DNA: The molecular basis of mutationsSince mutations are simply changes in DNA, in order to understand how mutations work,...
Protein-coding DNA can be divided into codons — sets of threebases that specify an amino acid or signal the end of the pro...
Frameshift                          Since protein-coding DNA is divided into codons three bases long,                     ...
Since all cells in our body contain DNA, there are lots of places formutations to occur; however, some mutations cannot be...
Many organisms have powerful control genes that determine how the body is laid out. Forexample, Hox genes are found in man...
A case study of the effects of mutation: Sickle cell anemiaSickle cell anemia is a genetic disease with severe symptoms, i...
Normal hemoglobin (left) and hemoglobin in sickled red blood cells (right) look        different; the mutation in the DNA ...
the organism resistant to those chemicals. In this respect, mutations are random — whether aparticular mutation happens or...
of antibiotic resistance. Esther and Joshua Lederberg determined that many of these mutationsfor antibiotic resistance exi...
So the penicillin-resistant bacteria were there in the population before they encounteredpenicillin. They did not evolve r...
Upcoming SlideShare
Loading in …5
×

Molecular basis and mutation by umerfarooq

1,507 views
1,412 views

Published on

Published in: Technology
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,507
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
31
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Molecular basis and mutation by umerfarooq

  1. 1. DNA: The molecular basis of mutationsSince mutations are simply changes in DNA, in order to understand how mutations work, youneed to understand how DNA does its job. Your DNA contains a set of instructions for"building" a human. These instructions are inscribed in the structure of the DNA moleculethrough a genetic code. It works like this: DNA is made of a long sequence of smaller units strung together. There are four basic types of unit: A, T, G, and C. These letters represents the type of base each unit carries: adenine, thymine, guanine, and cytosine. The sequence of these bases encodes instructions. Some parts of your DNA are control centers for turning genes on and off, some parts have no function, and some parts have a function that we dont understand yet. Other parts of your DNA are genes that carry the instructions for making proteins — which are long chains of amino acids. These proteins help build an organism. 1
  2. 2. Protein-coding DNA can be divided into codons — sets of threebases that specify an amino acid or signal the end of the protein.Codons are identified by the bases that make them up — in theexample at right, GCA, for guanine, cytosine, and adenine. Thecellular machinery uses these instructions to assemble a string ofcorresponding amino acids (one amino acid for each three bases)that form a protein. The amino acid that corresponds to "GCA" iscalled alanine; there are twenty different amino acids synthesizedthis way in humans. "Stop" codons signify the end of the newlybuilt protein.After the protein is built based on the sequence of bases in the gene, the completed protein isreleased to do its job in the cell.Types of mutationsThere are many different ways that DNA can be changed, resulting in different types ofmutation. Here is a quick summary of a few of these: Substitution A substitution is a mutation that exchanges one base for another (i.e., a change in a single "chemical letter" such as switching an A to a G). Such a substitution could: 1. change a codon to one that encodes a different amino acid and cause a small change in the protein produced. For example, sickle cell anemia is caused by a substitution in the beta-hemoglobin gene, which alters a single amino acid in the protein produced. 2. change a codon to one that encodes the same amino acid and causes no change in the protein produced. These are called silent mutations. 3. change an amino-acid-coding codon to a single "stop" codon and cause an incomplete protein. This can have serious effects since the incomplete protein probably wont function. Insertion Insertions are mutations in which extra base pairs are inserted into a new place in the DNA. Deletion Deletions are mutations in which a section of DNA is lost, or deleted. 2
