MOLECULAR & CELLULAR NEUROBIOLOGY 
Master Course Cognitive Neuroscience - Radboud University, Nijmegen

 

INDEX

 INTRODUCTION CELLS AND WITHIN CELLS IN A NUTSHELL GENOMICS MOLECULAR BIOLOGICAL RESEARCH METHODOLOGY NEURODEVELOPMENT  
 

Chapter 2:  Cells and within cells
 

Cells

 DNA and genes

Translation

Receptor Mechanisms
 

    Neurons

    More on DNA

   Proteins, Protein Structure and Protein Analysis

    Ion channel receptors

 

    Glia

   Epigenetics

   Protein folding in the cell

    Tyrosine kinase receptors

Within cells

   Transcription

   Post-translational modifications of proteins

   G-protein-coupled receptors
   Amino ac, Carbohydr, Lipids and Nucleic ac

   Noncoding RNAs

   Protein degradation in the cell - Autophagy

    G-proteins

   Membranes and Membrane Proteins

   miRNAs and the brain

   Protein secretion / Secretory pathway

    Transcription and signalling

   The Exctracellular Matrix

        Transcription factor receptors
 

DNA and genes

The following contains an extension of what was already mentioned in the Introduction. A genome is all the genetic material contained in an organism, including its chromosomes, genes and DNA (deoxyribonucleic acid). Genes carry information for making all the proteins needed by an organism to function. These proteins determine, among other things, an organism's appearance, health, and sometimes behaviour. DNA is made up of four chemical bases (represented by A, T, C, and G) that may be repeated millions of times throughout a genome. The human genome, for example, has 3.2 billion pairs of chemical letters, called bases. The genome is located right in the heart of the cells, in the nucleus. With a few exceptions, each one of the body's trillions of cells contains a complete copy of the genome. These letters follow one another in an order that is specific and unique to form the DNA. This DNA is a complex molecule that looks like a long ladder twisted into a double helix shape. The genes, parts of the DNA, are the functional units of the genome and are located along thread-like structures called chromosomes. Chromosomes are found in the nucleus of the cell, and consist of DNA and proteins. One chromosome may contain thousands of genes. Humans have ~21,000 genes, which carry information to make proteins that determine many traits. Traits are characteristics that are passed on from parents, including things like hair colour and ear shape. We inherit half our genes from our father and half from our mother.

1) Illustration: Chromosomes, genes, and bases

In most animal cells, chromosomes come in pairs, referred to as diploid. But there are many possibilities. For example, some plants are tetraploid (where chromosomes come in fours) and some are octaploid (where chromosomes come in eights). In humans, a cell nucleus contains 23 pairs of chromosomes. For males, 22 of these pairs are of matching chromosomes, and the 23rd pair contains the different X and Y, or sex chromosomes. Females have two X chromosomes in their 23rd pair. Other living things have different numbers of chromosomes. For example, a fruit fly cell has only four pairs of chromosomes, a horse's cell has 32 pairs, and dog's cells have 39 pairs.

3) Photo: Human chromosomes.
Human chromosomes

 

 

Click here for a movie on Explaining DNA structure

Click here for a movie on DNA replication

 

The definition of a gene

A gene is a distinct segment of the DNA that has the appropriate nucleotide sequences promoting transcription to RNA. There are three types of genes:

  1. Protein-coding genes (~21,000): these are transcribed into RNA and then translated into proteins.

  2. RNA-specifying genes (~18,400): these are only transcribed into RNA (8,800 genes encoding small RNAs; 9,600 genes encoding long (>200 bases) noncoding RNAs).

  3. Regulatory genes: according to a narrow definition, these include only untranscribed sequences.

The first two types are also called 'structural genes'.

Typically, we think of a protein-coding gene as having a 5′ end, which is not transcribed but is recognized by proteins that initiate the transcription process, followed by the protein-coding sequence and the 3′ ends for stability. The coding sequence is referred to as the reading frame that starts with an ATG triplet, followed by various arrangements of triplet bases (codons), which specify the amino acids to form a polypeptide. The 3′ end of the gene is not translated into protein but is transcribed to impart stability to the messenger RNA. The codons TGA, or TAA or TAG (triplet stop codon), found at the end of the reading frame, terminate the reading frame for amino acids. The protein-coding sequences (exons) for proteins are separated by noncoding sequences (introns), with the latter spliced out during the transcription process and excluded from the mRNA. The exon–intron boundaries have characteristic sequences, beginning with GT and ending with AG. Among the billion of bases of DNA, these sequence characteristics enable computer algorithms to predict which segments of DNA contain genes coding for protein. The gene requires many proteins to initiate and promote transcription (transcription factors) including enhancers and silencers. Transcription is usually initiated about 32 nucleotides upstream from the starting codon of ATG at a sequence referred to as the TATA box. Thus, protein-coding genes have

