MIT Hierarchical Introductory Biology Concept Framework

1. Biology is based on observational and experimental science.

1-1. We think what we think because we can draw conclusions from the results of controlled experiments.

1-2. An informative experiment is designed to distinguish between hypotheses.

1-3. All experiments must have controls to be informative and interpretable.

1-4. Models based on experimental data should have predictive powers.

1-5. There are often exceptions

 

2. At the molecular level, biology is based on three-dimensional interactions of complementary surfaces.

2-1. All molecules are 3D objects (2D is just a representation).

2-2. Structure of a molecule enables its function.

2-2-1. Structure is a combination of the 3D shape of the molecule and the chemical identities of the different parts of the domains of the molecule. See 11-3.

2-3. Interaction between molecules happens by shape matching/fitting with the use of chemical entities in the faces of the interacting molecules.

2-3-1./2-4-1. Molecules that seem to differ in very minor ways (e.g. phosphorylation) can have drastically different properties if their interactions with other molecules are specific.

2-3-2. Interacting components often combine by self-assembly.

2-4. Altering the specificity of interactions is possible with minor structural modifications.

2-4-1./2-3-1. See above.

2-5. All interactions in a cell happen because of a combination of molecular forces. See 2-2-1.

2-5-1. Covalent bonds are bonds in compounds that result from the sharing of one or more pairs of electrons.

2-5-1-1. The primary structure of macromolecules is held together by covalent bonds. See 11-6-2.

2-5-1-2. The polymerization of macromolecules forms a covalent bond between subunits and releases H₂O.

2-5-2. An ionic bond is an electrical attraction between two oppositely charged atoms (ions) or groups of atoms.

2-5-3. A hydrogen bond is a dipole-dipole interaction between molecules containing hydrogen directly bonded to a small, highly electronegative atom, such as N, O, or F. See 2-6.

2-5-3-1. Secondary structure of proteins and nucleic acid complementary strands are held together by hydrogen bonds.

2-5-4. van der Waals force is the attraction between very closely located neutral molecules, through induced dipoles.

2-5-5. The relative strength of these 4 molecular forces in descending order is: covalent, ionic, hydrogen, and van der Waals.

2-5-6. Hydrophobic groups immersed in water are attracted to each other in order to minimize contact with water molecules and to minimize the reduced entropy resulting at the interface between hydrophobic and hydrophilic domains —Hydrophobic effect. See 2-6-4.

2-6. Many of the physical properties of water are due to hydrogen bonds See 2-5-3.

2-6-1. The magnitude of bond polarity is proportional to the difference in electronegativity between the atoms forming the bond.

2-6-2. Water is a network of hydrogen bonds.

2-6-3. Hydrophilic (water soluble) molecules contain polar bonds or charged atoms, and can form hydrogen bonds with water, thus becoming part of the network.

2-6-4. Hydrophobic (water insoluble) molecules contain non-polar moieties, and need to "hide" from water, which is looking to displace them in order to resume the hydrogen bond network and increase entropy. See 2-5-6.

 

3. The cell is the basic unit of life.

3-1. A cell has all of the machinery necessary to perform metabolism and reproduction.

3-1-1/6-2-1. Before a cell divides, all of its machinery is duplicated.

3-2. A cell is separated by a membrane from the environment (compartmentalized).

3-2-1. A drop of water with all of the same contents as a cell but no membrane will not be able to perform all cellular functions

3-2-1-1. Without a membrane a cell can’t make a physically separate copy of itself because of diffusion.

3-2-2. Membranes are polar on the outside edges and hydrophobic in the middle.

3-2-3. Membranes separate inside from the outside.

3-2-3-1. Vesicle membranes separate things within the cell.

3-2-4. The need to "hide" hydrophobic tails drives membrane and vesicle self-assembly. See 2-5-6.

3-2-5. The hydrophobic core of membranes allows proteins with hydrophobic regions to be embedded in the membrane.

3-3. A virus is not alive because it requires a host cell to perform metabolic functions.

3-3-1. A virus does not have all of the machinery necessary to perform metabolism and reproduction. See 3-1.

3-4. No cell lives in the absence of other cells; cells communicate with and often depend on each other. See 5.

3-5. There are two major categories of cells: those with a nucleus (eukaryotes) and those without a nucleus (prokaryotes).

3-6. There are three major categories of organisms: bacteria, archaea, and eukaryotes. See 4-6.

 

4. All cells share many processes/mechanisms.

4-1. Many metabolic pathways are conserved across evolutionary spectrum (e.g. glycolysis).

4-1-1. Comparing the versions of elements of these pathways across species helps order these species on the evolutionary tree.

4-1-1-1. The DNA sequence of the genes encoding elements of these pathways is better conserved in more closely related species.

