mutation and history

• Genetics - is the scientific study of genes and heredity of how certain qualities or traits are passed from parents to offspring as a result of changes in DNA sequence.
• What is heredity? Refers to the similarities between parents and offspring
• What is variation? is a difference, whether in the expression of somatic characters or in the elements of the germinal substance, exhibited among groups of organisms related by descent (ancestors).
• Mutation , therefore, is a random change in a gene or chromosome resulting in a new trait or characteristic that can be inherited.
• Mutation can be a source of beneficial genetic variation or it can be neutral or harmful in effect
• Gregor Mendel (1822-1884) Responsible for the Laws governing Inheritance of Traits
• Gregor Johann Mendel

  Austrian monk

  Studied the inheritance of traits in pea plants

  Developed the laws of inheritance

  Mendel's work was not recognized until the turn of the 20th century
• Between 1856 and 1863, Mendel cultivated and tested some 28,000 pea plants

  He found that the plants' offspring retained traits of the parents

  Called the “Father of Genetics"
• Mendel stated that physical traits are inherited as “particles”

  Mendel did not know that the “particles” were actually Chromosomes & DNA
• 1869 - Friedrich Miescher identified DNA. He isolated "nuclein," DNA with associated proteins, from cell nuclei. He was the first to identify DNA as a distinct molecule.
• 1900-1913 - Walter Sutton and Theodor Boveri chromosomal theory of inheritance states that genes are found at specific locations on chromosomes, and that the behavior of chromosomes during meiosis can explain
• Thomas Hunt Morgan - Genes on chromosomes - By examining thousands upon thousands of flies with a microscope, Morgan confirmed the chromosomal theory of inheritance: that genes are located on chromosomes like beads on a string, and that some genes are linked (meaning they are on the same chromosome and always inherited together).
• One of Morgan’s students, Alfred Sturtevant , created the first ever genetic map, a landmark event in genetics. -Genes linearly arranged on chromosomes & mapped –
• 1941- George Beadle and Edward Tatum related "gene" to enzyme & biochemical processes. They proved that our genetic code, our genes, govern the formation of enzymes. They exposed a type of mold to X-rays, causing mutations, or changes in its genes. They later succeeded in proving that this led to definite changes in enzyme formation.
• 1944 – Oswald Avery demonstrated that DNA was the genetic material. Oswald Avery did not win a Nobel Prize. The reason might be that Avery never publicly stated that a gene is made of DNA.
• 1953 - James Watson , Francis Crick , Rosalind Franklin & Maurice Wilkins • Lead to understanding of mutation and relationship between DNA and proteins at a molecular level
• 1959 – “Central Dogma”

  The central dogma of molecular biology explains the flow of genetic information, from DNA to RNA, to make a functional product, a protein
• From existing DNA to make new DNA (DNA replication)
• From DNA to make new RNA (transcription)
• From RNA to make new proteins (translation)
• Classical Genetics/Transmission Genetics

  • Concerned with the Chromosomal Theory of Inheritance, the concept that genes are located in a linear fashion on chromosomes
  • The relative position of genes can be determined by the frequencies of offspring in controlled mating.
  • It deals with transmission of genes from generation to generation and how genes recombine
• Molecular Genetics

  • It deals with the study of the genetic material: its structure, replication, and expression.
  • Here also the information revolution emanating from the discoveries of recombinant DNA techniques (genetic engineering) are examined.
  • It study the structure and function of genes at the molecular level
• Evolutionary Genetics

  • The study of the mechanisms of evolutionary changes, the changes of gene frequencies in populations.
  • It deals with the distribution and of genes (usually in mathematical terms) in population. However there are no sharp boundaries between these branches.
• The DNA molecule

  • Composed of 2 polymers of nucleotides
  • Polymers are oriented in antiparallel
  • Molecule resembles a spiral staircase of complementary base pairs
• Nucleotide structure of DNA

  Each nucleotide of DNA contains:

