CENTRAL DOGMA, GENES & MUTATIONS

Central Dogma After the discovery of DNA’s structure, scientists turned to investigating how DNA served as a genetic code for the synthesis of proteins. Geneticists accept that the basic mechanism for reading and expressing genes is from DNA to RNA to protein. This is referred to as the central dogma of biology: DNA codes for RNA, which guides the synthesis of proteins.

RNA RNA is a nucleic acid similar to DNA, but with the sugar ribose, and with uracil instead of thymine. Messenger RNA (mRNA): long strands of RNA that are formed complementary to one strand of DNA; direct synthesis of a specific protein Ribosomal RNA (rRNA): associates with proteins to form ribosomes in the cytoplasm Transfer RNA (tRNA): smaller segments of RNA that transport amino acids to the ribosome

Transcription First step of the central dogma involves the synthesis of mRNA from DNA in a process called transcription. The enzyme RNA polymerase regulates RNA synthesis by binding to the specific section where an mRNA will be synthesized. RNA polymerase moves along the DNA strand in a 3’ to 5’ direction, synthesizing mRNA.

RNA Processing In comparing DNA code with its transcribed mRNA code, scientists found that the mRNA code was much shorter. DNA sequences not found in mRNA are called introns. DNA sequences that remain in the final mRNA are called exons.

The Code Scientists hypothesized that the instructions from protein synthesis were encoded in DNA. Experiments during the 1960s demonstrated that the DNA code was a three-base code. The three-base code in DNA or mRNA is called a codon.

Translation After synthesis, mRNA moves from the nucleus into the cytoplasm, where it connects at the 5’ end to a ribosome. The mRNA code is read and translated into a protein through a process called translation.

Translation tRNA molecules act as the interpreters of the mRNA codon sequence. The tRNA is activated by an enzyme that attaches a specific amino acid to the 3’ end. The middle of the folded tRNA contains an anticodon, a complementary sequence to the mRNA codon.

The Role of the Ribosome Ribosomes provide a site for protein synthesis. When mRNA leaves the nucleus, the two ribosomal subunits come together to hold the mRNA in place for translation. The ribosome structure has grooves that hold serve as tRNA sites for amino acid attachment.

One Gene—One Enzyme The Beadle and Tatum experiment showed that one gene codes for one enzyme. We now know that one gene codes for one polypeptide.

Prokaryote Gene Regulation Gene regulation is the ability of an organism to control which genes are transcribed in response to the environment. An operon is a section of DNA that contains the genes for the proteins needed for a specific metabolic pathway. An operon contains: Operator – on/off switch Promoter – where RNA polymerase binds Regulatory gene Genes coding for proteins

Prokaryote Gene Regulation The lac operon When lactose is present, E. coli can synthesize an enzyme to use it as an energy source. The lac operon is an inducible operon because an inducer binds to the repressor and inactivates it, allowing transcription to be turned on.

Prokaryote Gene Regulation The trp operon Tryptophan synthesis occurs in five steps controlled by the trp operon. The trp operon is a repressible operon, because it is usually repressed or turned off.

Eukaryote Gene Regulation - Controlling transcription Transcription factors ensure that a gene is used at the right time and that proteins are made in the right amounts. Complexes that guide the binding of the RNA polymerase to a promoter Regulatory proteins that help control the rate of transcription The complex structure of eukaryotic DNA also regulates transcription.

Eukaryote Gene Regulation Hox genes Gene regulation is crucial during development and cell differentiation. One group of genes that control cell differentiation is the homeobox (Hox) gene group. Hox genes are transcribed at specific times in specific places on the genome, and control what body part will develop at a giving body location.

Eukaryote Gene Regulation RNA interference RNA interference (RNAi) can stop the mRNA from translating its message. Single-stranded small interfering RNA and protein complexes bind to mRNA and stop translation.

A mutation is a change in the DNA or RNA sequence Many mutations result in new alleles. Some of these changes have been beneficial. Evolution could not take place without the genetic variation that results from mutations. Most mutations are harmful Also, chromosomal mutations, large changes with dramatic effects

Causes of mutation Can occur spontaneously – DNA polymerase can attach the wrong nucleotide, but this is rare and usually corrected. Certain chemicals and radiation called mutagens can damage DNA. Chemicals can cause mispairing of base pairs, or themselves substitute for base pairs. High-energy radiation can eject electrons from atoms within the DNA molecule, leaving behind unstable free radicals.

Types of mutations A permanent change that occurs in a cell’s DNA is called a mutation. Point mutation: involve chemical change to just one base pair Missense substitutions: DNA codes for the wrong amino acid Nonsense mutation: Codon for amino acid becomes a stop codon Insertion/deletion: additions/ loss of a nucleotide to the DNA sequence Cause “frameshifts”

TYPES OF MUTATIONS Various types of mutations can all have severe effects on the individual. These include: point mutations frameshift mutations chromosomal alterations Mutations that disrupt the reading frame by insertions or deletions of a non-multiple of 3 nucleotide bases are known as frameshift mutations.

MR BLAKE IS A GOOD TEACHER A deletion mutation that disrupts the reading frame, results in a message that does not make any sense or adds a different meaning.

MR BLAKE IS A GOD TEACHER Now Mr. Blake is a teacher of Gods. Who did teach Zeus? Was Mr. Blake Thor's tutor when he was a child? An insertion mutation that disrupts the reading frame, results in a message that does not make any sense or adds a different meaning.

MRS BLAKE IS A GOOD TEACHER Now the gender of the teacher is changed which gives you a new picture of who your teacher is. If the reading frame is disrupted, as in these frameshift mutations, the RNA may not be translated properly. These mutations may impair the function of the resulting protein, if the protein is even formed. Many frameshift mutations result in a premature stop codon, in other words, a stop codon that comes earlier than normal during translation. This would result in a smaller protein, most likely without normal function. Point mutations are different because they do not change the three letter reading frame of the codon. Instead, a single letter base is replaced with a different letter.

MR BLAKE IS A GOON TEACHER This kind of point mutation will generally change only one amino acid in the protein, or might not change the amino acid sequence at all. Sometimes these mutations are not harmful, but sometimes they can be devastating. Tay-Sachs disease is an example of a fatal disease that occurs because of a single letter change in the DNA code.

Protein folding and stability Even small changes in the DNA code can cause genetic disorders. The change in one amino acid can change the sequence of the protein enough to affect both the folding and stability of the protein.

Body-cell v. sex-cell mutation Somatic cell mutations are not passed on to the next generation. Mutations that occur in sex cells are passed on to the organism’s offspring and will be present in every cell of the offspring.

MOST MUTATIONS HAVE NO BENEFIT OR HARM TO THE ORGANISM. A cell that has a mutation may die off on it’s own before it can reproduce, or the mutation may not effect the function of the cell so the mutation is never noticed. Some mutations have been beneficial while others are harmful.

REVIEW QUESTIONS 1.How are messenger RNA, ribosomal RNA, and transfer RNA involved in the transcription and translation of genes? 2.What is the role of RNA polymerase in the synthesis of messenger RNA? 3.How is the code of DNA translated into messenger RNA and utilized to synthesize a protein ? 4.How are bacteria able to regulate their genes by two types of operons? 5.How do eukaryotes regulate the transcription of genes? 6.What are the various types of mutations?