4-1-2. Once a cellular function is developed, it is only improved upon if selective pressure is applied. See 11-2-4, 16.

4-2. The same genetic code is used by both prokaryotes and eukaryotes. See 3-5, 7-1.

4-3. All organisms use ATP as their primary energy currency. See 11-6-2.

4-4. Many aspects of eukaryotic cell structure and function have remained unchanged or minimally modified throughout evolution. See 3-5, 4-5, 4-5-1.

4-4-1. chromosomes

4-4-2. nuclear membrane

4-4-3. mitochondria

4-4-4. endoplasmic reticulum

4-5. Basic research on microorganisms is relevant to understanding human cellular biology and human disease.

4-5-1. Studying basic cellular processes in microorganisms has yielded insights into the workings of multicellular organisms. See 4-1, 4-1-2.

4-5-2. Some micro-organisms cause infectious disease in other organisms. See 18-1.

4.6 There are three major categories of cells: bacteria, archaea, and eukaryotes. Some processes are shared between the groups and some are not. See 3-6.

 

5. Cells interact with other cells.

5-1. Each cell communicates with other cells that are either near or far away.

5-2. Cells communicate by releasing physical objects—i.e.molecules— or by binding each other directly. See 2-2, 2-3, 12-3.

5-2-1. Regardless of the mode of communication, the downstream result is the transmission of a signal into the cell receiving the message.

5-2-2. Inside the cell the signal is propagated via the same mechanism of physical interactions. See 2-3.

5-2-2-1. The result of the signal propagation is a change in gene expression. See 6-4-1, 8-2, 14-1-2.

5-3. Groups of cells work together to make tissues and organs. See 18.

5-4. Communities of unicellular organisms share information.

5-5. Organisms communicate information to each other about their environment. See 17.

5-6. Sexually reproducing organisms require other organisms to have offspring. See 6-3, 10-1, 16-1-3.

5-6-1. The exception to the requirement for a sexual partner is self-fertilization. 

 

6. Cells are created from other cells.

6-1. Cells formation by spontaneous generation has never been observed. See 3-2-1.

6-2. As a result of cell division, one cell becomes two.

6-2-1./3-1-1. Before a cell divides, all of its machinery is duplicated.

6-2-2. When eukaryotic cells divide, DNA replication followed by chromosomal segregation in mitosis (2nà 4nà 2n) ensures that the daughter cell has the same genetic information as the mother cell.

6-2-3. The complementary base-pairing of DNA molecules allows for a built-in duplication mechanism. See 9-1-3.

6-2-3-1. Two molecules of DNA are created from one, by semiconservative replication.

6-2-3-2. Each of these new molecules goes to a daughter cell. Therefore, one mother cell gives rise to two daughter cells.

6-2-4. Prior to cell division, all essential cellular machinery is duplicated and segregates into future daughter cells. See 3-1-1/6-2-1.

6-3. In sexual reproduction, two gametes join to form a zygote. See 5-6, 10-1, 16-1-3.

6-3-1. Each gamete carries half the genetic complement of a cell. See 10-1-3.

6-3-1-1. A gamete carries a haploid set of chromosomes. See 10-2-2.

6-4. One cell division can give rise to two cells that will differentiate into two distinct cell types, serving two distinct functions.

6-4-1. Differentiation usually involves the selective reading of a genome rather than a change in the sequence of the genome. See 7-4, 8-2, 11-2-1, 12-7-1, 14-1, 14-1-2, 14-3-1.

6-4-1-1. Two cells that result from one division, and have the same genetic material can have different morphology and behavior due to differentiation— expressing a different set of genes to perform a different function in the organism. See 12-7-1.

6-4-2. Terminally differentiated cells (that are capable of division) can only give rise to cells of the same type as self.

6-4-3. In multicellular organisms, pluripotent (stem) cells have the potential to differentiate into many different cell types.

6-4-3-1. Whole animal cloning seeks to create the original pluripotent cell—an embryo, using the nucleus of a differentiated cell. See 13-3-1-6.

 

7. DNA is the source of heritable information in a cell.

7-1. The amino acid sequence of proteins is encoded in DNA. See 8-1, 8-1-2, 8-2.

7-1-1. Sets of three letters in the nucleic acid alphabet (that consists of 4 letters) specify one letter in the protein alphabet (that consists of 20 letters). See 8-1-3.

7-1-1-1. 64 triplet codons: ATG initiating methionine, 3 Stop codons, 60 other codons for the remaining 19 amino acids

7-2. Information is encoded in DNA, using different languages that are recognized by different machinery.

7-2-1. DNA encodes when a gene will be expressed or not

7-2-1-1. DNA sequence: promoter, operator, enhancer

7-2-1-2. Protein machinery: activator, repressor, transcription factors

7-2-2. DNA encodes the point at which replication begins

7-2-2-1. DNA sequence: origin of replication (ori). See 13-3-1-3.

