Chromosomal Mutations. 2. Gene Mutations

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1 Chromosomal 3. NOT! 2. Gene A genetic mutation is any change in the DNA nucleotide sequence. Mutation is caused by mistakes during DNA replication, as well as mutagens, like certain chemicals and radiation. Number 3 represents the fictional misconception that a mutagen can transform an individual into a monster or superhero. Gene mutations occur during DNA replication before cell division, and from damage caused by mutagens. Chromosomal mutations happen both during replication and cell division due to damage and improper sorting. Gene mutations usually affect one gene at a time. Chromosomal mutations 31 can affect 100s to 1000s of genes at a time and are usually lethal.

2 Gene A point mutation is a change in just one DNA nucleotide, or base pair. 1) Substitution 2) Insertion 3) Deletion The substitution shown is a change from DNA nucleotide C to nucleotide T. This produces a change from RNA nucleotide G to nucleotide A. This produces a change from the amino acid Arginine to the amino acid Histadine in the polypeptide. This may or may not effect the final conformation or function of the polypeptide/protein. The potential severity of this mutation type ranges from neutral to lethal if it eliminates the function of an enzyme or other protein crucial to survival. Transcription Translation Transcription Translation 32

3 Gene of The insertion shown inserts the DNA nucleotide T between the and A and C nucleotides. This causes the mrna nucleotide A to be inserted between the U and G nucleotides. This produces a frame shift in the way the mrna codons are read during translation, so that every codon downstream from the point of insertion is read incorrectly. This results in most amino acids in the resulting polypeptide being different, which completely changes the structure and function of the polypeptide/protein. Frame shift resulting from either insertions or deletions are potentially the most severe, most often completely eliminating the structure and function of the resulting polypeptide/protein. Transcription Translation Transcription Translation 33

4 Gene of This analogy equates the 3 nucleotide codons of mrna with a sentence of only 3 letter words. The letter H in the first word is deleted. This produces a frame shift so that every 3 letters (nucleotides) is no longer a word (correct codon). Just as the sentence no longer makes sense, neither would the mrna nucleotide sequence. A protein resulting from this deletion and frame shift would have a completely different structure and eliminated function. A missense mutation produces a polypeptide with the wrong amino acids. A nonsense mutation produces a premature stop codon so the polypeptide is incomplete. 34

5 Chromosomal Of Structure A chromosomal mutation is any change in DNA resulting from a change in chromosome 1) structure or 2) number. This diagram represents chromosomal mutations of structure. Chromosomal deletion is when a section of chromosome is lost. Chromosomal duplication is when there is Many genes lost! an extra copy of a chromosome section. Chromosomal inversion is when a section of chromosome flips, causing the sequence to be reversed. Chromosomal translocation is when a May give rise to new genes! section of chromosome moves from one chromosome to another. Reciprocal translocation is when two chromosomes trade sections. Genes broken & separated! Chromosomal mutations are often fatal, since they affect many genes at once. The most severe is deletion, because genes are lost. Extra genes resulting from duplication can cause the overproduction of proteins. Inversion and translocation can break, separate and reorder genes. 35

6 Chromosomal Of Number This slide represents chromosomal mutations of number (aneuploidy). Polyploidy is having more than 2 homologous sets of chromosomes. Strawberry species and hybrids can have 2, 4, 5, 6, 7, 8, or 10 sets of the seven strawberry chromosomes. A karyotype is an ordered arrangement of chromosomes from one mitotic cell of an individual obtained from chorionic villi, amniotic fluid, blood or bone marrow. The chromosomes are spilled out, photographed, and arranged according to size and banding pattern. Karyotyping can diagnose disorders like Down syndrome and cri du chat syndrome. A neutral mutation is one that has no phenotypic effect. Mutation is beneficial as it increases variation allowing for natural selection and evolution. 36

7 12-5 Gene Regulation: A Prokaryotic Example RNA Polymerase An operon is a set of linked prokaryotic genes plus their regulatory elements. The operon in this diagram is the Lac operon found in E. coli. The genes in this operon code for the enzymes that break down lactose so that E. coli can use it as a source of energy (eat it). The two regulatory regions are the Promoter and the Operator. The promoter region is a sequence of DNA where RNA Polymerase can bind. The operator region is a sequence of DNA where the Repressor can bind. The repressor is a protein that, when bound to the Operator, stops transcription. This operon is off because the Repressor is bound to the Operator, blocking RNA Polymerase from transcribing the Lac genes. The consequence of this operon state for E. coli is that it can not digest lactose. 37

8 Gene Regulation: A Prokaryotic Example Lactose Promoter Repressor Operator Lac Genes RNA Polymerase In this diagram, Lactose has bound the Repressor, which has released the Operator, allowing for RNA Polymerase to transcribe the Lac genes. The process synthesizing RNA is transcription. Three different mrnas will be created, one from each Lac gene. The process mrna will participate in is translation or protein synthesis which will result in three Lac enzymes. The consequence of this operon state is that E. coli will be able to digest lactose. Some prokaryotic genes are regulated individually. Gene expression may also be regulated during protein translation. 38

9 Gene Regulation Upstream enhancer A Eukaryotic Generalization TATA box Promoter sequences Introns Exons Direction of transcription Eukaryotic gene expression is more complex and finely regulated because the eukaryotic cell and being multicellular is more complex. This diagram is different because it represents the regulation of only one gene with introns and exons, shows multiple Promoter sequences, includes a TATA box and an upstream enhancer sequence not found in prokaryotes. The eukaryotic promoter sequences allow for the binding of RNA polymerase, along with other transcription factors. The TATA box is a sequence containing TATAAA repeats that identifies the start of a gene sequence and functions along with the Promoter sequences. The upstream enhancer region is a sequence far from the gene it regulates to which both enhancer and inhibitory transcription factors may bind. Upstream refers to the location opposite the direction or flow of transcription. Transcription factors are regulatory proteins specialized to bind specific regulatory sequences and enhance, inhibit, or modulate transcription. Eukaryotic genes can be regulated at transcription, RNA processing, nuclear exit, RNA interference and degradation, protein translation, protein processing, enhancement, 39 inhibition, and degradation.

10 Gene Regulation Development and Differentiation Review: As multicellular organisms develop, changes in gene expression causes cells to differentiate and become specialized to perform specific functions within specialized tissues, organs, and organ systems. Homeobox (HOX) genes are master Fruit fly chromosomemouse chromosomes control genes found in all animals that orchestrate the expression of the other genes associated with the development of whole body regions or structures. Mutation or changes in HOX gene regulation can have profound effects on the development Fruit fly embryo and evolution of the animal body. Mouse embryo The colored bars in the chromosomes represent individual HOX genes that correspond to and regulate the development of the same colored animal body regions. Mice (vertebrate mammal) have more chromosomes and HOX genes than fruit flies (invertebrate arthropod), which Adult mouse corresponds to comparative complexity Adult fruit fly of these animals. This suggests that the increase in complexity represented by the evolution of the vertebral column involved the duplication and mutation of HOX genes. 40