| alkaptonuria | his is a non-fatal disorder where a person’s urine turns black because they cannot break down a molecule called alkapton (which, in normal people without the disorder, gets broken down into other, colorless molecules) |
| Sir Archibald Garrod, | a British medical doctor, was the first to suggest that genes were connected to enzymes. the first to have linked genes with the enzymes that carry out metabolic reactions. |
| “inborn error of metabolism,” | are rare genetic (inherited) disorders in which the body cannot properly turn food into energy. The disorders are usually caused by defects in specific proteins (enzymes) that help break down (metabolize) parts of food. |
| "one gene-one enzyme” hypothesis. This hypothesis has undergone some important updates since Beadle and Tatum | 1. Some genes encode proteins that are not enzymes. Enzymes are just one category of protein. There are many non-enzyme proteins in cells, and these proteins are also encoded by genes.
2. Some genes encode a subunit of a protein, not a whole protein. In general, a gene encodes one polypeptide, meaning one chain of amino acids. Some proteins consist of several polypeptides from different genes
3. Some genes don't encode polypeptides. Some genes actually encode functional RNA molecules rather than polypeptides! |
| core idea for one gene-one enzyme is | that a gene typically specifies a protein in a one-to-one relationship |
| Genetics | is the study of inherited traits, including those partially influenced by environment |
| Genomics | is the study of all the genes in an organism to
understand their molecular organization,
function, interaction, and evolutionary history |
| Genes | are the basic elements of heredity |
| Gregor Mendel | The existence of genes was first suggested by the work of Gregor Mendel in 1866 |
| Classical genetics | is the approach to the study of genetics through analysis of the offspring of matings |
| Friedrich Miescher | discovered DNA in leukocytes in 1869 |
| Molecular genetics | is the analysis of differences between species through the study of DNA itself |
| 1870s | The importance of cell nuclei was recognized when it was observed that they undergo fusion in fertilization of male and female gametes |
| 1900s | The importance of chromosomes was deduced from their „splitting“ behavior during cell division and their constant number characteristic for every species |
| Early 20th century | chromosomes contain DNA and protein
The kinds of protein present differ by cell type
DNA was thought to lack the chemical diversity needed for the genetic material
The diversity of proteins was the reason for the belief that they are the genetic material
This was proven wrong in a series of experiments |
| Frederick Griffith (1928) | he demonstrated that
the genetic material can be transferred from living R cells into killed S cells made them able again to cause the illness in mouse. |
| Avery, MacLeod and McCarty (1944) | showed that the substance causing the transformation
of R cells into S cells was DNA, so that DNA is the genetic material. |
| Hershey and Chase, the „blender“ experiment (1952) | experiment demonstrating that DNA is the active material in bacterial transformation. |
| James Watson and Francis Crick (1953) | Right-handed (B-form) DNA structure
Double-stranded molecule
Duplex polarity and base complementarity (Watson-Crick base-pairing) |
| Three conclusions on the properties of DNA: | DNA is capable of replication through complementary base pairing
The order of bases in a DNA molecule is the source of variation
Mutations arise from mistakes in copying DNA |
| Proteins | are made according to instructions given in DNA sequence |
| Variety functions of Proteins | Trafficking
Structure
Signalling and receptor molecules
Metabolic processes
Enzymatic role |
| Enzymes | were first defined as proteins by Emil Fischer in 1900 and led to define inborn errors of metabolism |
| The S type of S. pneumoniae | synthesizes a gelatinous capsule composed of
complex carbohydrate (polysaccharide) appear large glistening and smooth capable of causing illness |
| The R strains of S. pneumoniae are | unable to synthesize the capsular polysaccharide and that's why they look small and rough not causing illness |
| The R strain of the bacterium does not
cause pneumonia, because | without the capsule
the bacteria are inactivated by the immune system of the host. |
| bacteriophage, | bacteria-eater |
| DNA contains | phosphorus but no sulfur |
| most proteins contain | sulfur but no phosphorus |
| In the Watson-Crick structure | DNA consists of two long chains of subunits, each twisted around the other to form a double-stranded helix. |
| The double helix is right-handed, meaning | DNA is moving in clockwise direction |
| The subunits of each strand are | nucleotides |
| DNA is running in which directions | opposite directions from 5'-3' or from 3'-5' |
| why proteins are important | What is created from the complex and diverse DNA codes is protein, a class of macromolecules that carries out most of the biochemical activities in the cell. |
| Archibald Garrod | Garrod worked with patients who had metabolic diseases and saw that these diseases often ran in families. |
| Griffith's Experiment | studied on streptococcus pneumonia which is bacteria capable of causing pneumonia in mouse ex. When SP is grown in medium it can grow in two different strains. 1st is R strain and S strain.
1. Injecting solution of living S cells of SP to mouse, developing pneumonia and killed the mouse. When blood was taken and grown on nutrient medium S cells could be seen injected previously
2. Injecting solution of living R strain cells of SP to mouse, didn't develop pneumonia and the mouse was alive. When blood was taken and grown on nutrient medium R cells could be seen injected previously
3. Injecting solution of heat killed S cells in which cells were completely dead and inactivated unable to cause illness, of SP to mouse, didn't develop pneumonia and the mouse was alive. When blood was taken and grown on nutrient medium nothing could be seen.