7-2-2-2. Protein machinery: origin recognition complexes

7-2-3. t-RNA acts an adaptor to translate the nucleotide sequence into an amino acid sequence. See 7-1.

7-2-3-1. The anticodon of a t-RNA is complementary and antiparallel to the codon it binds. See 7-1-1-1.

7-2-3-2. Ribosomes are responsible for bringing the mRNA and t-RNA together and catalyzing the formation of peptide bonds.

7-2-4. DNA encodes the information to properly segregate chromosomes during cell division.

7-2-4-1. DNA sequence: centromere.

7-2-5. DNA encodes the cellular address of each protein. See 12-7-2-1.

7-2-5-1. DNA sequence encodes: nuclear localization signal, mitochondrial uptake sequence, signal sequence, and transmembrane domain.

7-2-5-2. Protein machinery: receptors bind these amino acid sequences and localize proteins accordingly.

7-2-6. DNA encodes: restriction endonucleases recognition sites. See 13-3-1-5, 13-3-4.

7-3. When DNA is mutated, the information it contains may be changed.

7-3-1. Because DNA can encode amino acid sequences, the structure and therefore the function of proteins may be changed. See 2-2, 7-1, 8-1-4.

7-4./8-1-2. Segments of DNA that contain all of the information to encode the sequence of a product and regulate its expression are called genes. See 8-1-2-1.

7-4-1. The DNA that comprises an organism’s genome is organized into chromosomes. See 8-7.

 

8. A gene is the functional unit of heredity.

8-1. A gene is composed of DNA and

8-1-1. A gene can encode when, where, and what polypeptide should be made.

8-1-2./7-4. Segments of DNA that contain all of the information to encode the sequence of a product and regulate its expression are called genes.

8-1-2-1. A gene that encodes a protein consists of a regulatory region, a promoter, a start codon, a stop codon, the intervening polypeptide encoding sequence and a transcriptional terminator. See 7-2.

8-1-3. Genes are encoded in DNA using a 4 letter alphabet. See 7-1, 8-6.

8-1-4. If DNA is mutated within the coding or regulatory regions of a gene, a different product may be made, no product may be made, or a product may be made constitutively. See 7-3, 16-1-1, 16-2.

8-1-2-1. Any of these changes may lead to a change in the phenotype of the organism. See 8-5.

8-2. Which genes are expressed at a given time is determined by the integration of internal and environmental signals received by a cell. See 6-4-1, 11-2-1, 11-2-2, 12-7-1.

8-3. Factors determining traits (genes) are inherited as discrete entities.

8-3-1. Even though the genes are strung together on continuous pieces of DNA (chromosomes) the traits they encode are inherited discretely.

8-3-2. Genes located nearer to each other on chromosomes are more likely to be inherited together. See 8-7-1.

8-4. An allele is a particular version of a gene.

8-4-1. Alleles may differ from each other by as little as one basepair.

8-5. A phenotype is a trait, a genotype is the set of alleles conferring that trait.

8-5-1. Genetic analysis is done by observing phenotypes of successive generations of crosses to elucidate genotype.

8-6. Dominant and recessive refer to phenotypes not genotypes.

8-6-1. A phenotype can be described as recessive, dominant, codominant, or incompletely dominant only with respect to another phenotype.

8-7. Chromosomes are made up of a set of physically linked genes. See 7-4-1, 8-3-1.

8-7-1. Recombination of genes occurs because of the physical swapping of pieces of chromosomes (during meiosis). See 10-2-3-1.

8-7-1-1. The recombination frequency between two genes is equal to the proportion of offspring in which a recombination event occurred between the two genes during meiosis.

8-7-1-1-1. If the recombination frequency between two genes is less than 50% then the genes are linked.

8-7-1-1-2. If the recombination frequency between two genes is 50% then the genes are not linked.

8-7-1-1-2-1. The recombination frequency between two genes cannot be greater than 50%. Random assortment of genes generates 50% recombination.

8-7-1-1-3. The recombination frequency (genetic distance) between two genes is often to correlated to the physical distance between the two genes.

8-8. By identifying the gene that differs from wildtype in a mutant displaying a phenotype of interest we can determine which gene is responsible for that phenotype. See 13-3-3.

8-8-1. Complementation tests can be used to determine whether two mutants carry mutations in the same gene or in different genes.

8-8-1-1. A complementation test can be performed by mating two mutants that display the same phenotype.

8-8-1-2. If two mutants complement each other (an organism that contains both mutations will have a wildtype phenotype) then the two mutations are not in the same gene (they do not belong to the same complementation group).

