isn’t science? Demarcation - What are the key things that make science a science or non a science (pseudoscience) This is the demarcation problem, it is subjective so doesn’t allow for any theoretical grounding Rationalism - where knowledge can be derived from well reasoned arguments, is independent of senses, Rationalism is not directly proportional to intelligence it is an assumption Neuropsychological humility - understanding human cognition is imperfect, the human brain can be tricked, it can make mistakes. This is a foundational concept of scientific scepticism - an approach to knowledge that prefers beliefs and conclusions that are reliable and valid. Critical thinking - - Evaluate arguments made by others - Construct arguments of our own - Distinct from knowledge Important due to : - Having true belief is better than having false belief - False beliefs can be costly - True beliefs help understand the world Everyone is vulnerable to failures in critical thinking Need to be applying critical thinking to our own beliefs Arguments - An attempt to provide reason for a belief - Arguments are made up of statements - Statements are sentences that makes a claim that is either true or false - Arguments must have two or more statements Structure of an argument: 1) Look for an attempt to convince 2) Find the conclusion ( look for then end of the paragraph maybe ) 3) Find the premises Empiricism- ( as opposed to rationalism ) Knowledge comes from experience and evidence, experimental evidence is needed to determine the truth, evidence is independent from senses. The quality of the evidence is a direct result of the quality of the experiment Observational sciences - Observational science is not amenable to experiments Still uses evidence,A theory is scientific if and only if it can be falsified either by experimentation, observation or other appropriate methodology - Karl Popper’s view using falsifiability E.g. Aliens do not exist - this is falsifiable, can be tested and considered scientifically Rationalist - we only one example of biological life - Other potential examples are inaccessible - Is it rational to assume such a large universe has only one instance of life - Can use the Drake equation Empiricism - no confirmed radio signal indicative of civilisations at our level or above - Strong evidence of planets around other stars ( including habitable zone planets) - No evidence of life elsewhere in the solar system using robotic explorers Falsifiability - No current evidence, though the hypothesis can be falsified by gathering new evidence Alternative history of science - Why are we here? Emergent property - life arising out of chemical and physical complexity Biologist mechanisms Natural selection -> evolution - Not spontaneous - Gradual process, enhances an organism’s ability for survival and reproduction - Organisms resemble parents but have random variation - Not all offspring survive and reproduce, there is competition - Those which reproduce tend to be best adapted to the environment Thermodynamic laws 1. Energy can only be converted from one form to another 2. Entropy always increase (disorder increases) Entropy - Entropy is a measure of disorder - Larger more complexity molecules have lower entropy (more ordered) - Smaller more dispersed molecules have higher entropy (less ordered / more disordered) Gibbs free energy (G) - Available energy ( taking into account entropy ) - - Free energy = total energy - (temperature x entropy) Free energy (G) spontaneous processes in a system have to have a negative change in G, this can be caused by a negative change in H so energy is released to the surroundings or there is a positive change in entropy ( so entropy increases ) Spontaneous processes - Gravitational motion - Diffusion - Chemical reactions More free energy = less stable = greater work capacity In spontaneous processes free energy decreases = more stable = released free energy used to do work Less free energy = more stable = less work capacity Energy coupling - organisms are low entropy - To increase free energy - Use free energy from another process Couple two processes together Such as hydrolysis of ATP or photosynthesis Assembling DNA Session 5 - from the Cambrian to the Cretaceous Paleozoic Marine radiation of fishes - Origin of chordates in the Cambrian, - Fossils of Jawless fish (Agnatha) - E.g. Hagfish Silurian Diversification of fish - - 450-420 Mya Jawed Fish radiation (Gnathostomata) - Chondrichthyes ( cartilaginous fish ) - sharks and rays - Osteichthyes - bony fish, ray finned ( actinopterygii- teleosts ) and lobe finned (sarcopterygii - Coelacanth ) Enabling feature - Genome Duplication - Early chordates had two genome duplication