- A change in the sequence of nucleotides in an original DNA molecule
- Mutations are irreversible and the main cause of genetic variation (alleles)
- Mutations can cause changes in phenotype (ex. cystic fibrosis) or disorders
- Alterations in DNA can lead to changes in type or amount of protein produced
- DNA mutations can be positive, negative, or have no consequence; effect is determined by environmental conditions (usefulness of a mutated phenotype determined by natural selection)
Causes for Mutations
- Mutagens: radiation or chemicals that cause mutations → damage DNA (ex: deamination, double strand breaks)
- Carcinogens: mutagens that activate uncontrolled cell growth (cancer)
Environmental:
- UV light → forms dimers; radiation (X-rays); chemical mutagens
Internal:
- Errors in DNA replication, proofreading, or repair
Point Mutation: single or few nucleotide errors that include…
- Substitution: when DNA sequence contains an incorrect nucleotide instead of the correct one
- An amino acid substitution would always alter the primary structure of the protein, sometimes alter the tertiary structure of the protein and its biological activity
- Deletion: when a nucleotide is omitted from the nucleotide sequence → missing amino acid
- Deletions closer to start point of coding are more harmful
- Can occur when homologs don’t align properly
- An amino acid deletion will alter the primary, secondary, and tertiary structure → can’t fold properly → nonfunctional
- Insertion: when a nucleotide is added to nucleotide sequence
- Frameshift: result of deletion or insertion & occurs when the number of nucleotides is not divisible by three → alters the way that the genetic messages (mRNA codons) is read
- All other codons and amino acids (proteins) following mutation will be wrong
Effects of Point Mutations
- Point mutations may or may not have a significant phenotypic effect.
- Depends on whether amino acid had important chemical properties or part in proteins structure
- Might change the lvl of protein activity bcuz might substitute an amino acid in the active site.
- Depends on whether amino acid had important chemical properties or part in proteins structure
- Silent Mutation: when new codon still codes for the same amino acid
- More common when nucleotide substitution results in a change of last of 3 in a codon nucleotide
- Wobble Pairing: relaxed requirement for in the third position nucleotide
- Missense Mutation: when new codon codes for new amino acid
- Effect can be minor or result in the production of a protein that can’t fold into 3D shape and carry out function specific to shape
- Ex: hemoglobin protein that causes sickle-cell disease
- Nonsense Mutation: when new codon codes for stop codon
- Causes translation to be terminated early → resulting polypeptide is shorter → usually nonfunctional
Alterations to Chromosome Structure:
- Chromosomal aberrations occur when chromosome segments are changed, often result of crossing over errors
- Duplications: broken DNA fragment reattached as an extra to chromatid resulting in repeating segment
- Ex: Huntington’s disease is caused by insertion of multiple repeats of 3 nucleotides → codes for defective enzyme → death
- Deletions: during crossing over, one chromosome takes the WHOLE part of the other that crossed over and the other one is left shorter. Usually involve lots of genes
- Cri du chat: cry of the cat, caused by deletion in chromosome 5
- Inversion: piece of chromosome that is crossed over goes on backwards,
- So order of the genes matters (usually don’t express abnormalities as long as does not introduce duplications or deletions)
- Translocation: two nonhomologous chromosomes cross over which shouldn’t
- A parent with balanced translocation has chance to produce offspring with deletion or duplication
Notes
- Random mutations = source of new alleles = new phenotypes
- Deletion and duplication more common during crossing over when non-sister chromatids exchange unequal amounts of DNA
- Translocations during mitosis can cause some cancers
- Deletions and translocations more lethal
- Syndrome = not as lethal, group of traits caused by gene mutation or chromosome alteration
- Translocations and inversions don’t usually alter phenotype
Human Genetic Disorders
- Point Mutations:
- Sickle-cell disease: caused by nucleotide substitution → defective hemoglobin → blood cell to become sickle shaped in low-oxygen → cell does not flow through capillaries freely and oxygen not delivered throughout body
- Heterozygote generally without symptoms
- Tay-Sachs Disease: nucleotide insertion → lysosomes lack functional enzyme to break down glycolipids → fat accumulate → death
- Aneuploidy:
- Down Syndrome: when egg or sperm with with extra number 21 chromosome fuses with normal gamete → results in gamete with 3 copies of chromosome 21 (trisomy 21)
- Turner Syndrome: nondisjunction of the sex chromoosome (monosomy)
- Sperm will have either both sex chromosomes (XY) or none (O)
- When normal gamete fuses with (O) gamete will have zygote that is XO → sterile female (45 chromosomes) with abnormalities
- Although absence of single chromosome usually fatal, Y chromosome has such few genes that not too harmful
- Klinefelter Syndrome: occurs when XY or XX, produced as result of nondisjunction, combines with normal gamete to form XXY zygote (male with extra X)
- Only affects male → still male as long as you have Y chromosome with the SRY gene
- Explains how there can be male calico cats
- Might express female secondary sex characteristics
- Only affects male → still male as long as you have Y chromosome with the SRY gene
Transfer and Sharing of DNA: Prokaryotes Vs. Eukaryotes
Bacteria: 3 Methods of Transferring DNA
- Transduction
- Viruses that infect bacteria (bacteriophages) move DNA from one bacterium to another “by accident.”
- Transformation
- Bacteria takes in DNA from its environment,
- DNA often from other bacteria as a plasmid
Which can be copied and passed onto descendants
Conjugation
- DNA is transferred from one bacterium to another.
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- Donor cell (F+) uses pilus to transfer DNA from its cell to recipient cell (F-) → recipient becomes donor
- Usually DNA is in the form of a plasmid
- Donor cells typically act as donors because they have a chunk of DNA called the fertility factor (or F factor)
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F Factor: codes for the proteins that make up the sex pilus.
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- also contains a special site where DNA transfer during conjugation begins
Horizontal Gene Transfer:
- Horizontal Gene Transfer: transmission of DNA between different genomes
- Source of genetic variation in bacteria: horizontal gene transfer & mutations
- Bacteria use horizontal gene transfer used to spread virulent genes to harmless stains
- Bacteria use horizontal gene transfer used to spread virulent genes to harmless stains
- Vertical Gene Transfer transmission of genetic material from parents to offspring during reproduction
- Source of genetic variation in bacteria: horizontal gene transfer & mutations
Occurs in: eukaryotes, prokaryotes; chloroplasts, nucleus, & mitochondrion