Genetics and Evolution

Molecular Basis of Inheritance

Processing of pre-mRNA to mature mRNA

  • Central dogma of molecular biology
  • Transcription
    • RNA polymerase binds to DNA template strand
    • DNA unwinds and RNA synthesis begins
    • Promoter region determines which genes are transcribed
    • Transcription factors help RNA polymerase bind to the promoter
  • RNA processing
    • Addition of 5’ cap and 3’ poly-A tail
    • Removal of introns through RNA splicing
    • Assembly of exons to form mature mRNA
  • mRNA transport and translation
    • Mature mRNA is exported from the nucleus
    • Ribosomes bind to mRNA and begin translation
  • Regulation of gene expression
    • Control elements and enhancers
    • Transcription factors and repressors
    • Upregulation and downregulation of genes
  • Impact of mutations
    • Silent, missense, and nonsense mutations
    • Frameshift mutations
    • Effects on protein structure and function
  • Alternative splicing
    • Generation of multiple proteins from a single gene
    • Importance in increasing protein diversity
  • RNA interference
    • Regulation of gene expression through RNA degradation
    • Use in gene therapy and genetic research
  • RNA editing
    • Post-transcriptional modification of RNA nucleotides
    • Affects mRNA stability and protein function
  • Significance of mRNA processing
    • Ensures proper gene expression and protein production
    • Allows for regulation and diversity in gene expression
  1. Regulation of gene expression
  • Control elements and enhancers play a role in regulating gene expression.
  • Transcription factors bind to control elements and enhancers, helping RNA polymerase bind to the promoter.
  • Repressors, on the other hand, inhibit transcription by blocking RNA polymerase from binding to the promoter.
  • Upregulation occurs when there is an increase in the expression of a gene, while downregulation is the decrease in gene expression.
  • Examples of gene expression regulation include the lactose operon in bacteria and the lac repressor system.
  1. Impact of mutations
  • Mutations can have different effects on gene expression and protein function.
  • Silent mutations do not result in any change in the amino acid sequence.
  • Missense mutations lead to the substitution of one amino acid with another in the protein sequence.
  • Nonsense mutations introduce a premature stop codon, resulting in a truncated protein.
  • Frameshift mutations occur when nucleotides are inserted or deleted, causing a shift in the reading frame.
  • These mutations can have significant impacts on protein structure and function.
  1. Alternative splicing
  • Alternative splicing allows for the generation of multiple proteins from a single gene.
  • Different exons are combined in different ways to produce distinct mRNA transcripts.
  • This process increases protein diversity and can lead to different functions or variations in protein isoforms.
  • An example of alternative splicing is the production of different isoforms of the tropomyosin protein in muscle cells.
  1. RNA interference
  • RNA interference (RNAi) is a mechanism that regulates gene expression by degrading RNA molecules.
  • Short interfering RNAs (siRNAs) and microRNAs (miRNAs) bind to mRNA molecules and target them for degradation.
  • RNAi can be used in gene therapy to silence specific disease-causing genes.
  • It is also used in research to study gene function and gene regulation.
  • The discovery of RNAi led to the award of the Nobel Prize in Physiology or Medicine in 2006.
  1. RNA editing
  • RNA editing is a post-transcriptional modification that alters nucleotides in RNA molecules.
  • This process can change the identity of individual bases, such as converting adenosine (A) to inosine (I).
  • RNA editing can affect mRNA stability and protein function.
  • An example of RNA editing is the conversion of apolipoprotein B mRNA, which produces two different isoforms in the liver and intestines.
  1. Significance of mRNA processing
  • mRNA processing ensures proper gene expression and protein production.
  • It helps to remove introns and join exons to form mature mRNA.
  • The addition of a 5’ cap and a 3’ poly-A tail protects mRNA and aids in its transport out of the nucleus.
  • Alternative splicing allows for the production of different protein isoforms from a single gene.
  • mRNA processing contributes to the regulation and diversity of gene expression.
  1. Central dogma of molecular biology
  • The central dogma states that genetic information flows from DNA to RNA to protein.
  • DNA serves as the template for the synthesis of RNA molecules through the process of transcription.
  • RNA molecules, including messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA), are involved in protein synthesis.
  • Translation is the process of decoding the genetic information in mRNA to produce proteins.
  • The central dogma provides the basis for understanding the molecular basis of inheritance.
  1. Transcription
  • Transcription is the process by which an RNA molecule is synthesized from a DNA template strand.
  • RNA polymerase binds to the DNA template and synthesizes an RNA molecule in the 5’ to 3’ direction.
  • The promoter region determines which genes are transcribed and where transcription begins.
  • Transcription factors assist RNA polymerase in binding to the promoter and initiating transcription.
  • Transcription occurs in the nucleus of eukaryotic cells.
  1. RNA processing: Addition of 5’ cap and 3’ poly-A tail
  • After transcription, the pre-mRNA molecule undergoes several modifications to become mature mRNA.
  • The addition of a 5’ cap involves the attachment of a modified guanine nucleotide to the 5’ end of the pre-mRNA.
  • The 5’ cap protects mRNA from degradation and assists in its export from the nucleus.
  • The addition of a 3’ poly-A tail involves the attachment of multiple adenine nucleotides to the 3’ end of the pre-mRNA.