events - Four Hox gene clusters resulted from this - Therefore enabling morphological complexity such as the jaws and limbs The greening of the land - Silurian Devonian Terrestrial Revolution Land plant life cycle evolved from algal ancestors Bryophytes - early land plants ( Liverworts and Moss ) - Long haploid phase - Short diploid phase - No Vascular - Do not require soil - Evidence through fossilised sporangia - Moss has also evolved stomata - gas / water regulation Land plants were accompanied by terrestrial fungi - Evolution of desiccation-resistant fungal hypha came from aquatic form - Hypothesis that fungi enabled plant life through symbiosis - = water and iron gathering - Fungi may have preceded plants into terrestrial environments Plant death = organic bearing soils - Soil = plant matter breakdown - Bryophytes may not need soil but they do create it - So soil enables larger plants Vascular plants - First vascular plant - Cooksonia - Phloem XYlem transport systems- Bifurcating growth ( they branch ) - Increased in size due to process of lignification ( using lignin for rigidness ) - Leaves and fronds - above ground photosynthetic surfaces - Evolved at multiple points Extension of the diploid ( sporophyte ) in Vascular plants = longer lived organisms Vascular plants = richer soil - Deeper roots ( leads to the degradation of rock and mineral release) - Run off of the Po4 and NO3 that benefits plant growth may have poisoned oceans via eutrophication - Lead to devonian mass extinction All major plant forms had evolved by the carboniferous - other than flowering plants Land plant evolution was accompanied by terrestrial arthropods First insects - flightless Derived from Crustacea (in Silurian) Devonian -> winged forms + millipedes, and Arachnea The Carboniferous CARBONIFEROUS ROCKS - appearance of organic carbon rich deposits, from coal beds/ measures. Change in plat life - coal beds have many plant fossils - Large wooded plants appear by large ferns - Derived from lowland marsh / wetland Why the increased deposition of organic carbon - Tall wooded plants become dominant - Wood is rigid because of lignin - They become tall - Lignin = complex carb - Decomposes slower - Slower decomposition = more organic carbon buried and coal strata Consequently - increase in 02 O2 increased- biological consequences - Insect gigantism - giant millipedes and cockroaches O2 limits body size where diffusion supports gas exchange - O2 content of water increases with latitude and reduction in salinity O2 enables fire, 10-20% if coal beds are charcoal based - Carboniferous = lots of wildfires - Charcoal deposition mean carbon sink remains despite co2 creation - Ecosystem is stabilised by wet conditionsRadiation of tetrapods - Warm wet climate and green terrestrial biome allowed movement out of the water - Amphibian lifestyle - linked to laying eggs in water - Closest ancestors of amphibians - the lobe finned fish Gigantism in Amphibian - Sole tetrapod group - dominant predators of the carboniferous Proceeding the Carboniferous - the Permian - Period of drying alongside a hot climate - One large landmass ( pangea) - Drying made poor environment for amphibians - selection for water retention - Leading to reptiles - Saw rise of metamorphosing insects ( drivers of metamorphosis is unsure ) - Mass extinction - end of the permian has largest mass extinction in fossil records known ad the great dying Reptiles adaptations away from water - - Amniotic egg ( zygote in fluid filled cavity called an amnion) - Chorion and shell of egg allows gas exchange but retains water - Keratinous scales - water impermeable skin - Alteration in excretion- uric acid instead of urea so retains water - Internal fertilisation - land necessitates transition to internal fertilisation Mass extinction - High volcanic activity - Massive so2 and co2 release - Ocean acidification - Reduction of primary productivity - Death of the consumers Mass extinction doesn’t hit evenly - Mesozoic - age of DINOS Growth rates accelerate in endothermic species Diet is clear from teeth Brain size scales with body size as for other reptiles - more like reptile than bird Likely did not have the complex cognitive capacity of birds and mammals Mammals - Crossed over with dinos - Derived from synapsids (non-dino reptiles, no living examples) - Remained a minor taxa during dino times Hadrocodium - An extinct mammals form- Lived during early jurassic - Insectivores, nocturnal - malleus -incus-stapes derived from jawbone - Very good hearing Birds -160 Mya - Evolved from theropod dinosaurs - Small lightweight feathered and winged - Evolved gradually over tens of millions of years Many non-avian dinosaurs had feathers ! Bird feathers and mammal hair are both modified reptile scales (these are fishes dermal teeth) Flowering Plants - Angiosperm - First fossils - 130 Mya - Fast growing compared to gymnosperms (conifers) - Initially wind pollinated insect pollination (110 Mya) Plant and insect diversification - Massive plant diversification - 70-100 Mya - Loss of gymnosperms in tropics - Beetles diversified followed Ehrlich and Raven - coevolutionary game changing Plants and their herbivores - escape and radiate process - Plant group - novel defences - Escapes herbivores and colonise new niches - Radiates - Herbivores that establish into that group - Larger number of new niches - And more radiation History of life - Macroevolution Carl Linnaeus - System of nature - Invented the idea of Genus Species ( Latin nomenclature ) Geological time - James Hutton - Geologic strata - using rocks formation and sedimentary deposits over time - So the surface is the most recent and the further down the older the geology Geological time - - Divided into Eons, Eras, Periods and epochs - Eons are the longest and Epochs are the shortest. The Cambrian - named after cambrian rocks in wales - Surveyed coal mines They observed the strata above coal deposits And correlated fossils with strata Faunal succession - repeated changes in fossils present through strata Index fossils - indicates a particular geological period ( biostratigraphy ) Gideon Mantell - found the first dino, the Iguanodon tooth at Tigate Quarry, therefore found the idea of the mesozoic era Zoic - life Ceno - recent Meso - middle Paleo - old Phanerozoic - visible life Cenozoic - mammal dominated Mesozoic - dino dominated Paleozoic - pre-dino vertebrates Darwin’s evolutionary theory - Evolution can be defined as a change over time Fossil records are consistent with change in time Without a mechanism to drive the change, this inference is weak - Variation in living forms - within a species - similarities and differences between species Descent by modification - Too many individuals to survive - Differential survival between individuals - Gradual change in traits in population Leads to new speciesArtificial selection - can take a species to different phenotypes when select individuals are used over another for breeding If this selection occurred naturally would lead to spatial diversification and different species Darwin and wallace on natural populations - All organisms overproduce offspring - Population abundance has limiting factors such as predation, food, climate - Causes competition Slide 36 The tree of life Evolution is change over time - Microevolution - changes that occur within a species over times - Leads to diversification over space, distinct lineages - Eventually leads to macroevolution the pattern of biodiversity over deeper time - All leads back to a single origin Evidence for a single common origin - Conservation of molecules Conservation of structures Conservation of processes Conservation of structures - Cells - Membranes (lipid bilayers) - Membrane spanning proteins - Ribosomes Conservation of processes - Core genetic code - Transfer of information - Metabolisms and the enzymes involved - The use of protein modifications (phosphates, ubiquitin ) Anthropocentric - humans at the top of the system Evolutionary - no species is over anotherEvolution - how do we estimate the tree of life - Descent with modification - Closer related species share more similar features than distant related ones (found using anatomy and physiology bases features) - Homology - related species have shared, derived traits Issues - convergent evolution - Similar selection and pressure in different taxa - Leads to a similar / same characteristic or function that was actually derived independently - These are analogous rather than homologous structures Using DNA - Phylogenetic trees Looking at the differences that are shared and not shared between species Helps to overcome the convergence Provides 1000s of characteristics Cannot use this on extinct species - Dead things don’t have DNA - So morphology is still used on fossils - Issues with time - need to find how old species are Carbon Dating Recent biological material Carbon 14 decay - > carbon 12 T50(half life) = 5740 years Ancient rock materia Potassium 40 -> argon 40 t 50 = 1.248x10 9 years Slide 59 14.19 DNA sequence divergence may be able to estimate time from common ancestor (the molecular clock) Nucleotide and amino acid substitutions accumulate over times Presumed to occur at a constant rate Able to calibrated based on know events (fossils) Egg came before chicken Animals evolved back into the sea three separate times

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