Domain

Explanation

Since ancient times

• As embodied by our roots as curious living things,
• People often go exploring for new things
• Whether it be from necessity for survival
• Or from curious nature
• There are plenty of living things besides humans,
• Both flora (vegetation) & fauna (animals)
• In the furthest ancient times, humans are really nothing more than more socialised & organised primates
• Era of survival: human groups gather for protection & cooperation in order to survive in the harsh wilderness; foods need to be hunted; weather elements are awesome & supernatural
• Era of subsistence: separate human groups have stabilised into sustainable units capable self-protection & self-maintenance in terms of food, water & shelter; people become more socialised & interconnected; they begin to observe, experiment & perform less from survival necessity & more from practical needs; observe that food plants growth cycle; experiment with common plants & invents the earliest agriculture; captured animals need not all be killed, some can be conserved; observe that animals mate & reproduce with like kinds just like humans do; experiment with common animals & invents domesticated animals; herein begins practical genetics (selective breeding); weeding out undesirable strains or traits & planting or breeding for the best
• Era of dominance: the most successful human groups begin to spread their influence across other human groups; herein begins civilisation from colonisation; concepts (know-why) & technologies (know-how) that are otherwise separated & unavailable for other groups are now assimilated into the dominant groups or are rejected/diminished/extinct; from assimilation comes further capacity beyond subsistence & dominance; culture, history, the arts & science flourish as the outer layers of dominant groups engage in colonisation & the inner layers engage in preservation, promotion & preparation
• From experiences:

1. Stable varieties always breed the same kind, while unstable ones have variable offsprings
2. Two close species can be mated to produce hybrids
3. Occasionally, all varieties would produce slight variations of themselves, "sports"
4. Mainly trial-and-error

Spontaneous generation

• The mistaken myth that life arose & was controlled by mysterious & supernatural forces
• An example is that maggots "arise" from dead, decaying matter
• This myth was shaken by Francesco Redi in 1668 with the use of meat in open & closed jars: maggots only appear in open jars
• This myth is ended by Louis Pasteur in 1864: "Never will the doctrine of spontaneous generation recover from the mortal blow that this simple experiment has dealt it"

Plants

• Anton Van Leeuwenhoek makes systematic use of the microscope to study fleas & saw bacteria & discovered sepa, cells
• William Harvey convinced that all animals must come from eggs
• Sexual nature of plants largely resolved by Camerarius: male (protruding anthers parts for pollen) and female (stigma) parts of flowers
• Pollination is equivalent to fertilisation where pollen (sperm) meets eggs to produce fruits of labour (babies)

Mendel

• Gregor Mendel (1822-184): discovers the first laws of inheritance through systematic breeding of pea plants in his spare time
• Principal results:

1. Law of inheritance: hereditary traits are governed by "factors" (genes that retain their identity in hybrids
2. Law of dominance: an "allele" of a gene may be dominant over another (recessive), such that the dominant allele has a higher chance of being passed on, but the recessive would re-appear in later generations (can be simplified by mathematical explanations)
3. Each offspring has two copies of each gene - one from each parent (assuming bi-parent relationship)
4. Law of independent assortment: all combinations of alleles are equally likely with different alleles sorted out randomly & independently [verified wrong due many genes lie on the same chromosome, hence they not totally independent when they share a chromosome in common]

• Verified by Hugo Devries, erich von Tschermak & carl Correns

Cells

• All living things are made of cells - smallest unit of living matter
• Robert Hooke first noticed cellular structure of cork
• Cells come in all & any forms; come from division of precedent cells
• A typical cell (whether plant cell or animal cell: plant cell is typically 3 times that of animal cell):

1. Nucleus: core of the cell, contains all genetic information (nucleotides, DNA, chromosomes, proteins), where cell division originates
2. Cytoplasm: surrounds & protects the nucleus; carries out instructions (through RNA messengers) from nucleus to ribosome (for protein making) & mitochondrion
3. Cellular membrane: to protect cell interior and maintain integrity of the cell

• There are both single-cell organisms & multi-cellular organisms

Mitosis

• Mitosis is the division of a single precedent cell into two or more cells
• 3 types of mitosis:

1. Binary fission: single cell reproduces & divides into two equivalent cells
2. Fragmentation
3. Splintering

• Mitosis process using binary fission:
• Inside nucleus: chromosomes duplicate them using free-flowing nutrients of the nucleus & they remain attached to a spot called the centro-mere
• Chromosomes thicken & become visible under microscope
• Nucleus membrane dissolves & chromosomes line up on a fibrous spindle formed
• The spindle fibres tug the chromosome pairs apart by dividing the centro-meres
• The chromosomes arrive at the different poles (new nuclei) & the spindle disappears
• The nucleus membranes re-form, chromosomes unwinds & the cell divides into two