  • The poly-A tail also protects mRNA from degradation and aids in the initiation of translation.
  1. RNA processing: Removal of introns through RNA splicing
  • Pre-mRNA molecules contain both coding regions (exons) and non-coding regions (introns).
  • RNA splicing is the process by which introns are removed and exons are joined together to form mature mRNA.
  • A spliceosome, composed of small nuclear ribonucleoproteins (snRNPs), carries out the splicing process.
  • Alternative splicing allows for different combinations of exons to be included or excluded in the final mRNA transcript.
  • The splicing process contributes to the diversity of gene expression and the protein repertoire.
  1. mRNA transport and translation
  • After mRNA processing, mature mRNA is exported from the nucleus to the cytoplasm.
  • In the cytoplasm, ribosomes bind to the mRNA molecule and initiate the process of translation.
  • Translation involves the synthesis of a protein using the genetic information encoded in the mRNA.
  • The ribosome reads the mRNA in codons, which consist of three nucleotides.
  • Each codon specifies a particular amino acid or signals the end of translation.
  1. Regulation of gene expression in prokaryotes
  • In prokaryotes, gene expression regulation occurs at the transcriptional level.
  • The lac operon in E. coli is an example of gene regulation in prokaryotes.
  • The lac operon consists of the lacZ, lacY, and lacA genes, along with an operator and a promoter.
  • When lactose is present, it binds to the lac repressor protein and prevents it from binding to the operator.
  • This allows RNA polymerase to bind to the promoter and transcribe the lac genes.
  1. Gene regulation in eukaryotes
  • In eukaryotes, gene regulation is more complex and occurs at multiple levels.
  • Transcription factors, enhancers, and silencers play important roles in regulating gene expression.
  • Chromatin structure and DNA methylation can also affect gene expression.
  • Epigenetic modifications, such as histone acetylation and DNA methylation, can be heritable and influence gene activity.
  • Gene regulation in eukaryotes allows for cell differentiation and the development of specialized tissues.
  1. Epigenetics and inheritance
  • Epigenetic modifications can be inherited and influence gene expression patterns.
  • DNA methylation and histone modifications can be passed on from one generation to the next.
  • Epigenetic changes can be influenced by environmental factors and affect gene activity.
  • Examples of epigenetic inheritance include genomic imprinting and X-chromosome inactivation in females.
  • Epigenetic changes can contribute to phenotypic variation and may play a role in the development of diseases.
  1. Genetic diversity and evolution
  • Genetic diversity is the variation in the genetic material of a population or species.
  • Genetic diversity is important for the survival and adaptation of populations.
  • Factors that contribute to genetic diversity include mutation, recombination, and gene flow.
  • Genetic diversity allows for adaptation to changing environments and provides the raw material for evolution.
  • The loss of genetic diversity can increase the risk of extinction and reduce the ability of populations to adapt.
  1. Hardy-Weinberg equilibrium
  • The Hardy-Weinberg equilibrium is a principle that describes the genetic makeup of a population in the absence of evolutionary forces.
  • The equilibrium assumes that the population is large, mating is random, mutation is negligible, migration is absent, and selection is not occurring.
  • The Hardy-Weinberg equation allows us to calculate the frequencies of alleles and genotypes in a population.
  • If a population deviates from the Hardy-Weinberg equilibrium, it suggests that some evolutionary forces are at play, such as natural selection or genetic drift.
  1. Genetic drift
  • Genetic drift is a random fluctuation in allele frequencies in a population.
  • Genetic drift can occur due to random events, such as the death of individuals or the colonization of new habitats.
  • Genetic drift is more pronounced in small populations and can lead to the fixation or loss of alleles.
  • Genetic drift can reduce genetic diversity and increase the genetic differentiation between populations.
  • The founder effect and the bottleneck effect are examples of genetic drift.
  1. Natural selection
  • Natural selection is a process by which individuals with favorable traits are more likely to survive and reproduce.
  • It is one of the main mechanisms driving evolution.
  • Natural selection acts on heritable traits, leading to changes in allele frequencies over time.
  • Three types of natural selection are directional selection, stabilizing selection, and disruptive selection.
  • Natural selection can result in adaptation, where individuals become better suited to their environment.
  1. Sexual selection
  • Sexual selection is a type of natural selection that acts on traits related to mating success.
  • It can lead to the evolution of elaborate male traits and behaviors, such as peacock feathers or bird songs.
  • Intrasexual selection involves competition between members of the same sex for access to mates.
  • Intersexual selection occurs when members of one sex choose mates based on certain traits or behaviors.
  • Sexual selection can lead to the evolution of exaggerated traits that may not necessarily enhance survival.
  1. Coevolution
  • Coevolution refers to the reciprocal evolutionary changes that occur between two or more species.
  • It can be a result of mutualistic interactions, such as the coevolution between flowers and pollinators.
  • Antagonistic interactions, such as predator-prey relationships, can also drive coevolution.
  • Coevolution can lead to adaptations in both species, enhancing their fitness in the context of their interactions.
  • Examples of coevolution include the arms race between predators and prey and the coevolution between parasites and their hosts.