M04-Genetics

Genetics

Unknown prior to 1953

Almost all of the genetic code is shared by all organisms.

  

Watson and Crick's Discovery of the Double Helix

The celebrated partnership that resulted in the determination of the physical structure of DNA began soon after a 23-year-old American named James D. Watson journeyed to Cambridge University, where Englishman Francis Crick was studying protein structure with a technique called X-ray crystallography . While visiting the laboratory of Maurice Wilkins at King's College in London, Watson saw an X-ray crystallographic photograph of DNA, produced by Wilkins's colleague Rosalind Franklin. The photograph clearly revealed the basic shape of DNA to be a helix (spiral). On the basis of Watson's later recollection of the photo, he and Crick deduced that the diameter of the helix was uniform. The thickness of the helix suggested that it was made up of two polynucleotide strands-in other words, a double helix.  Using wire models, Watson and Crick began trying to construct a double helix that would conform both to Franklin's data and to what was then known about the chemistry of DNA. After failing to make a satisfactory model that placed the sugar-phosphate backbones inside the double helix, Watson tried putting the backbones on the outside and forcing the nitrogenous bases to swivel to the interior of the molecule. It occurred to him that the four kinds of bases might pair in a specific way. This idea of specific base pairing was a flash of inspiration that enabled Watson and Crick to solve the DNA puzzle.

The four nucleotides found in DNA differ only in their nitrogenous bases.  At this point, the structural details are not as important as the fact that the bases are of two types. Thymine (T) and Cytosine (C) are single-ring structures. Adenme (A) and Guanme (G) are larger, double-ring structures.  RNA has the nitrogenous base Uracil (U) instead of thymine ( uracil is very similar to thymine). RNA also contains a slightly different sugar than DNA (ribose instead of deoxyribose). Other than that, RNA and DNA polynucleotides have the same chemical structure.

Nucleic acids are information storage molecules that provide the directions for building proteins.  Each nucleotide consists of three parts: a sugar, a phosphate & a nitrogenous base.  There are two types of nucleic acids: DNA and RNA  The inherited genetic consists of giant molecules of DNA. Within the DNA are genes, specific stretches of DNA, that program the sequences of proteins. These instructions in chemical code must be translated from "nucleic acid language" to "protein language." The RNA molecules help translate.  DNA is a strand of nucleotides linked into a backbone, with appendages in a specific sequence of the four bases, abbreviated A, G , C, and T.  A double helix consists of two DNA stands held together by bonds between bases.  The bonds are individually weak – The strands zip together with a cumulative strength that gives the double helix it’s stability. Base pairing is specific: A always pairs with T; G always pairs with C.  RNA differs from DNA as it has nitrogenous base Uracil (U) in place of (T).   RNA is usually found in single strand only while DNA is a double strand helix.

Cells are of two basic types: prokaryotic and eukaryotic- Prokaryotic cells lack a nuclear membrane and possess no membrane bounded cell organelles, whereas eukaryotic cells are more complex, possessing a nucleus and membrane bounded organelles such as chloroplasts and mitochondria.

 

Prokaryotic and Eukaryotic cells                                         Microscopes enabled search

The first Genetic Code was probably RNA, not DNA

            In 1981 it was found  that RNA  can excise 400 nucleotides in the absence of any protein.  Called ribozymes, these RNA molecules can cut out parts of their own sequences, connect some RNA molecules together, replicate others.   The discovery of ribozymes suggests that the original genetic material was RNA.

            Self-replicating ribozymes probably first arose between 3.5 billion and 4 billion years ago.   Early life was an RNA world, with RNA molecules serving both as carriers of genetic information and as catalysts that drove the chemical reactions needed to sustain and perpetuate life. These catalytic RNA’s may have acquired the ability to synthesize protein-based enzymes, which are more efficient catalysts; with enzymes taking over more and more of the catalytic functions, RNA took on the role of information storage and transfer, eventually replacing RNA as the primary carrier of genetic

 

  

Genetic information is transferred from DNA to RNA to protein -  Genetic information is first transcribed from DNA into RNA, and then RNA is translated into the amino acid sequence of a protein.

Memory  DNA is the memory bank, there are four types of nucleotides (memory bits), which differ in their nitrogenous bases (A, T, C, and G). The same is true for RNA, although it has the base U instead of T.

Codons  (biologist term for word). The genetic instructions for the amino acid sequence of a polypeptide chain are written in DNA and RNA as a series of three-base words called codons.

Words   Triplets of bases are the "words" of uniform length that specify the amino acids. There can be 64 possible code words of this type (shown below), more than enough to specify the 20 amino acids; enough triplets to allow more than one coding for each amino acid. For example, the base triplets AAT and AAC could both code for the same amino acid and do.

Language  DNA language is written as a linear sequence of nucleotide bases as illustrated above  Specific sequences of bases, each with a beginning and an end, make up the genes on a DNA strand. A typical gene consists of thousands of nucleotides, and a DNA molecule may contain thousands of genes.

Translation is the conversion of the nucleic acid language into the polypeptide (protein) language.  Letters of the polypeptide alphabet are the 20 amino acids common to all organisms. Again, the language is written in a linear sequence, and the sequence of nucleotides of the RNA molecule dictates the sequence of amino acids of the polypeptide.