  • Deoxyribose
  • Phosphate
  • Nitrogen base (either A, G, C, T)
• Nucleotide structure of RNA Each nucleotide of RNA contains:

  • Deoxyribose
  • Phosphate
  • Nitrogen base (either A, G, C, U)

  contains Uracil instead of Thymine
• DNA structure

  • “Double helix” proposed by Watson and Crick (1953) •Antiparallel backbones

  • Complementary base pairing:

  • Adenine to Thymine • Cytosine to Guanine
• A chromosome constitutes an entire DNA molecule + protein

  • Protein = histones (any of various simple water soluble proteins that are rich in the basic amino acids lysine and arginine and are complex with DNA)
  • Supercoiled DNA in nucleosomes
  • Humans contain 46 such molecules (23 pairs) 44 somatic chromosomes 2 sex chromosomes (X +Y)
• • Genes constitute distinct regions on the chromosome
  • Each gene codes for a protein product

  -DNA -> RNA-> protein

  • Differences in proteins brings about differences between individuals and species
• How do chromosomes become double stranded? Answer: DNA replication

  • During the life of the cell, each chromosome of DNA makes a copy of itself
  • This must occur prior to cell division to insure each daughter cell gets a complete set
• Therefore, prior to dividing, any cell must first replicate DNA

  • Each single-stranded (SS) chromosome duplicates to become a double-stranded (DS) chromosome
  • Example: A human cell is formed with 46 SS chromosomes
  • Each chromosome replicates to produce 46 DS chromosome
• DNA replication occurs during the life of a cell = the Cell Cycle

  • DNA replicates (makes a copy of itself) to produce DS chromosomes
  • During this time, the cytoplasmic contents also duplicate
  • Spindle tubules form to aid in the process of cell division
  • Mitosis in body cells • Meiosis in sex cells
• A mutation is a permanent change in the DNA sequence of a gene. Mutations in a gene's DNA sequence can alter the amino acid sequence of the protein encoded by the gene.
• How does mutation happen? Like words in a sentence, the DNA sequence of each gene determines the amino acid sequence for the protein it encodes. The DNA sequence is interpreted in groups of three nucleotide bases, called codons. Each codon specifies a single amino acid in a protein.
• Substitution

  • is a mutation that exchanges one base for another (i.e., a change in a single "chemical letter" such as switching an A to a G). Such a substitution could:
  • 1.change a codon to one that encodes a different amino acid and cause a small change in the protein produced. For example, sickle cell anemia is caused by a substitution in the beta-hemoglobin gene, which alters a single amino acid in the protein produced
• Substitution

  • change a codon to one that encodes the same amino acid and causes no change in the protein produced. These are called silent mutations.
  • change an amino-acid-coding codon to a single "stop" codon and cause an incomplete protein. This can have serious effects since the incomplete protein probably won't function
• Insertion

  • are mutations in which extra base pairs are inserted into a new place in the DNA
• Deletion

  • are mutations in which a section of DNA is lost, or deleted.
• Frameshift

  • Insertions and deletions in protein-coding DNA, divided into three-base codons, can disrupt gene reading frames, leading to frame shifts. For instance, removing the first letter of each word in the sentence "The fat cat sat" results in a nonsensical interpretation due to the altered frame.
  • In frameshifts, a similar error occurs at the DNA level, causing the codons to be described incorrectly. This usually generates shorten proteins that are as useless as "hef atc ats at" is uninformative.
• What are the causes of mutations?

  • DNA fails to copy accurately The mutations crucial for evolution are mostly "naturally-occurring." When cells divide, they replicate DNA, occasionally resulting in imperfect copies, known as mutations, which introduce small differences from the original DNA sequence.
  • Exposure to mutagens like UV rays from the sun, chemicals (e.g., asbestos, cigarette smoke, nitrous acid), and high-energy radiation (e.g., medical X-rays) can break DNA strands, causing the loss of vital genetic material.