Genetics and Evolution

Molecular Basis of Inheritance

Contribution of Scientists in search of genetic material

• Friedrich Miescher (1869)

  • Isolated a chemical substance from the nucleus of WBCs
  • Named it “nuclein”

• Richard Altmann (1889)

  • Coined the term “nucleic acid”

• Phoebus Levene (1919)

  • Determined the basic structure of nucleotides

• Oswald Avery, Colin MacLeod, and Maclyn McCarty (1944)

  • Identified DNA as the genetic material

• Alfred Hershey and Martha Chase (1952)

  • Confirmed Avery’s conclusion with bacteriophage experiments

• Watson and Crick (1953)

  • Proposed the double helical structure of DNA
  • Published the model based on X-ray crystallography by Rosalind Franklin and Maurice Wilkins

• Meselson and Stahl (1958)

  • Conducted the famous DNA replication experiment using isotopes

• Matthew Meselson and Franklin Stahl

  • Demonstrated that DNA replication is semi-conservative

• Marshall Nirenberg and Har Gobind Khorana (1961)

  • Discovered the genetic code

• Kary Mullis (1983)

  • Developed the Polymerase Chain Reaction (PCR) technique

DNA Replication

• DNA replication is the process of copying DNA molecules to create identical copies.
• It occurs during the S phase of the cell cycle.
• The process involves three main steps: initiation, elongation, and termination.
• Initiation begins with the unwinding of the DNA helix by helicase enzymes.
• DNA polymerase enzyme adds nucleotides to the original strand in the 5’ to 3’ direction.
• Leading strand synthesis is continuous, while lagging strand synthesis occurs discontinuously in small fragments called Okazaki fragments.
• RNA primase synthesizes RNA primers to initiate the synthesis of each Okazaki fragment.
• DNA ligase joins the Okazaki fragments together to form a continuous strand.

Genetic Mutations

• Genetic mutations are permanent changes in the DNA sequence.
• They can occur due to various factors like chemicals, radiation, errors during DNA replication, etc.
• Types of mutations include point mutations, insertions, deletions, and frameshift mutations.
• Point mutations involve the substitution of one nucleotide for another.
• Insertions involve the addition of one or more nucleotides to the DNA sequence.
• Deletions involve the removal of one or more nucleotides from the DNA sequence.
• Frameshift mutations occur when the reading frame of the genetic code is disrupted due to insertions or deletions.

Types of Genetic Mutations

• Silent mutations do not result in any change in the amino acid sequence due to the degeneracy of the genetic code.
• Missense mutations result in the substitution of one amino acid for another, potentially affecting the protein’s function.
• Nonsense mutations introduce a premature stop codon, leading to the truncation of the protein.
• Frameshift mutations cause a shift in the reading frame, altering the entire amino acid sequence downstream.
• Chromosomal mutations involve changes in the structure or number of chromosomes, such as deletions, duplications, inversions, and translocations.

Genotype and Phenotype

• Genotype refers to the specific genetic makeup of an organism, including both the dominant and recessive alleles.
• Phenotype refers to the observable physical characteristics or traits displayed by an organism.
• Genotype determines the potential range of phenotypes that an organism can display.
• Phenotype is influenced by both the genotype and environmental factors.
• Some traits are controlled by a single gene (monogenic traits), while others are influenced by multiple genes (polygenic traits).
• Examples of monogenic traits include Mendelian disorders like cystic fibrosis and sickle cell anemia.

Mendelian Inheritance

• Mendelian inheritance refers to the patterns of inheritance discovered by Gregor Mendel.
• Mendel’s laws include the law of segregation and the law of independent assortment.
• The law of segregation states that alleles segregate during gamete formation, with each gamete receiving only one copy of each gene.
• The law of independent assortment states that alleles for different genes segregate independently of each other during gamete formation.
• Mendelian traits are inherited following predictable patterns, such as dominant-recessive or codominant inheritance.

Pedigree Analysis

• Pedigree analysis is the study of inheritance patterns in families to determine the mode of inheritance of genetic traits.
• Pedigrees use symbols to represent individuals and their relationships.
• Male individuals are represented by squares, and female individuals are represented by circles.
• Horizontal lines connect couples, and vertical lines connect parents to their offspring.
• The presence or absence of a trait is indicated by shading or color.
• Pedigrees can help identify the mode of inheritance (autosomal dominant, autosomal recessive, X-linked, etc.) and determine the risk of inheriting a particular trait.

Genetic Disorders

• Genetic disorders are conditions caused by mutations or abnormal changes in the DNA sequence.
• They can be inherited or occur due to spontaneous mutations.
• Examples of genetic disorders include:
  • Cystic fibrosis: a monogenic disorder affecting the respiratory and digestive systems.
  • Huntington’s disease: an autosomal dominant disorder affecting the nervous system.
  • Down syndrome: a chromosomal disorder caused by an extra copy of chromosome 21.
  • Hemophilia: an X-linked disorder resulting in impaired blood clotting.
• Genetic disorders can have varying degrees of severity and may require different treatment approaches.

Genetically Modified Organisms (GMOs)

• Genetically modified organisms (GMOs) have been genetically altered to possess specific traits.
• Genetic modification can involve the transfer of genes from one organism to another.
• GMOs have been developed for various purposes, including increasing crop yield, enhancing nutritional content, and improving resistance to pests and diseases.
• While GMOs offer potential benefits, controversies exist regarding their safety, ecological impact, and ethical concerns.
• Regulatory authorities monitor the development and commercialization of GMOs to ensure safety and proper labeling.