  3. 3. Frameshift Since protein-coding DNA is divided into codons three bases long, insertions and deletions can alter a gene so that its message is no longer correctly parsed. These changes are called frameshifts. For example, consider the sentence, "The fat cat sat." Each word represents a codon. If we delete the first letter and parse the sentence in the same way, it doesnt make sense. In frameshifts, a similar error occurs at the DNA level, causing the codons to be parsed incorrectly. This usually generates truncated proteins that are as useless as "hef atc ats at" is uninformative. There are other types of mutations as well, but this short list should give you an idea of the possibilities.The causes of mutationsMutations happen for several reasons.1. DNA fails to copy accuratelyMost of the mutations that we think matter to evolution are "naturally-occurring." For example,when a cell divides, it makes a copy of its DNA — and sometimes the copy is not quite perfect.That small difference from the original DNA sequence is a mutation.2. External influences can create mutationsMutations can also be caused by exposure to specific chemicals orradiation. These agents cause the DNA to break down. This is notnecessarily unnatural — even in the most isolated and pristineenvironments, DNA breaks down. Nevertheless, when the cell repairsthe DNA, it might not do a perfect job of the repair. So the cell wouldend up with DNA slightly different than the original DNA and hence,a mutation.The effects of mutations 3
  4. 4. Since all cells in our body contain DNA, there are lots of places formutations to occur; however, some mutations cannot be passed on tooffspring and do not matter for evolution. Somatic mutations occur in non-reproductive cells and wont be passed onto offspring. For example, thegolden color on half of this Red Delicious apple was caused by a somaticmutation. Its seeds will not carry the mutation.The only mutations that matter to large-scale evolution are those that can be passed on tooffspring. These occur in reproductive cells like eggs and sperm and are called germ linemutations.Effects of germ line mutationsA single germ line mutation can have a range of effects: 1. No change occurs in phenotype. Some mutations dont have any noticeable effect on the phenotype of an organism. This can happen in many situations: perhaps the mutation occurs in a stretch of DNA with no function, or perhaps the mutation occurs in a protein-coding region, but ends up not affecting the amino acid sequence of the protein. 2. Small change occurs in phenotype. A single mutation caused this cats ears to curl backwards slightly. 3. Big change occurs in phenotype. Some really important phenotypic changes, like DDT resistance in insects are sometimes caused by single mutations. A single mutation can also have strong negative effects for the organism. Mutations that cause the death of an organism are called lethals — and it doesnt get more negative than that.Little mutations with big effects: Mutations to control genesMutations are often the victims of bad press — unfairly stereotyped as unimportant or as a causeof genetic disease. While many mutations do indeed have small or negative effects, another sortof mutation gets less airtime. Mutations to control genes can have major (and sometimespositive) effects.Some regions of DNA control other genes, determining when and where other genes are turned"on". Mutations in these parts of the genome can substantially change the way the organism isbuilt. The difference between a mutation to a control gene and a mutation to a less powerful geneis a bit like the difference between whispering an instruction to the trumpet player in an orchestraversus whispering it to the orchestras conductor. The impact of changing the conductorsbehavior is much bigger and more coordinated than changing the behavior of an individualorchestra member. Similarly, a mutation in a gene "conductor" can cause a cascade of effects inthe behavior of genes under its control. 4
  5. 5. Many organisms have powerful control genes that determine how the body is laid out. Forexample, Hox genes are found in many animals (including flies and humans) and designatewhere the head goes and which regions of the body grow appendages. Such master control geneshelp direct the building of body "units," such as segments, limbs, and eyes. So evolving a majorchange in basic body layout may not be so unlikely; it may simply require a change in a Hoxgene and the favor of natural selection. Mutations to control genes can transform one body part into another. Scientists have studied flies carrying Hox mutations that sprout legs on their foreheads instead of antennae! 5
  6. 6. A case study of the effects of mutation: Sickle cell anemiaSickle cell anemia is a genetic disease with severe symptoms, including pain and anemia. Thedisease is caused by a mutated version of the gene that helps make hemoglobin — a protein thatcarries oxygen in red blood cells. People with two copies of the sickle cell gene have the disease.People who carry only one copy of the sickle cell gene do not have the disease, but may pass thegene on to their children.The mutations that cause sickle cell anemia have been extensively studied and demonstrate howthe effects of mutations can be traced from the DNA level up to the level of the whole organism.Consider someone carrying only one copy of the gene. She does not have the disease, but thegene that she carries still affects her, her cells, and her proteins: 1. There are effects at the DNA level 2. There are effects at the protein level 6