Transcription   When DNA is transcribed, the result is an RNA molecule. The process is called transcription because the nucleic acid language of DNA has simply been rewritten (transcribed) as a sequence of bases of RNA; the language is still that of nucleic acids. The nucleotide bases of the RNA molecule are complementary to those on the DNA strand. The RNA was synthesized using the DNA as a template.

            Transfer Tool  Transcription and translation are linguistic terms.  The real world  of chemistry is more like model replication with a shape transfer tool.  The chemical world deals with shapes and magnetic attraction between molecules shapes, like a key they fit ordon’t fit.

Replication codes

 

 

     Most DNA is contained in the Nucleus              Synthesis of mRNA  to cytoplasm   to synthesis of Protein

Organelles as chloroplasts and mitochondrion also contain DNA.  Each human mitochondrion  contains about 15,000 nucleotides of DNA, encoding 37 genes. Compared with that of nuclear DNA, which contains some 3 billion nucleotides encoding perhaps 35,000 genes.  Original genetic material was RNA.

 

  

(a)  Transcription of a gene                                (b) ribosome

Transcription. . (a) The transcription of an entire gene occurs in three phases: initiation, elongation, and termination of the RNA. The section of DNA  where the RNA polymerase starts is called the promoter; the place where it stops is called the terminator.  (b) The ribosome. (ba) A simplified diagram of a ribosome, showing its two subunits and sites where mRNA and tRNA molecules bind. (bb) When functioning in polypeptide synthesis, a ribosome holds one molecule of mRNA and two molecules of tRNA. The growing polypeptide is attached to one of the tRNAs.  

Translation: The Players

Messenger RNA (mRNA) The first ingredient required for translation is the mRNA produced by DNA transcription. To translate mRNA requires enzymes and sources of chemical energy, such as ATP plus ribosomes (below) and tRNA.

Transfer RNA (tRNA) to convert the three-letter words ( codons ) to the one-letter, amino acid words of proteins requires an interpreter tRNA

 

(a) A close-up view of transcription                                                              (b) molecule of mRNA

(b) As ANA nucleotides base-pair one by one with DNA bases on one DNA strand (called the template strand), the enzyme RNA polymerase links the DNA nucleotides into an RNA chain. The orange shape in the background is the RNA polymerase

 (right)  A molecule of mRNA. The pink ends are nucleotides that are not part of the message; that is, they are not translated. These nucleotides, along with the cap and tail (yellow),  help the mRNA attach to the ribosome.

The first Genetic Code was probably RNA, not DNA

            In 1981 Thomas Cech and his colleagues discovered that RNA can serve as a biological catalyst. They found that RNA from the protozoan Tetrahymena hermophila can excise 400 nucleotides from its RNA in the absence of any protein.  Other examples of catalytic RNAs have now been discovered in different types of cells. Called ribozymes, these RNA molecules can cut out parts of their own sequences, connect some RNA molecules together, replicate others, and even catalysze the formation of peptide bonds between amino acids. The discovery of ribozymes complements other evidence suggesting that the original genetic material was RNA.

            Ribozymes that were self-replicating probably first arose between 3.5 billion and 4 billion years ago and may have begun the evolution of life on Earth. Early life was an RNA world, with RNA molecules serving both as carriers of genetic information and as catalysts that drove the chemical reactions needed to sustain and perpetuate life. These catalytic RNA’s may have acquired the ability to synthesize protein-based enzymes, which are more efficient catalysts; with enzymes taking over more and more of the catalytic functions, RNA probably became relegated to the role of information storage and transfer. DNA, with its chemical stability and faithful replication, eventually replaced RNA as the primary carrier of genetic information. In modern cells, RNA still plays a vital role in both DNA replication and protein synthesis.

 

 

The gene is the fundamental unit of heredity ;  genes are located on chromosomes

Each species have a characteristic number of chromosomes -- bacterial cells normally possess a single chromosome; human cells possess 46; pigeon cells possess 80. Each chromosome carries a large number of genes.

A gene that specifies a characteristic may exist in several forms, called alleles -- a gene for coat color in cats may exist in alleles that encode either black or orange fur.

The genetic information an organism possesses is its genotype; the trait is its phenotype --  the A blood type is a phenotype; the genetic information that encodes the blood type A antigen is the genotype.  Human height is affected by hundreds of genes as well as environmental factors such as nutrition.

Chromosomes separate through the processes of mitosis and meiosis - Mitosis is the separation of replicated chromosomes during the division of somatic (nonsex) cells. Meiosis is the pairing and separation of replicated chromosomes during the division of sex cells to produce gametes (reproductive cells).

Prokaryoic cells reproduce by simple division

Upper part non-sex cell mitosis, lower part sex cell with mitosis and meiosis

Above are illustrations of the same process by different illustrators

 

left: Male and female gametes (sperm and egg) differ in size  right: The X & Y chromosomes in humans differ in size and genetic content.

 

Same process by two illustrators

Genomic characteristics of bacterium E. coli

Genomic characteristics of humans

 

 

Genetic maps based on rats of recombination           Life is powered by sunlight

Universal tree of life can be constructed from 165 rRNA sequences