BIOL 130 Chapter 6 DNA, Protein Synthesis, and Mutations

DNA

• NEEDS AN IMAGE SLIDE 3

• otherwise known as deoxyribonucleic acid

• shown are the four nucleic acids that bind to each other as shown, A-T and G-C as, ‘complementary base pairs’, while the sugar-phosphate backbone structures bind to form a chain.

DNA chain

• NEEDS IMAGE SLIDE 4

• often referred to as a double helix.

• the left side structure of RNA is shown is a single helix, the DNA on the right is a double helix.

• the pattern of A-T and G-C down the chain encodes for genes.

DNA replication

• NEEDS IMAGE SLIDE 6

• the process in which DNA is copied

• DNA must be copied so that, after cell division occurs, each daughter cell will have a complete set of chromosomes.

Steps of DNA replication

• NEED IMAGE SLIDE 7

1. an enzyme breaks the bonds between complementary bases in the molecule

2. expose the bases inside the molecule so they can “read” by another enzyme

3. build two new DNA strands with complementary bases

the two daughter molecules that result each contain one strand from the new parent molecule and one new strand that is complementary to it. as a result, the two daughter molecules are both identical to the parent molecule. this is a semi-conservation process in that each new strand is half new, half old.

RNA

• otherwise known as ribose nucleic acid

• RNA structure differs from the DNA structure in three specific ways

1. both are nucleic acids and made of nucleotides; BUT RNA is single stranded

2. RNA nucleotides contain the 5-carbon sugar ribose, whereas in DNA, the sugar is deoxyribose

3. RNA contains the nitrogenous base uracil instead of thymine. Uracil pairs with adenine in RNA, A-U not A-T since RNA does not have thymine

length of RNA v DNA

• NEED IMAGE FROM SLIDE 9

• the nucleotide sequence of RNA, which is complementary to the DNA sequence, allows RNA to encode genetic information. RNA though carries the genetic information of just one gene. Hence, compared to DNA, RNA molecules are relatively small. A full DNA strand can be 2 meters long. RNA strands are about 300 nm long. A nanometer is one billionth of a meter.

Human chromosomes

• NEED IMAGE FROM SLIDE 11

• Human cells normally have two sets of chromosomes in each of their cells, one set inherited from each parent. There are 23 chromosomes in each set, for a total of 46 chromosomes per cell

• each chromosome in one set is matched by a chromosome of the same type in the other set, so there are actually 23 pairs of chromosomes per cell

allele

• each similar gene is called a (blank), one allele from each parent.

• each pair consists of chromosomes of the same size and shape, and they also contain the same genes.

chromosomes and genes

• NEED IMAGE SLIDE 13

• this linkage map shows the locations of several genes on one half of a full X chromosome

• each gene shown is one of a pair of alleles, the other allele half of the X

Chromosome to DNA

• NEED IMAGE FROM SLIDE 13

• graphic decomposition of a chromosome (found in the cell nucleus), to the bases pair of the DNA. chromosomes are located in the nucleus of the cell. a duplicated chromosome has two chromatids, double-helix DNA is wrapped in histone

misconception about chromosomes

chromatin, DNA strands not bundled into a chromosome, is the most common version of DNA. DNA condenses into chromosomes only just prior to cell division. chromosomes are too compact to allow for gene expression. yet most versions of DNA shown in texts are as chromosomes.

transcription

• takes place in three steps: called initiation, elongation, and termination

1. initiation

step one and the beginning of transcription. it occurs when the enzyme RNA polymerase binds to a region of a gene called the promoter. this signals the DNA to unwind so the enzyme can “read” the bases in one of the DNA strands. the enzyme is ready to make a strand of mRNA with a complementary sequence of bases. the promoter is not part of the resulting mRNA.

IMAGE FROM SLIDE 16

2. elongation

step two the addition of nucleotides to the mRNA strand.

IMAGE FROM SLIDE 16

3. termination

step three, the ending of transcription. as RNA polymerase transcribes the terminator, it detaches from DNA.

IMAGE FROM SLIDE 16

processing

NEED IMAGE FROM SLIDE 17

• in eukaryotes, the new mRNA is not yet ready for translation. at this stage, it is called pre-mRNA and it must go through more processing before it leaves the nucleus as mature mRNA

• splicing removes introns from the protein-coding sequence of mRNA.the remaining mRNA consists only of regions called exons that do code for the protein.

introns

regions that do not code for protein.

translation

• the process in which the genetic code in mRNA is read to make a protein

• this process happens on the ribosomes floating in the cytosol, or on the ribosomes attached to the rough endoplasmic reticulum

• the ribosome reads the sequence of codons in mRNA and molecules of tRNA bring amino acids to the ribosome in the correct sequence

protein synthesis

• can be divided into three phases

1. initiation

2. elongation

3. termination

translation initiation

the small ribosomal subunit binds to a site upstream (on the 5’ side) of the start of the mRNA. it proceeds to scan the mRNA in the 5’ → 3’ direction until it encounters the START codon (aug)

IMAGE SLIDE 21

translation initiation

that large subunit attaches and the initiator tRNA, which carries methionine (Met), binds to the P site on the ribosome

• A site: aminoacyl

• P site: peptidyl

• E site: exit

IMAAGE ON SLIDE 22

translation elongation

• the ribosome shifts one codon at a time, catalyzing each process that occurs in the three sites. with each step, a charged tRNA enters the complex, the polypeptide becomes on amino acid longer, and an uncharged tRNA departs. briefly, the ribosomes interact with other RNA molecules to make chains of amino acids called polypeptide chains.