Population Genetics

• Population genetics studies the distribution and change of genetic variation within populations over time.
• It analyzes how genetic traits are inherited and how they change within and between populations.
• Factors that influence population genetics include genetic drift, gene flow, mutations, natural selection, and non-random mating.
• Genetic drift refers to the random changes in allele frequency due to chance events.
• Gene flow occurs when individuals migrate between populations, leading to the exchange of genetic material.
• Natural selection acts on individuals with advantageous traits, increasing their chances of survival and reproduction.

Hardy-Weinberg Equilibrium

• Hardy-Weinberg equilibrium is a mathematical model that predicts allele and genotype frequencies in a population over generations.
• It assumes a population that is large, randomly mating, not undergoing genetic drift, gene flow, mutation, or natural selection.
• The Hardy-Weinberg equation is: p^2 + 2pq + q^2 = 1, where p represents the frequency of the dominant allele and q represents the frequency of the recessive allele.
• This equation allows us to calculate the expected genotype frequencies in a population.
• Deviations from Hardy-Weinberg equilibrium can indicate the presence of evolutionary forces such as selection, migration, or mutation.

Gene Expression

• Gene expression is the process by which the information encoded in genes is used to create functional gene products such as proteins.
• Gene expression involves two main steps: transcription and translation.
• Transcription occurs in the nucleus, where the DNA sequence is converted into an RNA molecule (mRNA) by RNA polymerase.
• mRNA is then transported to the cytoplasm where translation takes place.
• Translation involves the synthesis of proteins using the information encoded in mRNA.

Transcription

• Transcription is the process of producing an RNA molecule from a DNA template.
• It involves several steps:
  • Initiation: RNA polymerase binds to the promoter region of the DNA and starts synthesizing mRNA.
  • Elongation: RNA polymerase moves along the DNA template, adding complementary RNA nucleotides.
  • Termination: RNA polymerase reaches a termination sequence, which signals the end of transcription.

Translation

• Translation is the process of synthesizing proteins from mRNA.
• It occurs in the ribosomes and involves three main steps:
  • Initiation: The ribosome binds to the mRNA and identifies the start codon (usually AUG).
  • Elongation: Amino acids are added to the growing polypeptide chain according to the codons on the mRNA.
  • Termination: The ribosome reaches a stop codon (UAA, UAG, or UGA), and the polypeptide chain is released.

Genetic Code

• The genetic code is a set of rules that determines how the nucleotide sequence of mRNA is converted into the amino acid sequence of a protein.
• The genetic code is universal, meaning that it is the same in all organisms.
• Each three-nucleotide sequence on mRNA is called a codon and corresponds to one amino acid.
• There are 64 possible codons, including start and stop codons.
• The genetic code is degenerate, meaning that multiple codons can code for the same amino acid.

Mutation and Genetic Variation

• Mutations are responsible for genetic variation, which is essential for evolution and adaptation.
• Mutations can be caused by errors during DNA replication, exposure to mutagens (chemicals or radiation), or spontaneous changes.
• Mutations can have different effects on the organism:
  • Neutral mutations have no significant effect on the organism.
  • Beneficial mutations provide an advantage and can increase an organism’s fitness.
  • Harmful mutations can lead to genetic disorders or reduce an organism’s fitness.

DNA Repair Mechanisms

• Cells have various DNA repair mechanisms to fix mutations and maintain genome stability.
• Three primary mechanisms are:
  • Proofreading: DNA polymerase checks for mistakes during DNA replication and corrects them.
  • Mismatch repair: Repair proteins detect and fix mismatched base pairs that occur after DNA replication.
  • Nucleotide excision repair: Repair enzymes remove damaged or abnormal nucleotides and replace them with new ones.

Regulation of Gene Expression

• Gene expression is tightly regulated to ensure cells produce the right amount of proteins at the right time.
• Regulation can occur at various levels, including:
  • Transcriptional regulation: Control of transcription initiation through the binding of regulatory proteins to DNA.
  • Post-transcriptional regulation: Regulation of mRNA processing, transport, and stability.
  • Translational regulation: Control of mRNA translation into proteins.
  • Post-translational regulation: Modification of proteins after translation to activate or inactivate them.

Epigenetics

• Epigenetics refers to heritable changes in gene expression that do not involve changes in DNA sequence.
• Epigenetic modifications can be influenced by environmental factors and can be passed on to future generations.
• Examples of epigenetic modifications include DNA methylation, histone modification, and non-coding RNA.
• Epigenetic changes can have significant impacts on gene expression patterns and disease susceptibility.

Biotechnology

• Biotechnology is the use of biological systems, organisms, or their derivatives for technological applications.
• It has revolutionized various fields, including medicine, agriculture, and environmental science.
• Examples of biotechnological applications include:
  • Gene therapy to treat genetic disorders by introducing normal genes into affected individuals.
  • Genetically modified crops with improved resistance to pests, diseases, or environmental conditions.
  • Production of therapeutic proteins using genetically engineered microorganisms.

Ethical Considerations in Genetics and Biotechnology

• Genetic and biotechnological advancements raise important ethical considerations.
• Examples of ethical issues include:
  • Privacy and confidentiality of genetic information.
  • Informed consent for genetic testing and genetic interventions.
  • Equity in access to genetic technologies and their potential benefits.
  • Environmental impacts and risks associated with genetically modified organisms.
• Ethical frameworks and regulations help guide responsible practices in the field of genetics and biotechnology.