Understanding Gene Mutations

Mutations

• A mutation results from a change in DNA, leading to a non-functioning protein or, in some cases, a protein that gives the organism an advantage.
• Alleles of genes are a result of mutation.

Gene Mutations

• Gene mutations occur randomly during DNA replication, involving a change in the base sequence of the DNA.
• Exposure to mutagenic agents, such as high energy radiation (UV light), ionizing radiation (Gamma rays and X rays), and chemicals (carcinogens like mustard gas and cigarette smoke), increases the likelihood of random mutations.
• Mutations can alter the amino acid sequence in the encoded polypeptide, affecting the hydrogen and ionic bonds
• May affect the 3D shape of the protein with a non-functioning protein as a possible result.
• Mutations aren't always harmful or impactful
• Some mutations lead to beneficial characteristics, like antibiotic resistance in bacteria.
• Neutral mutations involve DNA change, however they don't impact the produced protein

Impact of Gene Mutations

• Gene mutations can involve a base being deleted or substituted.
• TAC CCA AGT GGC is the original DNA sequence
• TAC ACA AGT GGC represents a base substitution mutation
• TAC CAA GTG GC represents a base deletion mutation
• A base substitution can be 'silent', with the new codon coding for the same amino acid due to the degenerate nature of the genetic code.
• Base deletions lead to a frameshift, changing all subsequent codons and resulting in multiple incorrectly coded amino acids.

Types of Gene Mutations

Addition

• Involves adding an extra base to the sequence.
• Original sequence: TAC TTC AGG TGG
• Mutation: TAC ATT CAG GTG G
• Addition causes a frameshift because all subsequent codons are altered
• Alteration can result in non-functioning protein with different amino acids coded.

Deletion

• The deletion of a base in a sequence:
• Original: TAC TTC AGG TGG
• Mutation: TAC TCA GGT GG
• A frameshift will occur to the left as a result
• This causes a different polypeptide chain which leads to a non-functioning protein.

Substitution

• One base is changed for a different base while maintaining the number of bases which prevents a frameshift.
• Due to the fact it's degernate this results in only one codon changing, it may still code for the same amino acid and therefore have no impact.
• Original: TAC TTC AGG TGG
• Mutation: TAC ATC AGG TGG

Control of Transcription

• In eukaryotes, transcription of target genes can be stimulated or inhibited when specific transcriptional factors move from the cytoplasm into the nucleus.
• Turning on/off particular genes in a cell enables specialization.
• In prokaryotes, not all proteins are constantly produced, to preserve resources
• The lac operon in E. coli: a sequence of 3 genes collectively aiding with lactose digestion
• Bacteria favor glucose digestion due to lower energy requirements, digesting lactose only when glucose is absent.
• Proteins produced by the lac operon are only needed if glucose is absent and lactose is present,
• Transcription of these genes is regulated to match this demand.
• Two molecules turn the operon on and off: the lac repressor and the catabolite activator protein (CAP).
• The lac repressor senses the presence of lactose through allolactose.
  • Allolactose usually binds to the operon to prevent transcription; however, the lac repressor detaches when lactose is present, allowing transcription.
  • Lactose blocks operon transcription but stops acting as a repressor when lactose is present.
• Catabolite activator protein (CAP) senses glucose presence through cAMP.
  • CAP initiates lac operon transcription when glucose levels are low.

Transcriptional Factors

• Transcription occurs when a molecule from the cytoplasm enters the nucleus and binds to the DNA by transcription factors.
• Transcription factors bind to different base sequences on DNA to initiate gene transcription.
• Once bound the transcription of genes will begin and creating the mRNA molecule for that gene which is translated to produce protein.
• The gene is inactive without this binding.

Oestrogen

• An example of a steroid hormone that can initiate transcription.
• Binds to a receptor site on a transcriptional factor, changing its shape slightly to become complementary to DNA to initiate transcription

Epigenetics

• Epigenetics is how the environment influences and interacts with the genome.
• Factors such as diet, stress, and toxins can add chemical tags to the DNA, controlling gene expression in eukaryotes.
• Epigenetics involves heritable changes in gene function without altering the DNA base sequence.
• Epigenetic inheritance, along with DNA inheritance, takes place.
• The epigenome: the layer of chemical tags on the DNA, impacting the shape of the DNA-histone complex.
• The epigenome determines whether DNA is tightly wound (not expressed) or unwound (expressed).
• Tightly wound DNA prevents transcription factors from binding.
• The epigenome, due to changes in the environment, can inhibit transcription.

Post-Transcriptional Changes

mRNA Modification

• The newly synthesized strand of mRNA is called pre-mRNA before modification.
• Key modifications remove introns and add protective caps to protect mRNA from degradation by enzymes in the cytoplasm.
• The second modification is the removal of the 'junk DNA' or introns by a protein called a spliceosome in spicing.
• mRNA is spliced in varying ways, to where a single gene can result in multiple proteins via alternative splicing.
• Alternative splicing is why humans have 90,000 proteins and 23,000 genes, meaning the utilization of the extra proteins is why the introns are important.
• Some proteins need to be activated by other molecules after translation.
• Cyclic AMP can bind to protein kinases, which activates them to catalyze reactions, shown in the second messenger model for glucose regulation.

Homeobox Gene Sequence and Hox Genes

• Plants, animals, and fungi use homeobox gene sequences to control body development, regulating the expression of other genes involved in body formation during early embryonic development.
• Hox genes are a type of homeobox gene found in metazoan.