Meiosis

• Chromosomes of all species are even, as sperm and egg (zygote) [gametes] are single cells with only half the normal number of chromosomes
• Reproduction cells: germ cellsThe two copies (even) of chromosomes form homologous pair
• Humans have 23 homologous pairs of chromosomes: in only one pair, female has two X (longer) chromosomes, while male has one X and one Y (shorter) chromosomes
• Meiosis is the cell division specially for making gametes (i.e. reproduction cells):

1. In nucleus, chromosomes double & thicken
2. Homologous chromosome pairs form - different
3. Spindle fibres form & separate the pairs
4. When the separated chromosomes reach the poles, mitosis occurs

Realisation

• Mendel's laws verified by Hugo Devries, erich von Tschermak & Carl Correns
• Genes lie on chromosomes and many genes lie on one chromosome
• The two copies of a given gene lie at the same point on homologous chromosomes
• Cell with a single set of chromosomes: Haploid (male honey bees, fungi, asexual creatures)
• Cell with two sets of chromosomes: Diploid (mammals, birds, plants)
• Cell with multiple sets of chromosomes: Polyploid (plants)

Gene mapping

• Genes are actual, physical & biochemical objects
• Genes lay some order along the chromosomes
• Two alleles of each gene form a homologous pair
• Gene map: where each gene lies on each chromosome
• Gene mapping:

1. Make vast number of crosses between individuals with various pairs of traits
2. See how often each pair is separated by crossing over: looking at the offspring or phenotype
3. Plot them out: those most closely linked will be closest together

Crossover

• Law of independent assortment overruled due to:

1. Linkage between adjacent genes
2. Gene swapping called cross-over

• At short distance along chromosome: genes are closely linked & related or cross-over
• At large distance along chromosome: genes are relatively independent

Mutation

• Genes are mutable: they might no be copied exactly during mitosis or meiosis or crossover
• Genes do mutate from time to time, depending on circumstances & chances
• Mutation comes in the forms: varying genes or traits different from precedent copies
• Impacts of mutation:

1. Advantageous mutants: favours the mutant in the environment
2. Disadvantaged mutants: impedes progress of mutant population
3. Recessive mutants: phenotype of mutants with recessive alleles have lesser chance of forming

• Mutation agents:

1. Mutagens: chemicals
2. Radiation
3. Cancer: mutation in body cells (somatic cells)
4. Carcinogenic: cancer-causing & mutation-accelerating

Sex

• Process of reproduction
• By independent assortment, with alleles X & Y, with random & equal chance, the ratio of female:male is roughly 1:1
• Due to mutation & genetic defects, there are some variants
• Bees: male from unfertilised haploid eggs & females from fertilised diploid eggs
• Neo-sexual: no sex like larva of the marine worm Bonellia
• Asexual: a cell has two sexes with asexual reproduction

Other genes on the chromosome

• Baldness
• Colour-blindness
• Hemophiliacs: non-stop bleeding

E.Coli

• Multi-cellular organisms are very difficult to study due to the complicated molecular genetics
• Hence,
• A simpler organism is studied: the bacterium, Escherechia Coli
• E.Coli in short
• It strives in the intestines of humans & other animals
• The picture inside a cell:

1. Single chromosome: some tangled mass with long strands, double balls sliding along them (the site of some activity)
2. Some large, lumpy molecules are pulling apart & putting together various long stringy things
3. All around are bits of raw materials
4. Plenty of water

Macromolecules

• 6 basic elements/atoms:

1. Carbon
2. Hydrogen
3. Nitrogen
4. Phosphorous
5. Sulfur

• Basic molecules:

1. Water: H₂O
2. Phosphate: PO₄
3. Sugars: like glucose C₆H₁₂O₆

• Macromolecules:

1. Large, long chains made by stringing together many copies of identical sub-units, much like polymers
2. Polysaccharides: chains of sugars, like starch & cellulose
3. Lipids: having at least one end repelling water; form major component of cell membranes, animal fats & vegetable oils
4. Nucleotide: 3 components of a sugar, a phosphate & a base; where the sugar is either ribose or deoxyribose
5. Base: A, C, G, T, U
6. Nucleic acidsGoogle Search: genetics base: made up of many (millions) nucleotides - building blocks; those with ribose sugars are Ribonucleic acid (RNA); those with deoxyribose sugars are Deoxyribonucleic acid (DNA); both with differing bases from one nucleotide to the next - genetic molecular language
7. Proteins: most complicated macromolecules made of chains of amino acids (named after Uganda's dictator Idi Amin)

Proteins

• Most complex of all macromolecules
• Made up of different types of amino acids
• Amino acids: a standard chain connected to an arbitrary group to give different amino acids like glycine, leucine, cysteine, phenylalanine, tryptophan, asparagine, etc.
• Peptide: two amino acids chain
• Protein chain: polypeptide, multiple amino acids chain
• One example protein: hemoglobin (studied for 25 years by Nobel laureate Max Perutz)
• Every protein has a precise number & sequence of amino acids
• Mutual attractions among the amino acids cause the chain to coil up into compact & flexible shape
• Most proteins are … enzymes

Amino acids

• Amino acids: a standard chain (H, C, N, O) connected to an arbitrary group to give different amino acids like glycine, leucine, cysteine, phenylalanine, tryptophan, asparagine, etc.