8-8-1-3. If two mutants do not complement each other (an organism that contains both mutations does not have a wildtype phenotype) then the two mutations are in the same gene (they belong to the same complementation group).

8-8-2. If gene A is epistatic to gene B then the AB double mutant has the phenotype conferred by the allele of gene A.

8-8-2-1.When ordering genes in biochemical pathways based on feeding requirements for growth, the observed phenotype is conferred by the gene that comes later in the pathway.

8-8-2-2.When ordering genes in biochemical pathways based on the build up of intermediates the observed phenotype is conferred by the gene that comes earlier in the pathway.

8-9. Inheritance modes in humans fall into 6 major categories

8-9-1. Autosomal dominant

8-9-2. Autosomal recessive

8-9-3. X-linked dominant

8-9-4. X-linked recessive

8-9-5. Y-linked

8-9-6. Mitochondrially inherited

8-10. The pattern of affected individuals can help determine the mode of inheritance of a phenotype. Things to consider are:

8-10-1. Ratio of male/female affected

8-10-2. Percentage of offspring affected

8-10-3. Mother or father of affected was affected

8-10-4. Skips generations?

8-10-5. Carriers?

8-11. Genes can be transferred not only from parent to offspring (vertically), but also from one individual to another (horizontally). See 16-1-2-2.

8-11-1. Viruses can transfer genes from one host to another.

8-11-2. During bacterial conjugation, genes can be transferred from one individual to another.

 

9. The structure of DNA dictates the mechanism of the production of nucleic acids and proteins.

9-1. DNA is usually double-stranded.

9-1-1. The two strands are complementary.

9-1-1-1. Each DNA strand serves as a template for synthesis of a new complementary strand of DNA in replication.

9-1-1-2. For each gene, one strand of DNA serves as a template for synthesis of a complementary RNA strand in transcription.

9-1-2. The two strands are antiparallel.

9-1-2-1. The antiparallel nature of nucleic acids has consequences for replication, transcription, translation. See 9-2, 9-3.

9-1-3. Complementary base pairing allows for the semi-conservative duplication mechanism. See 6-2-3.

9-2. Nucleic acids are polymerized in only one direction (5’ to 3’).

9-2-1. Because nucleic acids are polymerized 5’ to 3’, each replication fork will have a leading strand and a lagging strand (composed of Okazaki fragments).

9-2-2. Mechanism of nucleic acid polymerization dictates the choice of template for the newly created strands, as well as the choice of PCR primers, and makes sequencing by polymerization possible. See 13-4.

9-2-3. DNA polymerase can fix errors that are made during replication. See 16-2-3.

9-2-3-1. An exonuclease activity of DNA polymerase removes incorrect nucleotides in the 3’ to 5’ direction (polymerase moves backwards).

9-3. In vivo proteins are polymerized from the amino terminus to the carboxyl terminus (N to C).

9-3-1. Directions of polymerization of nucleic acids and proteins are mechanistically connected. See 9-2.

9-3-2. In prokaryotes, translation of a protein begins before transcription of an mRNA is completed. Therefore, translation has to proceed N to C.

 

10. Sexual reproduction is a powerful source of variation.

10-1. Sexually reproducing diploid organisms get one copy (allele) of each gene from each parent and pass one allele on to each of their offspring at random. See 8-3.

10-1-1.One exception is sex-chromosome encoded genes in males.

10-1-2. Alleles are passed on to offspring without respect to the phenotype they confer.

10-1-3. An individual only passes one allele of each gene to its offspring. See 6-3-1.

10-1-3-1. Exception in 10-1-1 here applies for males and females.

10-1-3-2. The phenotype of an individual depends on the combination of alleles from both parents.

10-1-3-2-1. See exception in 10-1-1.

10-1-4./16-4-1.Only mutations in germ line cells will be passed on to the offspring. See 6-3, 10-2-2.

10-1-5. Somatic mutations are passed on to any descendants of the mutated cell within the organism, and can cause non-inherited disease.

10-2. Diversity is introduced in gamete formation.

10-2-1. Sexual reproduction allows for great diversity and fast change (through bringing together genetic information from two parents). See 6-3.

10-2-2. Gamete production in meiosis (2nà 4nà 2nà n) allows for reshuffling of parental genetic information through independent segregation of chromosomes. See 10-1-2.

10-2-3. Recombination—the exchange of parts of chromosomes between homologous pairs of chromosomes—increases the rate of reshuffling of parental genetic information compared to 10-2-2 alone. See 8-7-1.

10-2-3-1. Recombination occurs during meiosis, after the DNA has been duplicated and the homologous chromosomes are lined up.

 

11. Life processes are the result of regulated chemical reactions.

11-1. Life obeys all of the laws of chemistry and physics.

11-1-1. Both uni- and multi-cellular organisms obey the laws of thermodynamics.