  7. 7. Normal hemoglobin (left) and hemoglobin in sickled red blood cells (right) look different; the mutation in the DNA slightly changes the shape of the hemoglobin molecule, allowing it to clump together. 3. 4. There are effects at the cellular level When red blood cells carrying mutant hemoglobin are deprived of oxygen, they become "sickle-shaped" instead of the usual round shape (see picture). This shape can sometimes interrupt blood flow. 5. There are negative effects at the whole organism level Under conditions such as high elevation and intense exercise, a carrier of the sickle cell allele may occasionally show symptoms such as pain and fatigue. 6. There are positive effects at the whole organism level Carriers of the sickle cell allele are resistant to malaria, because the parasites that cause this disease are killed inside sickle-shaped blood cells. Normal red blood cells (top) andThis is a chain of causation. What happens at the DNA level sickle cellspropagates up to the level of the complete organism. This example (bottom)illustrates how a single mutation can have a large effect, in thiscase, both a positive and a negative one. But in many cases, evolutionary change is based on theaccumulation of many mutations, each having a small effect. Whether the mutations are large orsmall, however, the same chain of causation applies: changes at the DNA level propagate up tothe phenotype.Mutations are randomMutations can be beneficial, neutral, or harmful for the organism, but mutations do not "try" tosupply what the organism "needs." Factors in the environment may influence the rate of mutationbut are not generally thought to influence the direction of mutation. For example, exposure toharmful chemicals may increase the mutation rate, but will not cause more mutations that make 7
  8. 8. the organism resistant to those chemicals. In this respect, mutations are random — whether aparticular mutation happens or not is unrelated to how useful that mutation would be.For example, in the U.S. where people have access to shampoos with chemicals that kill lice, wehave a lot of lice that are resistant to those chemicals. There are two possible explanations forthis: Hypothesis A: Hypothesis B: Resistant strains of lice were Exposure to lice shampoo always there — and are just actually caused mutations for more frequent now because all resistance to the shampoo. the non-resistant lice died a sudsy death.Scientists generally think that the first explanation is the right one and that directed mutations,the second possible explanation relying on non-random mutation, is not correct.Researchers have performed many experiments in this area. Though results can be interpreted inseveral ways, none unambiguously support directed mutation. Nevertheless, scientists are stilldoing research that provides evidence relevant to this issue.In addition, experiments have made it clear that many mutations are in fact random, and did notoccur because the organism was placed in a situation where the mutation would be useful. Forexample, if you expose bacteria to an antibiotic, you will likely observe an increased prevalence 8
  9. 9. of antibiotic resistance. Esther and Joshua Lederberg determined that many of these mutationsfor antibiotic resistance existed in the population even before the population was exposed to theantibiotic — and that exposure to the antibiotic did not cause those new resistant mutants toappear.The Lederberg experimentIn 1952, Esther and Joshua Lederberg performed an experiment that helped show that manymutations are random, not directed. In this experiment, they capitalized on the ease with whichbacteria can be grown and maintained. Bacteria grow into isolated colonies on plates. Thesecolonies can be reproduced from an original plate to new plates by "stamping" the original platewith a cloth and then stamping empty plates with the same cloth. Bacteria from each colony arepicked up on the cloth and then deposited on the new plates by the cloth.Esther and Joshua hypothesized that antibiotic resistant strains of bacteria surviving anapplication of antibiotics had the resistance before their exposure to the antibiotics, not as a resultof the exposure. Their experimental set-up is summarized below: 1. Bacteria are spread out on a plate, called the "original plate." 2. They are allowed to grow into several different colonies. 3. This layout of colonies is stamped from the original plate onto a new plate that contains the antibiotic penicillin. 4. Colonies X and Y on the stamped plate survive. They must carry a mutation for penicillin resistance. 5. The Lederbergs set out to answer the question, "did the colonies on the new plate evolve antibiotic resistance because they were exposed to penicillin?" The answer is no: When the original plate is washed with penicillin, the same colonies (those in position X and Y) live — even though these colonies on the original plate have never encountered penicillin before. 9
  10. 10. So the penicillin-resistant bacteria were there in the population before they encounteredpenicillin. They did not evolve resistance in response to exposure to the antibiotic. By Umerfarooq Dogar b.s botany university of gujrat 10

×