L14 - Mutation, genetic variation, evolution Flashcards
What is genetic mutation?
Mutations are inherited alterations in the genetic material. Two humans differ (on average) at 1/1000 bp - mutations are the source of this variation. Most are neutral, many are harmful, some are beneficial. Mutations don’t happen due to an organism trying to create it. Source of all genetic variation, provide raw material for evolution. Studying mutations can be useful for probing fundamental biological processes.
Somatic vs germ line mutations?
Somatic mutations occur in nonreproductive cells and are passed to new cells through mitosis, creating a clone of cells having the mutant gene. Germ line mutations occur in cells that give rise to gametes, meiosis and sexual reproduction allow germ-line mutations to be passed to approximately half the members of the next generation who will carry the mutation in all their cells.
With what frequency do somatic mutations happen?
Frequently due to the high number of cell divisions occuring. Most have few consequences as the cell dies or its function is taken over by surrounding cells. Mutations can lead to conditions such as cancer.
What is a somatic mutation and ex?
A somatic mutation in the Japanese morning glory results in sectors of pigmentation. A mutation occurred in the flower-colour gene in one cell and is passed on to its descendents. The mutation effects the ability to make purple/pink pigment.
Somatic mutation and cancer?
Most cancers results from mutations in somatic cells. A mutation that increases the risk of disease in an individual is called a genetic risk factor for that disease. Each mutation occurs randomly, but if a mutation in the Ras gene occurs in a cell that is derived from one in which the APC gene has been mutated, that cell’s progeny will form a polyp. Another chance mutation in the cell line having mutations in both the APC and Ras genes could lead to malignant cancer.
What are the types of gene mutation?
Substitution, insertion, and deletion.
What are base substitution?
A base substitution alters a single codon.
What are base insertion & deletion?
An insertion or a deletion alters the reading frame and may change many codons.
Information about types of gene mutation?
Insertions and deletions seem to occur more frequently than base substitutions. Insertions and deletions within coding DNA usually lead to shifts in the reading frame during translation so change the protein produced or add a premature stop codon. If three bases are inserted/deleted at the same time then the frame won’t shift.
What are the effects of gene mutation: missense (nonsynonymous), nonsense and silent?
Missense: the new codon encodes a different amino acid; there is a change in amino acid sequence. Nonsense mutation: the new codon is a stop codon; there is premature termination of translation. Silent: the new codon encodes the same amino acid; there is no change in amino acid sequence.
What results from a single missense (nonsynonymous) mutation?
Sickle-cell anemia is caused by a change in only a single amino acid: Glu replaced by Val. The result is the misfolding of the hemoglobin subunit B-globin of which two copies cause sickle-cell anemia. In this condition: hemoglobin crystallizes in low levels of oxygen, causing the cell to collapse, oxygen is not carried through the body effectively, causing anemia, sickled cells block capillary vessels, causing pain and low oxygen levels.
What causes cystic fibrosis?
The mutant CTFR (cystic fibrosis transmembrane conductance regulator) protein is a result of an in-frame deletion of three nucleotides. The resulting protein does not fold properly. This results in abnormal secretions in the lungs, liver, pancreas, and other glands.
What can cause frame shifts?
Insertions and deletions
What are the types of gene mutation: forward, reverse and suppressors?
A forward mutation changes the wild type into a mutant phenotype, a reverse mutation restores the wild-type gene and the phenotype, a suppressor mutation occurs at a site different from that of the original mutation. And produces an individual that has both the original mutation and the suppressor mutation but has the wild-type phenotype
How do mutations occur?
The presence of mutagens can increase probability of mutation by a factor of 100 or more. Mutations are typically spontaneous. Mutagens can come from within cells or external e.g. chemicals or radiation.
What effect do X-rays have on mutations?
Can cause breaks in the sugar-phosphate backbone, in either one strand or both strands.
What effect does UV light have on mutations?
Can cause adjacent pyrimidines to cross-link, which most commonly leads to the formation of thymine dimers.
What do highly reactive chemicals tend to be?
Mutagenic, often because they add bulky side groups to the bases that hinder proper base pairing.
What can bleach or hydrogen peroxide cause?
Loss of a base, resulting in a gap in one strand of the DNA.
What can Tobacco smoke cause?
Add bulky side groups to the bases, resulting in improper base pairing.
How do substitution mutations occur?
Nonstandard base pairings can occur as a result of the flexibility in DNA structure. Wobble base pairings lead to a replicated error. Substitutions may also result from spontaneous chemical changes e.g. depurination. The apurinic site cannot provide a template for a complementary base on the newly synthesised strand. A nucleotide with the incorrect base is incorporated into newly synthesised strand. This is carried on leading to a permanent mutation.
How may insertions and deletions may result?
From strand slippage. Newly synthesised strand loops out, resulting in the addition of one nucleotide on the new strand, template strand loops out, resulting in the omission of one nucleotide on the strand.
How do mutations occur - Transposable elements?
Transposable elements, are DNA sequences that can jump in or out of genes, restoring its normal function. When a transposable element re-inserts elsewhere in the genome, it sometimes disrupts the function of a different gene. They are very common in genomes - as much as 45% of the human genome appears to be made up of transposable elements (DNA transposons and retrotransposons).
What is DNA repair?
Most DNA is repaired, DNA ligase - repairs broken backbone, DNA polymerase - corrects 99% of mistakes immediately. Subsequent processes decrease mutations further (by 1000 times). Mismatch repair, base-excision repair, nucleotide-excision repair, direct repair.
What is mismatch repair?