11-2. All cellular processes consist of changes in chemical interactions

11-2-1. Not all reactions need to happen in a cell at the same time. See 6-4-1, 14-1.

11-2-2. To respond to changes in the environment appropriately, chemical reactions in the cell need to be regulated. See 14-1-2.

11-2-2-1. Regulation can be at the level of regulating the reaction itself or of regulating whether reactants and enzymes are present. See 14.

11-2-2-2. Regulation may be abolished by mutations in cis or trans elements. See 7-3, 8-1-4, 14-2.

11-2-3. All binding is dynamic—the difference is relative time spent in the bound vs. unbound state.

11-2-4. Cellular interactions only evolved to be as energetically efficient as necessary based on selection. See 4-1-2, 16-3.

11-3. All biological macromolecules are created by chemical reactions involving monomers.

11-3-1. All these polymers are made by dehydration synthesis, which forms covalent bonds and releases water. See 2-5-1-1.

11-3-1-1. Building blocks of proteins are amino acids.

11-3-1-1-1. Dehydration synthesis forms rigid peptide bonds.

11-3-1-2. Building blocks of nucleic acids are nucleotides.

11-3-1-2-1. Dehydration synthesis forms a bond between the 3’ OH group of the chain and the phosphate attached to the 5’ group of the nucleotide being incorporated. See 9-1.

11-3-1-3. Building blocks of polysaccharides are monosaccharides.

11-3-1-4. Building blocks of lipids are fatty acids and glycerol.

11-3-2. The complexity necessary for life is encoded in the sequence of monomers incorporated into the polymer molecule.

11-4. ∆G⁰ is a thermodynamic property—an inherent characteristic of a reaction regardless of starting conditions.

11-4-1. ∆G tells whether a reaction is energetically favorable under a set of conditions, not whether it will go spontaneously.

11-4-2. Activation energy of a reaction is the energetic barrier between the reactants and the products. With a large activation energy, a reaction may not occur spontaneously in a short time (cellular time scale). See 11-5-2.

11-4-2-1. Activation energy of a reaction is determined by the highest energy intermediate in the reaction.

11-5. Life could not exist without enzymes to speed up reactions. See 11-4-1.

11-5-1. Most reactions critical for life are not spontaneous or rapid at cellular pH and temperature.

11-5-2. Enzymes speed up a reaction by lowering the activation energy. See 11-7-2.

11-5-2-1. Enzymes speed up both the forward and the reverse reaction.

11-5-2-2. The direction in which reaction actually proceeds can be influenced by the concentration of reactants and products.

11-5-3. Enzymes (catalysts) cannot make energetically unfavorable reactions happen.

11-5-4. Catalysts begin and end a reaction physically unaltered.

11-5-5. A pathway can be regulated through allosteric regulation of a second binding site on the enzyme. See 14-3-2.

11-6. All cells use the same common currencies to drive energetically unfavorable reactions.

11-6-1. Having common energy/electron storage currency allows the cell to couple unfavorable reactions to favorable ones, thus driving them forward.

11-6-2. ATP is the common energy currency.

11-6-2-1. Energy is stored in the phosphate bonds.

11-6-2-2. ATP is created through glycolysis or the electron transport chain (ETC) in aerobic respiration.

11-6-3. NADH is the common electron currency.

11-6-3-1. The lone pair of electrons is stored on the N.

11-6-4. Cells take incremental steps to derive energy from favorable reactions so as not to waste energy.

 

12. Proteins perform many varied functions in a cell.

12-1. Proteins can be enzymes that catalyze reactions. See 11-5, 12-2-2.

12-1-1. Enzymes are critical to metabolic processes.

12-2. Proteins can interact with each other and nucleic acids to regulate the production of proteins and nucleic acids. See 14-3-1.

12-2-1. Proteins can bind regulatory elements in DNA and act as activators or repressors of transcription.

12-2-2. DNA and RNA polymerases can bind regulatory elements in DNA and catalyze the production of nucleic acids. See 12-1.

12-3. Proteins can detect and transmit signals from the outside of the cell. See 5-2.

12-3-1. Growth factor receptors on the cell surface bind ligands and transmit the information that a cell should grow and divide.

12-4. Proteins can provide structure and shape to a cell or part of a cell.

12-4-1. The cytoskeleton is made of several kinds of proteins.

12-5. Proteins can transport things around in a cell.

12-5-1. Microtubules, microfilaments, and motors move vesicles from one location to another in the cell.

12-6. Other molecules (nucleic acids, sugars, lipids, small ligands) all interact with proteins to accomplish their functions (including the functions listed above). See 7-2.

12-7. Cells make thousands of different proteins simultaneously.

12-7-1. Cells having identical genetic information can express somewhat different sets of proteins, resulting in different phenotypes. See 6-4-1, 11-2-1.

