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

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11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

29. 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.

30. 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.