Wednesday, 4 March 2015

DNA, RNA and proteins: The three essential macromolecules of life

 

From Wikipedia, the free encyclopedia

All living organisms are dependent on three types of very large molecules for essentially all of their biological functions. These molecules are DNA, RNA and proteins, and are classified as biological macromolecules.[1] Without DNA, RNA and proteins, no known forms of life could exist. This is because each molecule plays an indispensable role in biology.[2] The simple summary is that DNA makes RNA, and then RNA makes proteins.

DNA is an informational macromolecule that encodes the complete set of instructions (the genome) that are required to assemble, maintain, and reproduce every living organism.[3]

Proteins are responsible for catalyzing the myriad biochemical reactions that are required to provide food and energy for every organism, and for all forms of movement. In addition proteins carry out all of the other functions of any given organism, for example photosynthesis, or, for example in animals, neural function, vision, and structure (skin, tendons, exoskeleton, etc.).[4]

RNA is multifunctional, its primary responsibility is to make proteins, according to the instructions encoded within a cell’s DNA. They control and regulate many aspects of protein synthesis in eukaryotes.

 

Contents

Comparison of DNA, RNA and proteins

image

Common structural features of DNA, RNA and proteins

While many typical cellular molecules (for example sugars and fats) contain tens, or rarely hundreds, DNA, RNA and proteins are typically composed of thousands of atoms (millions for most DNA molecules).

DNA, RNA and proteins are all polymers, long molecules that consist of a repeating structure of related building blocks (also termed monomers; nucleotides in the case of DNA and RNA, amino acids in the case of proteins). In general, DNA, RNA and proteins are all unbranched polymers, and so can be represented in the form of a string. Indeed, they can be viewed as a string of beads, with each bead representing a single nucleotide or amino acid monomer linked together through covalent chemical bonds into a very long chain.

In most cases, the monomers within the chain have a strong propensity to interact with other amino acids or nucleotides. In DNA and RNA, this can take the form of Watson-Crick base pairs (G-C and A-T or A-U), although many more complicated interactions can and do occur.

Divergent structural features

Because of the double-stranded nature of DNA, essentially all of the nucleotides take the form of Watson-Crick pairs between nucleotides on the two complementary strands of the double helix.

In contrast, both RNA and proteins are normally single-stranded. Therefore, they are not constrained by the regular geometry of the DNA double helix, and can and do fold into a vast number of complex three-dimensional shapes. These different shapes are responsible for many of the common properties of RNA and proteins, including the formation of specific binding pockets, and the ability to catalyze biochemical reactions.

 

Why DNA is best for encoding genetic information

DNA and RNA are both capable of encoding genetic information, because there are biochemical mechanisms which read the information coded within a DNA or RNA sequence and use it to generate a specified protein. On the other hand, the sequence information of a protein molecule is not used by cells to functionally encode genetic information.

DNA has three primary attributes that allow it to be far better than RNA at encoding genetic information. First, it is normally double-stranded, so that there are a minimum of two copies of the information encoding each gene in every cell. Second, DNA has a much greater stability against breakdown than does RNA, an attribute primarily associated with the absence of the 2'-hydroxyl group within every nucleotide of DNA. Third, highly sophisticated DNA surveillance and repair systems are present which monitor damage to the DNA and repair the sequence when necessary. Analogous systems have not evolved for repairing damaged RNA molecules.

 

Why proteins are best for catalyzing biological reactions

The single-stranded nature of protein molecules, together with their composition of 20 or more different amino acid building blocks, allows them to fold in to a vast number of different three-dimensional shapes, while providing binding pockets through which they can specifically interact with all manner of molecules. In addition, the chemical diversity of the different amino acids, together with different chemical environments afforded by local 3D structure, enables many proteins to act as enzymes, catalyzing a wide range of specific biochemical transformations within cells. In addition, proteins have evolved the ability to bind a wide range of cofactors and coenzymes, smaller molecules that can endow the protein with specific activities beyond those associated with the polypeptide chain alone.

 

Why RNA is multifunctional

RNA encodes genetic information that can be translated into the amino acid sequence of proteins, as evidenced by the messenger RNA molecules present within every cell, and the RNA genomes of a large number of viruses. The single-stranded nature of RNA, together with tendency for rapid breakdown and a lack of repair systems means that RNA is not so well suited for the long-term storage of genetic information as is DNA.

In addition, RNA is a single-stranded polymer that can, like proteins, fold into a very large number of three-dimensional structures. Some of these structures provide binding sites for other molecules and chemically-active centers that can catalyze specific chemical reactions on those bound molecules. The limited number of different building blocks of RNA (4 nucleotides vs >20 amino acids in proteins), together with their lack of chemical diversity, results in catalytic RNA (ribozymes) being generally less-effective catalysts than proteins for most biological reactions.