12-7-2. Mutant phenotypes can result when proteins are not targeted to their respective locations within or outside of the cell.

12-7-2-1. The cellular machinery is able to target a protein to its intended location based on a segment of amino acids found within the protein sequence. See 7-2-5.

 

13. Recombinant DNA technology allows scientists to manipulate the genetic composition of a cell.

13-1. Recombinant DNA is a set of tools that allows scientists to move between genetics, biochemistry and molecular biology – allowing us to determine how the parts of a cell or organism work.

13-2. Many of the techniques and reagents used in recombinant DNA technology are adaptations of processes that exist in nature.

13-3. Recombinant DNA techniques can be used to help identify the gene responsible for a trait.

13-3-1. Cloning DNA means to isolate a gene or fragment of DNA away from the other DNA of an organism and be able to propagate this piece.

13-3-1-1. A DNA fragment is inserted into a plasmid for propagation.

13-3-1-2. Plasmids are naturally occurring small pieces of DNA that can replicate in micro-organisms.

13-3-1-3. Plasmids and vectors have origins of replication which allows for replication in micro-organisms. See 7-2-2-1.

13-3-1-4. One can screen or select for the presence of a vector.

13-3-1-5. A plasmid or a vector has a restriction site recognized by a restriction enzyme, where a piece of DNA can be inserted. See 7-2-6, 13-3-4.

13-3-1-6. Cloning DNA is not the same as whole animal cloning in which a genetically identical animal is produced. See 6-4-3-1.

13-3-2. A library is a set of vectors containing DNA inserts that collectively represent all of the DNA in a genome or all of RNAs expressed in a cell.

13-3-2-1. Each vector has only one piece of DNA or cDNA, but collectively the vectors contain all of the information.

13-3-3. To find the piece of DNA, RNA you are interested in, you must devise a way to screen a library for an organism containing that nucleic acid.

13-3-3-1.One can screen a library by selecting for only the organisms of interest (those with a desired property survive).

select by function: complementation (drug selection, auxotrophy selection)

13-3-3-2. One can screen a library by screening all organisms for an indicator (usually visual) other than survival.

screen by sequence: hybridization (filter lift, Southern, northern)

13-3-4. Restriction enzymes (naturally occurring in bacteria) make it possible to cut DNA at predetermined sequences without damaging the DNA sequence. See 7-2-6, 13-3-1-5.

13-4. PCR allows the exponential amplification of a particular DNA sequence.

13-4-1. Application of replication enzymes

13-4-2. Primer choice is dictated by the mechanisms of nucleic acid polymerization. See 9-2-2.

13-4-3. DNA fingerprinting uses PCR of specific variable sequences to eliminate suspects or analyze family relationships.

13-5. Homologous recombination can be used to introduce a modified gene into an organism

13-5-1. This is an application of the mechanism of recombination used in meiosis that is dependent on sequence homology. See 10-2-3-1.

13-5-2. Homologous recombination can be used to introduce a new gene or knock out a gene.

 

14. The expression of genes is regulated.

14-1. Not all genes need to be expressed at all times. See 6-4-1, 11-2-1.

14-1-1. Gene products are regulated in their timing and abundance.

14-1-2. Expression of some gene products needs to be regulated in response to external stimuli (e.g. change in available nutrients) or internal processes (e.g. cell cycle progression). See 11-2-2.

14-1-3. Levels of protein can also be regulated by abundance and stability of the mRNA transcript or by post-translational modifications.

14-2. RNA Polymerase and regulator proteins (trans-acting elements) interact with regulatory regions (cis-acting elements) by binding to either promote or prevent transcription. See 2, 11-2-2-2, 16-2-1-2.

14-2-1. Cis-acting elements are sequences of DNA. See 7-2, 8-1-2.

14-2-1-1. Defects in cis-acting elements cannot be repaired by introducing another copy of the element into the cell (e.g. RNA polymerase binds the promoter and begins transcription only of physically connected DNA).

14-2-1-2. Mutations is cis-acting elements will affect only the protein encoded by the gene where the cis-acting element is located.

14-2-2. Trans-acting elements are gene products (and small molecules). See 7-1.

14-2-2-1. Recessive defects in trans-acting elements can be repaired by introducing another copy of the gene encoding the elements into the cell.

14-2-2-1. Mutations in trans-acting elements will affect the expression of all genes whose transcription is regulated by the trans-acting element.

14-3. Components of processes that work together are often regulated together.

14-3-1. It is energetically favorable to co-regulate the expression of genes that encode proteins involved in a pathway or process.

14-3-1-1. Co-regulated genes can be organized into operons or share common transcription factors and their consensus binding sites.