Control of Body Form

• Mitosis and apoptosis are important in controlling body form.
• Cell cycle control: genes ensure new cells are made as needed for growth and repair, preserving energy and preventing tumor formation.
  • The tumor suppressor gene makes cell cycle stopping proteins, proto-oncogenes initiate the cell cycle.
  • Apoptosis occurs if a cell error is detected or if it is too old, destroying the cell and recycling resources.
• The control of mitosis and apoptosis: respond to internal and external stimuli, such as stress.

Genetic Variation

• Mutations, meiosis, and random gamete fertilization during sexual reproduction introduce genetic variation.
• Competition for resources and the impact of disease/predators result in natural selection where individuals in a population show a wide range of phenotype (genetic and environmental factors).
• Mutation is the primary source of genetic variation.
• Predation, disease, and competition: selection pressures with organisms of phenotypes w/ selective advantages survive to reproduce.

Selective Advantage

• Individuals best suited to their environment pass on their alleles.
• Artificial selection manipulates the gene pool, favoring specific alleles.
• Selective breeding can lead to genetic disorders.
• Selective advantage: a phenotype that increases survival and reproduction.
• Differential reproductive success leads to changes in allele frequencies in a gene pool which leads to evolution.
• Disruptive selection: When individuals which contain the alleles coding for either extreme trait are more likely to survive and pass on their alleles
• Increased allele frequency for extreme traits, reduced frequency for middling traits.
• Disruptive selection can lead to speciation

Inheritance Key Terms

• Genotype - The genetic constitution of an organism (the alleles it has for a gene).
• Phenotype - The expression of the genes and its interaction with the environment.
• Homozygous - A pair of homologous chromosomes carrying the same alleles for a single gene.
• Heterozygous - A pair of homologous chromosomes carrying two different alleles for a single gene.
• Recessive allele - An allele only expressed if no dominant allele is present.
• Dominant allele - An allele that will always be expressed in the phenotype.
• Codominant - Both alleles are equally dominant and expressed in the phenotype.
• Multiple Alleles - More than two alleles for a single gene.
• Sex-linkage - A gene whose locus is on the X chromosome.
• Autosomal Linkage - Genes that are located on the same chromosome (not the sex-chromosomes).
• Epistasis - When one gene modifies or masks the expression of a different gene at a different locus.
• Monohybrid - Genetic inheritance cross of a characteristic determined by one gene.
• Dihybrid - Genetic Inheritance cross for a characteristic determined by two genes.

Blood Groups

• Displays both codominance and multiple alleles
• Blood group phenotype can be A, B, AB, or O; referring to the specific protein, or antigen, found on the surface of red blood cells.
• Only one gene codes for this phenotype
• Allele IA codes for the A antigen and dominating
• Allele IB codes for the B antigen, and is also dominant
• Allele IO codes for no anitgen, and is recessive
• Since alleles IA and IB are dominating, they're both expressed, resulting in the AB phenotype

Sex-Linked Inheritance

• The X chromosome is larger than the Y, containing a larger non-sex-determining region.
• Genes linked to haemophilia, Duchenne muscular dystrophy, and red-green colorblindness can be found.

Autosomal Linkage Inheritance

• Humans have 23 chromosome pairs
• Autosomal linkage studies on non-sex-chromosome genes.

Epistasis

• Epistasis occurs when one gene masks the expression of another gene.
• Coat color in Labrador retrievers
  • Two genes control coat color
  • Gene 1 determines pigment production with Allele E (pigment produced) and e (no pigment produced).
  • Gene 2 influences pigment concentration (Allele B for high concentration and b for lower concentration).
  • Gene 1 can mask gene 2's expression when the alleles are e (no coding for pigment production).

Hardy-Weinberg Principle

• Mathematical model to predict allele frequencies within a population.
• Assumes no changes in allele frequencies between generations (no deaths, births, or migration) with an imperfect model.
• The frequency of alleles, genotypes, and phenotypes can be calculated: p^2 + 2pq + q^2 = 1
• Use with the equation: p + q = 1
  • p = the frequency of one (usually the dominant) allele
  • q = the frequency of the other (usually recessive) allele of the gene
  • p^2 = The frequency of the homozygous dominant genotype
  • 2pq = The frequency of the heterozygous genotype
  • q^2 = The frequency of the homozygous recessive genotype

Speciation

• The process that results in the creation of new species when one population of the same species becomes reproductively isolated (can't interbreed).
• This can lead to accumulating different genetic differences in their gene pools to the extent of not producting fertile offspring and classified as two different species.
  • Can occur geographically (allopatric) or due to reproductive mechanism changes (sympatric).

Allopatric Speciation

• Populations geographically separated, leading to reproductive isolation with genetic variation arising.
• Geographic isolation occurs due to physical barriers like mountain ranges or bodies of water.
• Populations still accumulate different mutations over time, to adapt to their respective environments.
• The two populations are so genetically distinct that they can no longer reproduce to produce fertile offspring, leading to their classification as two different species,

Sympatric Speciation

• Populations are reproductively isolated due to behavioral differences with no geographical barriers but unable to reproduce together.
• Affects reproductive behavior like courting and fertility at different times of year from mutation among the population.
• Over time, isolated populations will accumulate different mutations that are so distinct that they can no longer produce fertile offspring, classifying them as two distinct species.

Genetic Drift

• A change in allele frequency within a population between generations.
• Significant genetic drift results in evolutionary change.
• Smaller populations experience a larger proportionally in allele frequency, which makes evolution occur rapidly in populations.

Genetic Bottlenecks and the Founder Effect

• Two processes with different causes that have the same impact.
• Genetic bottlenecks
  • An event kills almost all of a population, leaving only a few individuals alive, limiting the gene pool.
• Founder Effect:
  • A few individuals from an existing population relocate to an isolated area, starting a new population with a limited gene pool.