• inside the ribosome, three sites participate in the translation process, the A, P, and E sites

• amazing, the E. coli translation apparatus takes only 0.05 seconds to add each amino acid, meaning that a 200-amino acid polypeptide could be translated in just 10 seconds.

IMAGE ON SLIDE 23

translation termination

• occurs when a stop codon (UAA, UAG, or UGA) is encountered

• when the ribosome encounters the stop codon, the growing polypeptide is released with the help of various releasing factors and the ribosome subunits dissociate and leave the mRNA

• after many ribosomes have completed translation, the mRNA is degraded so the nucleotides can be reused in another transcription reaction

summary of DNA to protein

• instructions on DNA are transcribed onto messenger RNA. ribosomes are able to read the genetic information inscribed on a strand of messenger RNA and use this information to string amino acids together into a protein
  IMAGE ON SLIDE 27 28

DNA and mRNA

• DNA is transcribed to pre-mRNA

• processing forms mRNA

• mRNA is translated by free ribosomes in the cytoplasm and creates a protein that is used inside the cell

• mRNA is translated to a protein by rough ER ribosomes entering the endomembrane system and is then exocytosed to be used outside the cell
  IMAGE ON 29

mutations

• also known as mutagenesis, is a processing by which the genetic information of an organism is changed in a stable manner, resulting in blank

• in nature, mutagenesis can lead to changes that are beneficial or harmful or have no effect. harmful mutation can lead to cancer and various heritable diseases

• beneficial mutations are the driving force of evolution

• in 1927, hermann muller first demonstrated the effects of mutations with observable changes in chromosomes. he induced mutagenesis by irradiating fruit flies with x-rays

what mutations look like in DNA

IMAGE ON SLIDE 33

• in one common damage event, adjacent bases bond with each other, instead of across the “ladder”. this makes a bulge, and the distorted DNA molecule does not function properly

mutations with chromosomes

IMAGE SLIDE 34

• chromosomal alterations may occur due to deletion or duplication of genes in a chromosome, inversion of a section of a chromosome, insertion of genes from one chromosome to another, or exchanges of genes between two chromosomes

coding sequence (mutation)

IMAGE SLIDE 35

• The frame of the coding sequence of a gene changes when a nucleotide gets

  deleted due to mutation. Normal gene codes for a polypeptide met-lys-phe-gly-

  ile-val-pro. When a U from the third position of the third codon gets deleted, the

  polypeptide reduced to met-lys- leu-ala because the third and fourth codons

  code for different amino acids and the fifth codon converts to a stop codon.

effects of mutations

• the majority of mutations have neither negative nor positive effects on the organism in which they occur. these mutations care called neutral mutations. examples include silent point mutations, which are neutral because they do not change the amino acids in the proteins they encode.

• many other DNA damages or errors have no effect on the organism because they are repaired before protein synthesis occurs. cells have multiple repair mechanisms to fix errors in DNA.

beneficial mutations

• some mutations have a positive effect on the organism in which they occur. they generally code for new versions of proteins that help organisms adapt to their environment. if they increase an organism’s chances of surviving or reproducing, the mutations are likely to become more common over time.

• examples:

1. mutations have occurred in bacteria that allow the bacteria to survive in the presence of antibiotic drugs. the mutations have lead to the evolution of antibiotic resistant strains of bacteria

2. a unique mutation is found in people in a small town in Italy. the mutation protects them from developing atherosclerosis, which is the dangerous buildup of fatty materials in blood vessels. the individual in which the mutation first appeared has even been identified.

giovanni pomarelli

Was born in the village of Limone sul Garda in 1780 with a single

replacement of arginine by cysteine at position 173 (197 for UniProt).

The mutation is known in single nucleotide polymorphism (SNP)

nomenclature as rs28931573. He passed this on to his offspring.

The ApoA-I Milano mutation was found by University of

Milan researchers after their 1974 investigation of a

low HDL / high triglyceride phenotype exhibited by Valerio Dagnoli

of Limone sul Garda, a small village in northern Italy. Limone had only

1,000 inhabitants at the time and when blood tests were run on the

entire population of the village, the mutation was found to be

present in about 3.5% of the local population

harmful mutations

• imagine making a random change in a complicated machine such as a car engine. the chance that the random change would improve the functioning of the car is very small. the change is far more likely to result in a car that does not run well or perhaps does not run at all. by the same token, any random change in a gene’s DNA is likely to result in the production of a protein that does not function normally or may not function at all.

• such mutations are likely to be harmful. these mutations may cause genetic disorders or cancer.

genetic disorder

• a disease, syndrome, or other abnormal condition caused by a mutation in one or more genes or by a chromosomal alteration.

• an example is cystic fibrosis. a mutation in a single gene causes the body to produce thick, sticky mucus that clods the lungs and blocks ducts in digestive organs.

• cancer is a disease in which cells grow out of control and form abnormal masses of cells called tumors. it is generally caused by mutations in genes that regulate the cell cycle. because of the mutations, cells with damaged DNA are allowed to divide without restrictions.