Enzymes

• All enzymes are proteins which take apart or put together other molecules
• Each enzyme is responsible for just one specific reaction
• Enzymes remain unchanged during the process
• E.g. digestive enzymes break down large moelcules
• An organism is made of its enzymes
• In the 1940's, George Beadle & Edward Tatum worked with mutant strains of the common bread mold neurospora
• They discover:

1. The mutants lack certain nutrients because they lack some enzymes necessary to manufacture them
2. The mutation of a single gene led to the lack of a single enzyme
3. The metabolic role of the genes is to make enzymes
4. Each gene is responsible for one specific enzyme

• One gene, one enzyme
• Implies genes make enzymes
• All enzymes & proteins come in certain sequence, which determines its structure
• But,
• What are genes?

DNA

• Deoxyribonucleic acid
• 1920's: Fred Griffith experimented with two strains of the pneumonia bacterium, pneumococcus
• It was understood like this: the genes of the boiled fatal strain had survived & infiltrated the live mutant strain, transforming the latter into the fatal wild pneumonia
• 1940's: Oswald Avery identified this transforming factor as DNA (though until then, DNA is known but without much attention)
• DNA contains:

1. Sugar: deoxyribose
2. Phosphate
3. 4 bases:

• A: Adenine
• C: Cytosine
• G: Guanine
• T: Thymine
• Erwin Chargaff: composition of DNA varies widely between species, but the number of A = number of T; number of C = number of G
• Rosalind Franklin: from X-ray pictures, DNA probably has a helix shape with 2~3 chains
• 1952: James Watson & Francis Crick discover the DNA model:

1. By playing with scale-model atoms, they observe A fits with T & C with G through weak hydrogen bonding
2. Principle of complementarity: Equal numbers of A,T & C,G
3. The base pair (A,T or C,G) is nearly flat, 2-D plane
4. Stacking together forms the double helix shape of DNA
5. Two strains, but one strain (order of the bases) goes one direction & the other strain goes the opposite

• The pairing of the complements leads to the mechanism for copying genetic materials
• Key to the gene's main function: replication & protein synthesis

Replication

• DNA replication or gene-copying
• Each strand of the double helix contains the information necessary to make its complementary strand
• Replication process:

1. DNA two strains pulled apart by a "snipping" enzyme, beginning at a small region called the origin
2. Free nucleotides (a sugar, one base & three phosphate) floating around are attracted to its complement (A to T, C to G) or repelled when not
3. "Clipping" enzyme goes in only direction, puts them together & kicks off the extra two phosphates
4. Disentangling the two new chromosomes

• Unwinding the double helix involves rotations over 8000 rpm
• Principle of complementarity is also essential for making enzymes
• Molecule is the message
• The sequence of DNA must parallel the sequence of the protein
• The sequence of base pairs may be thought of as a series of "words" specifying the order of amino acids in each protein

RNA

• Ribonucleic acid
• The "messenger" molecule copied from DNA (the master code) to translate into amino acids for proteins
• DNA remains inside the nucleus, while the messenger RNA can be transit into the cell cytoplasm to reach the ribosomes to make into proteins
• RNA has ribose sugar
• It is usually single-stranded
• It is much shorter (50~1000 nucleotides) than DNA (millions)
• RNA base pairs:

1. A with U (Uracil) in place of T
2. C with G

• Transcription process:

1. RNA polymerase enzyme pulls apart a certain DNA region
2. Copies along one strand
3. RNA formed is mRNA, messenger RNA
4. The genetic message carried is in groups of three (codons)

Genetic code

• Each codon = a single amino acid
• 1961: Marshall Nirenberg make special mRNA with only "U" (poly-U) to obtain a protein from the amino acid, Phenylalanine
• Genetic code: the meaning of the chains of codons
• Types of codons:

1. 64 possible codons, but only 20 amino acids
2. One codon = one amino acid
3. Some codons are synonyms
4. "Stop" signals: three codons
5. Code is non-overlapping

Proteins made

• Translation from mRNA into proteins involves
• Two additional ingredients:

1. Transfer RNA: tRNA, that has the shape of a cross, with 3 bases (anticodon) at its head & an amino acid at its tail (attached to it by an enzyme that recognises its anticodon)
2. Ribosome: a double ball (small ball & big ball) of about 50 proteins wrapped up with RNA called ribosomal RNA (rRNA); a ribosome has two slots which fit two tRNA snugly