4. Injecting solution of living R cells + heat killed S cells of SP to mouse, develop pneumonia and the mouse was dead. When blood was taken and grown on nutrient medium mixture of living R cells and S cells. |
| Structure of DNA was debated | James Watson and Francis Crick-stated that DNA is double stranded molecule
Franklin
Wilkins |
| why James and Francis were important | had amazing X-ray images of DNA but they weren't sure how to understand the images. Their papers were full of disagreement or confusions about DNA structure being double or triple stranded molecule. Duplex or triplex molecule. |
| why Linus Pauling was wrong | phosphate groups are negatively charged and they reject each other its impossible for them to come together in the core of the DNA. |
| Explain what happens in alkaptonuria and why there is a problem and what is this problem | It occurs when your body can’t produce enough of an enzyme called homogentisic dioxygenase (HGD). This enzyme is used to break down a toxic substance called homogentisic acid. When you don’t produce enough HGD, homogentisic acid builds up in your body. People with alkaptonuria also have urine that turns dark brown or black when it’s exposed to air |
| Alkaptonuria is caused by a mutation on your which gene or which gene will be inactive | homogentisate 1,2-dioxygenase (HGD) gene |
| explain what is PKU | Phenylketonuria (PKU) is a rare genetic condition that causes an amino acid called phenylalanine to build up in the body.
Phenylalanine hydroxylase is an enzyme your body uses to convert phenylalanine into tyrosine, which your body needs to create neurotransmitters such as epinephrine, norepinephrine, and dopamine. PKU is caused by a defect in the gene that helps create phenylalanine hydroxylase. When this enzyme is missing, your body can’t break down phenylalanine. This causes a buildup of phenylalanine in your body. |
| which disease has much more severe consequence | PKU |
| Beadle and Tatum (1940s) were interested in and question about what | interested to find out what would happen as consequences of inducing different mutations to Neurospora crassa. They questioned If these spores were irradiated by X ray or Uv light was it going to be possible that will affect their metabolism in a way they would need something additional grow except those 3 components. |
| Red mold can be cultivated easily only with 3 component | sugar, salt and biotin. |
| Why did Beadle and Tatum chose to study with Neurospora crassa | had a fast and convenient life cycle, one with both haploid and diploid phases that made it easy to do genetic experiments |
| support for growth and developmental of Neurospora crassa which medium is used and why | the cells could grow on minimal medium, a nutrient source with just sugar, salts, and one vitamin (biotin). That's because Neurospora has biochemical pathways that turn sugar, salts, and biotin into all the other building blocks needed by cells (such as amino acids and vitamins). |
| Beadle and Tatum (1940s) studies on Neurospora crassa experiment | Beadle and Tatum exposed Neurospora spores to radiation (x-ray, UV, or neutron) to make new mutations. The treated spores were used to start the sexual cycle in fruiting bodies. After any pair of cells and their nuclei undergo fusion, meiosis takes place almost immediately and results in eight sexual spores (ascospores) included in a single ascus. These are removed individually grew them individually in test tubes containing complete medium. Once each spore had established a growing colony, a small piece of the colony was transferred into another tube containing minimal medium. |
| What did Beadle and Tatum identified | identified new mutations that each caused a block in the metabolic pathway
for the synthesis of some needed nutrient, and showed that each of these blocks corresponded to a defective enzyme needed for one step in the
pathway. |
| One class of arginine-requiring mutants, designated Class I, | was able to grow in minimal medium supplemented with either ornithine, citrulline, or arginine. |
| . Other mutants, designated
Class II | were able to grow in minimal medium
supplemented with either citrulline or arginine,
but not ornithine. |
| A third class, Class III, | was able to grow only in minimal medium supplemented with arginine |
| one gene, one enzyme hypothesis | idea that each gene encodes a single enzyme. |
| To figure out which metabolic pathway was "broken" in each mutant, Beadle and Tatum performed 3 Steps | First, they grew each mutant on minimal medium supplemented with either the full set of amino acids or the full set of vitamins (or sugars, though we won't examine that case here).
If a mutant grew on minimal medium with amino acids (but not vitamins), it must be unable to make one or more amino acids.
If a mutant grew on the vitamin medium but not the amino acid medium, it must be unable to make one or more vitamins.
If a mutant grew on minimal medium containing all 20
amino acids, they might next test it in 20different vials, each containing minimal medium plus just one of the 20 amino acids. If the mutant grew in one of these vials, Beadle and Tatum knew that the amino acid in that vial must be the end product of the pathway disrupted in the mutant |
| mutation | to any heritable change in a gene (or, more generally, in the genetic material) or to the process by which such a change takes place. |
| One type of mutation results | in a change in the sequence of bases in DNA. |
| how can the change in mutation be simple | such as the substitution
of one pair of bases in a duplex molecule for a
different pair of bases |
| how can the change in nucleotide sequence may
also be more complex | such as the deletion or addition of base pairs |
| different mutations can give rise to phenylketonuria which results in change of | one/single base pair |
| One gene can affect more than one trait | Pleiotropy
PKU = fair skin/blonde hair low concentration of pigment |
| phenylalanine is degraded into | tyrosine (if enzymes are functional) = precursor for the synthesis of melanin pigment, pleiotropy occurred the children with PKU are not capable of producing tyrosine is not been broken down. |
| Any trait can be affected by more than one gene | polygenic or multigenic inheritance
ex: Same Phenylalanine levels in blood but different PKU severity levels, genes regulated blood barrier can be functioning different ways. blood-brain barrier is necessary to limit the movement of water soluble molecules from the blood into the brain. Limiting the movement the phenylalanine into the brain so less severe consequences will be in neural development will be better. |
| Most traits are affected by environmental factors
as well as genes | PKU can be made less severe in case of Phe-low diet |