14-3-2. Allostery allows a pathway to regulate itself by regulating the speed of the key reaction.

14-3-2-1. Allostery is the modulation of the affinity of a site for a substrate by a regulatory molecule binding at another site. See 11-5-5.

14-3-2-1-1. In case of overabundance of the pathway substrate, allosteric binding to the key enzyme can increase the speed of reaction.

14-3-2-1-2. In case of overabundance of the pathway product, allosteric binding to the key enzyme can decrease the speed of reaction or inhibit it altogether. 

 

15. All carbon-containing biomass is created from CO₂.

15-1. All organisms utilize organic nutrients, in particular organic carbon, to live and grow—accumulate biomass.

15-2. Someorganisms are able to convert inorganic carbon in CO₂ into organic carbon through photosynthesis.

15-2-1. Photosynthesis harvests the energy of sunlight to drive the electron transport chain (ETC) reaction to create ATP and glucose. See 11-6-2-2.

15-2-2. In order to live and increase in mass (grow) non-photosynthetic organisms need to consume photosynthetic organisms, or organisms that consumed photosynthetic organisms, to get organic carbon.

15-2-3. Chemosynthetic organisms (or organisms that eat chemosynthetic organisms) are the exception to this dependence on photosynthetic organisms.

15-3. Aerobic respiration consumes O₂ and releases CO₂ into the atmosphere.

15-4. Photosynthesis consumes CO₂ and releases O₂ into the atmosphere.

15-5. If Photosynthesis = Respiration, the global carbon cycle is in equilibrium and no changes to the environment are introduced.

15-5-1. Burning fossil fuel and deforestation create a situation where Respiration > Photosynthesis.

15-5-1-1. When Respiration > Photosynthesis, there is a net increase in the levels of in the CO₂ atmosphere, resulting in global warming. 

 

16. Populations of organisms evolve because of variation and selection.

16-1. Mutation, recombination, and exual reproduction are genetic sources of variation.

16-1-1. Mutation is a heritable change in DNA sequence of an organism. See 16-2.

16-1-1-1. Mutations may be caused by environmental factors or errors in DNA replication and repair. See 16-2-2, 16-2-3, 16-2-4.

16-1-2. Recombination occurs during meiosis, making new sets of alleles. See 8-7-1, 10-2-3.

16-1-2-1. If recombination occurs within homologous genes, new alleles can be formed.

16-1-2-2. New genes can arise as a result of horizontal transfer or acquisition from or by an infectious agent. See 8-11.

16-1-3. Sexual reproduction generates diversity by bringing together genetic information from two individuals. See 5-6, 6-3, 10.

16-2. Mutations can result in a change in phenotype.

16-2-1. Mutations can cause a change in polypeptide sequence or in gene expression. See 7-3, 8-1-1, 8-1-2.

16-2-1-1. Mutations occurring within the coding sequence of a gene may result in a change in mRNA and polypeptide sequence.

16-2-1-2. Mutations in a regulatory element (cis-acting) or a regulatory protein (trans-acting) may result in a change in gene expression. See 8-1-4, 11-2-2-2, 14-2.

16-2-2. Mutation can happen with every round of replication and cell division.

16-2-3. DNA Polymerases and their repair subunits are responsible for the largely faithful replication of DNA.

16-2-4. There are DNA repair mechanisms to limit the mutation rate but they are not perfect.

16-2-4-1. Decreasing fidelity of DNA replication or repair leads to increased appearance of mutant phenotypes.

16-2-4-2. Increased fidelity of DNA replication or repair may lead to a decreased generation of phenotypic variation.

16-2-5. New genes (and phenotypes) can arise as a result of copying and then mutating existing genes within a genome. See 8-11, 16-1-2-2.

16-2-6. New genes (and phenotypes) can arise as a result of combining parts of previously existing genes in novel ways.

16-3. Selection occurs on the level of the individual.

16-3-1.The environment imposes selective pressure on individuals for survival and fertility.

16-3-1-1. Competition for resources is a selective pressure.

16-4. Thousands of genes are passed from parents to offspring, almost all without new mutations. See 16-2-4.

16-4-1./ 10-1-4. Only mutations in germline cells will be passed on to the offspring. See 10-1-3.

16-4-2. Mutations in the somatic cells of an organism will not be passed to its offspring.

16-5. Evolution proceeds without a goal, it is a random process. See 17.

 

17. Organisms and the environment modify each other.

17-1. The environment places selective pressure on organisms—selection favors "mutants" that are better able to survive in the environment. See 4-1-2, 11-2-4, 16-3-1.

17-1-1. e.g. The ability to fix CO₂ into glucose arose in response to the selective pressure of limited abiotic synthesis of organic nutrients.

17-1-2. H₂S was originally used as an electron source, but it became limiting as organisms proliferated. See 17-2-1.