 

References

  • Berg, Jeremy Mark; Tymoczko, John L.; Stryer, Lubert (2010). Biochemistry, 7th ed. (Biochemistry (Berg)). W.H. Freeman & Company. ISBN 1-4292-2936-5. Fifth edition available online through the NCBI Bookshelf: link
  • Walter, Peter; Alberts, Bruce; Johnson, Alexander S.; Lewis, Julian; Raff, Martin C.; Roberts, Keith (2008). Molecular Biology of the Cell (5th edition, Extended version). New York: Garland Science. ISBN 0-8153-4111-3.. Fourth edition is available online through the NCBI Bookshelf: link
  • Golnick, Larry; Wheelis, Mark. The Cartoon Guide to Genetics. Collins Reference. ISBN 978-0-06-273099-2.
  • Takemura, Masaharu (2009). The Manga Guide to Molecular Biology. No Starch Press. ISBN 978-1-59327-202-9.
  • http://en.wikipedia.org/wiki/DNA,_RNA_and_proteins:_The_three_essential_macromolecules_of_life

    Why thymine instead of uracil?

     

    by Piter Kehoma Boll | September 29, 2012 · 12:05 pm

    About a year ago, while I was in my class of Techniques of Molecular Diagnosis, an interesting doubt sprouted: why does DNA use thymine instead of uracil as RNA does?

    I hope everybody reading this knows about nucleic acids and the difference between DNA and RNA. As a very quick review:

    RNA (ribonucleic acid) is a polymer made of ribonucleotides, compound molecules made of three parts, or smaller molecules: a nitrogenous base (adenine, uracil, cytosine or guanine), a ribose sugar and a phosphate group.

    DNA (deoxyribonucleic acid) is similar, but instead of uracil it has thymine, and instead of a ribose sugar is has a deoxyribose, so that it is made of deoxyribonucleotides. Another difference is that DNA is a double chain twisted helicoidally, where two nitrogenous bases (each from one of the chains) are connected. Adenine is always connected to thymine and cytosine always to guanine, so that one chain is always dependent on the other.

    Currently it’s highly accepted that RNA was the first nucleic acid to exist and that DNA evolved from it, so the changes in the sugar and one of the nitrogenous bases must have some advantage.

    To understand that, let’s take a look at the structure of the uracil:

    Uracil

    The only difference between it and thymine is the presence of a methyl group at the last one:

    Thymine

    In fact, thymine is also called 5-methyluracil. But let’s go to the explanation:

    While nucleotides are synthesized, the nucleotide-monophosphates (NMPs), i.e., the set nitrogenous base + sugar + phosphate is dehydroxylated, creating 2’-deoxy-nucleotide-monophosphate (dNMPs), i.e., GMP, AMP, CMP and UMP (for guanine, adenine, cytosine and uracil) are changed to dGMP, dAMP, dCMP and dUMP.

    This modification by dehydroxylation has been shown to make the phosphodiester bonds (the bonds of phosphates on the sugar) less susceptible to hydrolysis and damage by UV radiation. It assures that a DNA molecule will not be as easy to be broken as an RNA molecule, which is very useful since DNA carries all the information to build up the organism.

    After the dehydroxilation of the nucleotide-monophosphates, the next step, catalyzed by folic acid, add a methyl group to the uracil to form a thymine, so turning dUMP into dTMP.

    There are many explanations for that:

    1. Despite uracil’s tendency to pair with adenine, it can also pair with any other base, including itself. By adding a methyl group (which is hydrophobic) and turning it into thymine, its position is reorganized in the double-helix, not allowing those wrong pairings to happen.

    2. Cytosine can deaminate to produce uracil. You can see in the picture below that the only difference between them is the change from an O in uracil to an NH2 in cytosine. The problem is that, if uracil were a component of DNA, the repair systems would not be able to distinguish original uracil from uracil originated by deamination of cytosine. So using thymine instead makes it way easier and more stable, as any uracil inside DNA must come from a cytosine and so it can be replaced by a new cytosine.

    Cytosine

    This didn’t evolve for that purpose, of course. Evolution cannot predict what happens. Probably during the earliest times of life, eventually an error changed uracil for thymine and it was found to be more stable to carry information, since such a molecule wouldn’t be destroyed so easily and thus would succeed in passing its “layout” to the next generation.

    It makes me wonder… Could some alien life form have found an alternative way to deal with RNA’s (or something equivalent) instability?

    – – –

    Main Reference:

    Jonsson, J. (1996). The Evolutionary Transition from Uracil to Thymine Balances the Genetic Code Journal of Chemometrics, 10, 163-170 DOI: 10.1002/(SICI)1099-128X(199603)10:2

    https://earthlingnature.wordpress.com/2012/09/29/why-thymine-instead-of-uracil/

    DNA, genes and chromosomes

     

    Illustration of a double helix

    Your genes are part of what makes you the person you are. You are different from everyone alive now and everyone who has ever lived.

     

    DNA

    But your genes also mean that you probably look a bit like other members of your family. For example, have you been told that you have 'your mother's eyes' or 'your grandmother's nose'?