  • exons whose sequence encodes the polypeptide;

  • introns that will be removed from the RNA (splicing) before it is translated; different mRNAs can arise from a single gene by alternative splicing (see figure below)

  • a transcription start site

  • a promoter

    • the basal or core promoter located within about 40 bp of the start site

    • an "upstream" promoter, which may extend over as many as 200 bp farther upstream

  • enhancers

  • silencers

Adjacent genes (RNA-coding as well as protein-coding) are often separated by an insulator which helps them avoid cross-talk between each other's promoters and enhancers (and/or silencers).

For details, see under "Transcription" and "Translation".  

 

As mentioned, the latest estimates are that the human genome contains ~21,000 protein-coding genes:

  • Some of these are expressed in all cells all the time. These so-called housekeeping genes are responsible for the routine metabolic functions (e.g. respiration) common to all cells.

  • Some are expressed as a cell enters a particular pathway of differentiation.

  • Some are expressed all the time in only those cells that have differentiated in a particular way. For example, a plasma cell expresses continuously the genes for the antibody it synthesizes.

  • Some are expressed only as conditions around and in the cell change. For example, the arrival of a hormone may turn on (or off) certain genes in that cell.

Although each cell contains a full set of DNA, individual cells use genes selectively. Some genes are used for common internal functions within many types of cells. Some genes are involved in embryonic development, and then are never used again. Some genes help define the character of specific cells, differentiating a brain cell from a liver cell, for example. Other genes may be inactive most of the time. A normal cell activates just the genes it needs at the moment and actively suppresses the rest. How does the information contained in genes get turned into proteins?In other words, how is gene expression regulated? There are several methods used by eukaryotes. Altering the rate of transcription of the gene is the most important and widely-used strategy. However, eukaryotes supplement transcriptional regulation with several other methods:

  • Altering the rate at which RNA transcripts are processed while still within the nucleus.

  • Altering the stability of mRNA molecules; that is, the rate at which they are degraded.

  • Altering the efficiency at which the ribosomes translate the mRNA into a polypeptide.

 

  

 

Alternative splicing: from one pre-mRNA to a number of mRNAs translated to proteins A, B and C

 

 History of DNA - The Pioneers   

 
1886 The Father of Modern Genetics. Gregor Johann Mendel pioneering experiments in hybridization led him to conclude that discrete "factors", now called genes, are responsible for the passing of characteristics to the offspring. In 1866, based on the results of his investigation of the inheritance of "factors" in pea plants, Mendel formulated the first and second laws of heredity.
1953 The Double Helix.  With the help of chemist Rosalind Franklin's outstanding images of DNA X-ray diffraction, James Watson, an American geneticist and biophysicist and Francis Crick, a British biophysicist, demonstrated that the DNA molecule is shaped like a double helix. In recognition of their discovery, Watson and Crick were awarded the Nobel Prize for Medicine in 1962.
Click here for a movie on the Discovery of the double helix (with James Watson).
1961 Messenger RNA Isolated. French biologists François Jacob and Jacques Monod, together with the help of French microbiologist André Lwoff, isolated messenger RNA, the molecule that takes information from DNA in the nucleus to the protein-making machinery in the cytoplasm of the cell. In recognition of their groundbreaking work, Jacob, Monod and Lwoff shared the Nobel Prize for Medicine in 1965.
1972 Genetic Engineering Pioneer. American Biochemist Paul Berg devised a method for cutting DNA molecules in specific places that corresponded to a particular sequence of DNA, or gene. This technique is known as recombinant DNA and is the primary method through which genetic engineering is practiced. For his pioneering work, Paul Berg obtained the 1980 Nobel Prize for Chemistry.
1990-2000 The Genetic Decoder. In October 1990, an international team of scientists officially began the Human Genome Project. Their mission: mapping the entire human genome to show where genes are in relation to one another along the chromosome, and sequencing the entire human DNA by determining the order of As, Cs, Ts and Gs. The first rough map of the entire human genome was completed on June 26, 2000.

Click here for a short movie on the Human genome.  

Next page: More on DNA Go back to:  The Exctracellular Matrix