Mismatched bases and other DNA lesions are corrected by mismatch repair. Enzymes cut out a section of the newly synthesised strand of DNA and replace it with new nucleotides
What is base excision repair?
Glycosylase enzymes recognise and remove specific types of modified bases. The entire nucleotide is the removed, and a section of the polynucleotide strand is replaced.
What is nucleotide-excision repair?
Removes and replaces many types of damaged DNA that distort DNA structure (e.g. bulky side groups, thymine dimers). The two strands of DNA are separated, a section of the DNA containing the distortion is removed, DNA polymerase fills in the gap, and DNA ligase seals the filled-in gap.
What is direct repair?
Direct-repair mechanisms return an altered base to its correct structure without removing and replacing nucleotides
What are chromosomal level insertions/deletions?
A chromosome in which a region is present twice instead of once is said to contain a duplication. Usually, duplication of a region of the genome is less harmful than deletion of the same region. With a deletion, a region of the chromosome is missing. A deletion may result from a replication error or joining of breaks that may have occurred on either side of the deleted region. Because chromosome occur in homologous pairs, a deletion in one chromosome can persist in a population. However, in general the larger the deletion, the smaller the chance of survival.
What can chromosome level insertions/deletions cause?
Gene duplication within a chromosome. Duplication of whole chromosomes (aneuploidy) or whole genomes (polypoidy). The more copies of the gene a cell has in its genome, the more gene product can be produced simultaneously. The addition copy can gain mutations and become defunct (pseudogenes). Or accumulate beneficial mutations providing fuel for innovation: duplication and divergence creates new genes from old ones.
Chromosome level insertions/deletions - what can unequal crossing over produce?
Can produce large insertions and deletions. This kind of mutation is often the cause of colour blindness in humans. If homologous chromosomes misalign during crossing over, one crossover product contains an insertion, and the other has a deletion. Occasionally two X chromosomes in females don’t pair up correctly during meiosis and unequal crossing over takes place, producing one chromosome with an extra opsin gene and another with a missing gene, when a male inherits the X chromosome with a missing gene, red-green colour blindness results.
What are chromosome inversions?
Are common and usually don’t cause major problems as all genes are present (DNA can be transcribed in either direction). Explains why the order of genes along a chromosome can differ among closely related species. When the normal order of a block of genes is reversed, the result is an inversion. Inversions typically form when the region between two breaks in a chromosome is flipped before the breaks are repaired. Breaks often occur in non-coding DNA.
What is reciprocal translocation?
Reciprocal translocations join segments from nonhomologous chromosomes. Can cause problems with meiosis as gametes may end up with missing/additional gene copies. In the formation of reciprocal translocation, both chromosomes are broken and the terminal segements are exchanged before the breaks are repaired. In larger genomes, the breaks are likely to occur in noncoding DNA, so the breaks themselves do not usually disrupt gene function. Can cause problems with meiosis as chromosomes that have exchanged genetic material may not end up in the same gamete so gametes may have additional/missing copies of genes.
What are chromosome level mutations?
Important in evolution, e.g. HOX genes (body plans) - embryo development and regeneration. Very important in body plan evolution. Hox genes are found in all animals except sponges. Single hox gene cluster in an ancestor was duplicated twice early in vertebrate evolution by whole genome duplications to give four Hox gene clusters: Hoxa, Hoxb, Hoxc, Hoxd. Most mammals, amphibians, reptiles and birds have four hox clusters, while most teleost fish, including zebrafish and medaka, have seven or eight Hox gene clusters because of an additional genome duplication. In some teleost fish, such as salmon, an even more recent genome duplication occurred, doubling the seven or eight Hox gene clusters to give at least 13 clusters.
What are chromosome level mutations - gene duplication in humans?
AMY! gene produces amylase, more copies in people with culturally high starch diets.
What are mutation rates?
Mutation is a rare event for individual nucleotides. Certain nucleotides are prone to mutation (hotspots), differences between the sexes (more mutations in human sperm than eggs). Across species: highest among RNA viruses (less stable). The rates are nearly the same for all multicellular animals, including humans. Larger genomes + lots of cells = higher mutation numbers per genome. In humans, lots of mutations are tolerated because around 90% of nucleotides seem free to vary without harmful consequences. Only 2.5% of the human genome codes for protein.
What is genome size and complexity?
Highly variable, no relationship with organism complexity, due to non-coding DNA. And the use of gene regulation to produce different products from the genes. The disconnect between genome size and complexity is called the C-value paradox.
What is the C-value?
The amount of DNA in a reproductive cell, and the paradox is the apparent contradiction between the genome size and organismal complexity. The principal reason for large genomes among some eukaryotes is that their genomes contain large amounts of DNA that do not code for proteins, such as introns and DNA sequences that are present in many copies
What is polypoidy?
Having more than two sets of chromosome in the genome. Can create very larger genomes. Humans have two sets of 23 chromosomes. Many plants have 6 or 7 sets. One species of fern has 84 copies of 15 chromosomes, making 1260 chromosomes altogether. Large genomes can differ from small ones for a number of reasons.
What can polypoidy cause?
Instant speciation, common in plants: 40% of all flowering plants and 70-80% of grasses are polypoids. Also occurs in some invertebrates, fishes, amphibians and reptiles. No known examples in birds.
What is autopolypoidy?
Duplication within a species. Usually results in sterility (but may be able to reproduce asexually). E.g. domesticated bananas are triploid and sterile. Accidents of cell division giving rise to extra sets of chromosomes of the same species.
What is allopolypoidy?
Arises from hybridisation between two species. Offspring are sterile (but may be able to reproduce asexually). If polypoidy happens again, meiosis becomes possible.