    Genes influence what we look like on the outside and how we work on the inside. They contain the information our bodies need to make chemicals called proteins. Proteins form the structure of our bodies, as well playing an important role in the processes that keep us alive.

    Genes are made of a chemical called DNA, which is short for 'deoxyribonucleic acid'. The DNA molecule is a double helix: that is, two long, thin strands twisted around each other like a spiral staircase.

    27 DNA.gif

    The DNA double helix showing base pairs

    The sides are sugar and phosphate molecules. The rungs are pairs of chemicals called 'nitrogenous bases', or 'bases' for short.

    There are four types of base: adenine (A), thymine (T), guanine (G) and cytosine (C). These bases link in a very specific way: A always pairs with T, and C always pairs with G.
    The DNA molecule has two important properties.

    • It can make copies of itself. If you pull the two strands apart, each can be used to make the other one (and a new DNA molecule).
    • It can carry information. The order of the bases along a strand is a code - a code for making proteins.

    Genes

    A gene is a length of DNA that codes for a specific protein. So, for example, one gene will code for the protein insulin, which is important role in helping your body to control the amount of sugar in your blood.

    Genes are the basic unit of genetics. Human beings have 20,000 to 25,000 genes. These genes account for only about 3 per cent of our DNA. The function of the remaining 97 per cent is still not clear, although scientists think it may have something to do with controlling the genes.

    Chromosomes

    If you took the DNA from all the cells in your body and lined it up, end to end, it would form a strand 6000 million miles long (but very, very thin)! To store this important material, DNA molecules are tightly packed around proteins called histones to make structures called chromosomes.

    105-Gene-unwrapped.gif

    The packaging of DNA into chromosomes

    Human beings have 23 pairs of chromosomes in every cell, which makes 46 chromosomes in total. A photograph of a person's chromosomes, arranged according to size, is called a karyotype.

    The sex chromosomes determine whether you are a boy (XY) or a girl (XX). The other chromosomes are called autosomes.

    106-autosomes.gif

    The karyotype of a male human being

    The largest chromosome, chromosome 1, contains about 8000 genes. The smallest chromosome, chromosome 21, contains about 300 genes. (Chromosome 22 should be the smallest, but the scientists made a mistake when they first numbered them!).

    The DNA that contains your genes is stored in your cells in a structure called the nucleus.

    107-nucleus.gif

    A diagram of animal cell showing the nucleus

    Topic related resources

    Back to top

    Creative commons logo

    This work is licensed under a Creative Commons Licence.

    http://www2.le.ac.uk/departments/genetics/vgec/highereducation/topics/dnageneschromosomes

    NASA Rebuilds 3 Building Blocks of Life, What Next?

    Left to right: Ames scientists Michel Nuevo, Christopher Materese and Scott Sandford reproduce uracil, cytosine, and thymine, three key components of our hereditary material, in the laboratory.<br />Image Credit: NASA/ Dominic Hart

    Left to right: Ames scientists Michel Nuevo, Christopher Materese and Scott Sandford reproduce uracil, cytosine, and thymine, three key components of our hereditary material, in the laboratory. Image Credit: NASA/ Dominic Hart

     

    in SCIENCE March 4, 2015

    Now that NASA scientists have reproduced uracil, cytosine, and thymine, three key components of our hereditary material, in the laboratory, the question is how would it help the mankind or replicate the mankind in outer space.

    NASA said its scientists discovered that an ice sample containing pyrimidine exposed to ultraviolet radiation under space-like conditions was able to produce the three essential ingredients of life.

    Nucleobases structures

    Pyrimidine is a ring-shaped molecule made up of carbon and nitrogen and is the central structure for uracil, cytosine, and thymine, which are found in RNA and DNA. Image Credit: NASA

    Nucleobases cytosine thymine image

    The ring-shaped molecule pyrimidine is found in cytosine and thymine. Image Credit: NASA

    Pyrimidine molecule is made up of carbon and nitrogen and is the central structure for uracil, cytosine, and thymine, which together form the genetic code found in ribonucleic (RNA) and deoxyribonucleic acids (DNA). RNA and DNA are key to protein synthesis, besides other uses.

    “We have demonstrated for the first time that we can make uracil, cytosine, and thymine, all three components of RNA and DNA, non-biologically in a laboratory under conditions found in space,” said Michel Nuevo of NASA’s Ames Research Center in California.

    “We are showing that these laboratory processes, which simulate conditions in outer space, can make several fundamental building blocks used by living organisms on Earth,” said Dr. Nuevo.

    Nobody really understands how life began on Earth but now these scientists say their experiments suggest that once the Earth formed, many of the building blocks of life were likely present from the beginning. “Since we are simulating universal astrophysical conditions, the same is likely wherever planets are formed,” says Scott Sandford, a space scientist at Ames, which means replication of life in outer space is the next step that NASA may undertake.

    The research was funded by the NASA Astrobiology Institute (NAI) and the NASA Origins of Solar Systems Program.

    http://www.microfinancemonitor.com/2015/03/04/nasa-rebuilds-3-building-blocks-of-life-what-next/