• Protein-making process:

1. mRNA reads DNA sequence & enters cytoplasm - a sea of ribosomes
2. a ribosome binds onto the mRNA located at & near to the codon AUG (always the first codon of every mRNA message)
3. tRNA with complement (Principle of Complementarity) codon UAC & amino acid Methionine attaches to slot 1 of ribosome
4. Ribosome moves down another codon on the mRNA, then another complementary tRNA fits into the second slot of ribosome
5. The first amino acid Methionine is linked to the second amino acid
6. The first tRNA (now without any amino acid) UAC is discarded by ribosome
7. Ribosome moves down another codon & another complementary tRNA fits in with another amino acid
8. The processes continue as the amino acids are chained to form proteins
9. It ends when the ribosome reaches one of the "stop" codon & stops because there are no complementary anticodon for the "stop" codons
10. Protein is freed (whether for structure, enzyme, etc.) & ribosome unbinds

Blue print

• In summary, chromosome encodes sequences for tRNA molecule encodes sequences for mRNA which are translated into protein & sequences for ribosomal RNA
• DNA is the blueprint of all cell's essential parts

PRO & EU

• Eucaryotes/eukaryotes: any cell with a nucleus
• Procaryotes/prokaryotes: bacteria with simpler structure
• Idea: Procaryotes comes before Eucaryotes
• In all life, the genetic code is the same
• Suggesting that all life comes from a common ancestor, in whatever form it was
• Differences between Eucaryotes (EU) & Procaryotes (PRO):

1. Difference 1: EU has porous nucleus membranes to allow RNA & enzymes to pass freely & keep out ribosomes; a perfectly good gene has several sequences called introns such that after transcription, mRNA has to be trimmed of these introns by a complex of protein & RNA called spliceosome; these capping, tailing & trimming do not occur in PRO
2. Difference 2: EU contains more genes (humans 200,000 compared to E.Coli 4,000) such that DNA is wrapped in bundles called nucleosome core; unknowns about the packaging & arrangement of nucleosome cores during cell division (mitosis & meiosis)
3. Difference 3: EU genes contain lots of repetitive DNA, sequences of nucleotides that repeat themselves many times

Virus

• One way to explain the existence of repetitive DNA in EU cells are genetic hitchhikers
• One form is virus
• Viruses are the simplest known living things made of two parts:

1. Nucleic acid
2. Protein coat

• A virus lives as a parasite, invading a host cell & taking over its ribosomes, enzymes & energy
• It injects its DNA or RNA into the host cell
• Retro virus: an RNA virus encoding an enzyme that makes a DNA copy of its RNA & splices it into the host chromosome
• The virus permanently changes the host chromosomes
• AIDS works this way
• Then editing of mRNA may have evolved as a defence against inappropriate sequences stuck into the middle of genes
• Another way of dealing with repetitive sequences: shut those genes down

Mutation & dominance

• Gene mutation results in mistaken amino acid that might be faulty or improved, depending
• Most mutations are recessive or redundant
• A mutation usually causes an inability to make an enzyme
• As such only when both strains have exactly the same mutant genes that mutation becomes phenotype

Co-dominant

• Some alleles are co-dominant: a heterozygote makes both phenotypes
• Example is blood groups

Gene regulation

• Clearly, different genes are active in different cells
• Each cell must have ways to decide which genes to turn on & when
• 1950's: Jacques Monod & Francois Jacob examine E.Coli's ability to digest lactose
• They found:

1. Operon: cluster of genes encoding related enzymes & regulated together
2. Promoter region: at the start of each operon
3. Highly-used enzymes: easy promoter region for RNA polymerase
4. Less used enzymes: difficult promoter region for RNA polymerase

• Repressor: a protein that blocks the action of polymerase & shuts down the entire operation, but release the DNA whenever it catches a lactose
• Attenuation: amino acid Histidinefools ribosome & bumps polymerase off the operon & shuts down the operation
• Jumping genes: genes that create enzymes that flip genes along the chromosome sections (called transposons) to stop & promote activation; common in both eucaryotes & procaryotes; best examples are antibodies - proteins that are defensive weapons attacking bacteria, viruses & other invaders

Genetic engineering

• Rearranging genes for something
• Recombinant DNA: splicing pieces of DNA together to get new DNA
• Gene cloning: replicate gene
• Genes for business: scientists into business
• Experimentation: gene testing on human subjects first conducted in UCLA for thalassemia (inability to make hemoglobin caused by a mistaken "stop" codon of the gene for one of its chains); they failed & received objections from all sides
• Issues: impacts that need to resolved as we find ourselves confronted by our own awesome "powers"