17-2. The products of organisms’ life cycle return to the environment, modifying it.

17-2-1. e.g. In response to the limited supply of H₂S, organisms developed the ability to use H₂O instead of H₂S as the source of electrons for oxygenic photosynthesis, resulting in release of O₂ into the environment, over time increasing O₂ in the atmosphere from 0% to 21%. See 17-1-2.

 

18. In multicellular organisms, multiple cell types can work together to form tissues which work together to form organs.

18-1. The immune system protects a host from foreign invaders.

18-1-1. We know this because:

18-1-1-1. Vaccination (natural and clinical) prevents subsequent disease from the same pathogen

18-1-1-2. Immunodeficiencies lead to higher levels of infection.

18-1-1-3. Immune evasive strategies adopted by pathogens lead to long lasting infections.

18-1-2. The innate immune system prevents initial infection

18-1-2-1. Innate immunity consists of barriers, mucus, and phagocytic cells.

18-1-2-2. Innate immunity is not specific, it is not diverse, does not display memory, and does not distinguish between self and nonself. See 18-1-3.

18-1-3. The acquired immune system is specific, displays memory, is diverse and distinguishes between self and non self. See 18-1-2-2.

18-1-3-1. The immune system displays specificity because a B cell or a T cell recognizes only one (or a limited set of) epitope(s).

18-1-3-2. The immune system displays memory. The second time the acquired immune system encounters an antigen, the response is faster and stronger.

18-1-3-2-1. Exposure to the vaccine leads to the formation of memory cells that are activated upon encountering the pathogen.

18-1-3-2-2. Booster shots refresh and enhance these memory cells.

18-1-3-3. The rearrangement of DNA segments of the TCR and BCR (Immunoglobulin) genes generates immunological diversity.

18-1-3-3-1. The joining during rearrangement is "sloppy" providing more diversity.

18-1-3-3-2. Rearrangement provides many more BCR and TCR coding sequences than there are original genes in the genome.

18-1-3-3-3. These rearrangements make the T and B cells unique in that they will each have slightly different DNA than any other cell in the body.

18-1-3-3-4. Activated B cells undergo somatic hypermutation to create further diversity.

18-1-3-4 The immune system distinguishes between self and nonself.

18-1-3-4-1. Therefore autoreactive T and B cells are normally either deleted or silenced.

18-1-3-4-2. Autoimmune disease results when autoreactive B or T cells are not eliminated or inactivated.

18-1-4. The humoral arm of the immune system targets antigens in extracellular space.

18-1-4-1. The humoral arm consist of B cells, antibodies (Abs) and helper T cells.

18-1-4-1-1. Membrane bound Abs on the surface of B cells bind specific antigens and mediate their endocytosis by B cells.

18-1-4-1-2. Protein antigens endocytosed by B cells are degraded and presented on MHC class II molecules.

18-1-4-1-3. A helper T cell that recognizes an MHC/peptide complex presented by a B cell will activate that B cell.

18-1-4-1-3-1. B cell activation leads to clonal expansion and the generation of plasma cells and memory cells.

18-1-4-2. Antigens are recognized directly by Abs (and need not be protein).

18-1-4-3. HIV infects T helper cells and leads to AIDS by severely impairing the acquired immune response.

18-1-5. The cellular arm of the immune system targets infected host cells.

18-1-5-1. The cellular arm consists of killer T cells.

18-1-5-2. Antigens are recognized by TCRs as peptides presented in the context of MHC class I molecules.

18-2. Development of a multicellular organism from a single cell occurs stepwise. See 6.

18-2-1. Cells arise from a single cell and become different because of the integration of internal and environmental signals received by the cell. See 5-2, 6-4-1, 8-2.

18-2-1-1. Internal signals (determinants) usually function cell-autonomously.

18-2-1-1-1. Determinants are usually proteins inherited by the daughter cell from the mother cell in the previous round of cell division.

18-2-1-2. Environmental signals are usually the result of cell-cell interactions. See 5-2.

18-2-1-2-1./5-2-2-1. The result of signal propagation is a change in gene expression. See 6-4-1, 8-2, 14-1-2.

18-2-2. Development of a multicellular organism is a process consisting of a number of ordered steps.

18-2-2-1. Development starts with the increase in cell number.

18-2-2-1-1. The increase in cell number is balanced with controlled cell death.

18-2-2-2. Development includes increase in the number of cell types.

18-2-2-3. Development includes organization of cell types into tissues and organs.

18-2-2-4. In normal development, tissues and organs are correctly positioned.

18-2-2-5. In normal development, tissues and organs are correctly shaped.

18-2-3./6-4. One cell division can give rise to two cells that will differentiate into two distinct cell types, serving two distinct functions. And all 6-4 subparts.

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