Cytogenix (fka CYGX)

[RaptorMan]

I was surprised recently when I posted a link to a Scientific American article, and only one person seemed to take any notice, and it was only a passing notice at that. I thought that since the article cuts right to the heart of what CYGX does, and answers many of the questions that are often posed about the technology, that it would spark some intelligent conversation about the science. Sadly, no one here rose to that opportunity.

For those that may be interested, here are the notes that I put together while studying the article. Understand that these are *notes* that are intended to be studied, and not something that is intended to read like a magazine article. Also, a lot of the definitions given below are not really needed to understand the CYGX technology in layman's terms, but they are required if you want to understand the Scientific American article. I wanted to get down to the most basic levels of the subject matter (i.e. not merely understanding the general idea of what an amino acid is, but rather also understanding what an amino acid is made out of). When you go to that level, you can go from basic chemistry to quantum mechanics in literally 2 or 3 steps. While I found all that stuff fascinating, it's not important to understanding the CYGX technology, so I tried to draw the line at the boundry between biology and nuclear physics.


Definitions
Adenine - A component of nucleic acids, energy-carrying molecules such as ATP, and certain coenzymes that carries hereditary information in DNA and RNA. Chemically, it is a purine base.

ADP - A chemical compound (nucleotide) in living organisms that is formed when another nucleotide (ATP) breaks down to release energy that is used by cells.

Amino Acid - A string of nucleotides that is represented by a codon.

Apoenzyme - The protein component of an enzyme that determines the enzyme’s specific function but has no physiological effect until it becomes attached to another compound (coenzyme).

Archaea - Members of one of two distinct groups of the most primitive living single-celled organisms, similar in size to bacteria but very different in molecular organization.

ATP - A chemical compound (nucleotide) occurring in living organisms that provides most of the energy required by cells during its conversion to another nucleotide (ADP).

Bacterium - A single-celled, often parasitic microorganism without distinct nuclei or organized cell structures. Various species are responsible for decay, fermentation, nitrogen fixation, and many plant and animal diseases. Kingdom: Eubacteria

Carboxyl - A carbon atom and an oxygen atom doubly bonded to each other.

Cell - The smallest independently functioning unit in the structure of an organism, usually consisting of one or more nuclei surrounded by cytoplasm and enclosed by a membrane.

Chromosome - A rod-shaped structure in a cell nucleus carrying the genes that determine sex and the characteristics an organism inherits from its parents.

Codon - A three-letter “word” that specifies one of 20 amino acids or a “stop translating” sign, and which constitutes a set of instructions for the manufacture of a protein. Each letter represents one of the 4 nucleotides, meaning that there are 64 (4x4x4) possible codons, but only 20 having meaning. The remaining codons are redundant, with some amino acids being specified by as many as 6 different codons.

Coenzymes - A nonprotein compound or molecule that combines with a protein (apoenzyme) to form an active enzyme.

Cytoplasm - The complex of chemical compounds and structures within a plant or animal cell excluding the nucleus.

Cytosine - A component of nucleic acids that pairs with guanine to carry hereditary information in DNA and RNA in cells. Chemically, it is a pyrimidine base.

Deoxyribose - A five-carbon simple sugar that is a structural component of DNA.

DNA - Deoxyribonucleic acid. A nucleic acid molecule in the form of a twisted double strand (double helix) that is the major component of chromosomes and carries genetic information.

Enzyme - A complex protein produced by living cells that promotes a specific biochemical reaction by acting as a catalyst.

Eukaryotes - Any organism with one or more cells that have visible nuclei and organelles.

Gene - A sequence of nucleotides that describes a single protein.

Gene Sequence - A “sentence” describing a protein. Codons are the basic units of a gene sequence.

Guanine - A component of nucleic acids that pairs with cytosine to carry hereditary information in DNA and RNA in cells. Chemically, it is a purine derivative.

Hydrophilic - Dissolving in, absorbing, or mixing easily with water. An affinity for water.

Hydrophobic - Not dissolving in, absorbing, or mixing easily with water. An aversion to water.

Mitochondion - A small round or rod-shaped body that is found in the cytoplasm of most cells and produces enzymes for the metabolic conversion of food to energy.

mRNA - Messenger RNA. Carries the genetic instructions out of the cell nucleus into the cytoplasm to be translated.

Nucleic Acid - A biochemical molecule. Any of various high-molecular-weight acids, for example, DNA and RNA, consisting of nucleotide chains that convey genetic information and are found in all living cells and viruses.

Nucleoside - A type of organic compound, found especially in DNA and RNA in living organisms, consisting of a purine or pyrimidine base linked to a sugar, particularly ribose or deoxyribose.

Nucleotide - A type of chemical compound occurring most notably in nucleic acids such as RNA and DNA, consisting of a nucleoside linked to a phosphate group. These form the rungs in the double helix structure of DNA. Each rung consists of two nucleotides—one from each helix—that is known as a base pair. The 4 nucleotide types are:

Adenine (A)
Cytosine (C)
Guanine (G)
Thymine (T) – Replaced by Uracil (U) in RNA

Nucleus - The central body, usually spherical, within a eukaryotic cell, which is a membrane-encased mass of protoplasm containing the chromosomes and other genetic information necessary to control cell growth and reproduction.

Organelles - A specialized part of a cell, for example, the nucleus or the mitochondrion, that has its own particular function.

Peptide - A chemical compound whose amino acids have chemical bonds between carboxyl and amino groups.

Phosphate - One phosphorus atom and 4 oxygen atoms that act as a single entity in reactions. Phosphorus exists in all living cells, and is an essential element for living organisms, but is never naturally found alone. It is also contained in salt (sodium phosphate).

Protein - A complex natural substance that has a high molecular weight and a globular or fibrous structure composed of amino acids linked by peptide bonds.

Purine - A colorless crystalline solid that can be prepared from uric acid and is the parent compound of several biologically important substances.

Purine Derivative - A biologically significant derivative of purine, especially either of the bases adenine and guanine, which are found in RNA and DNA.

Pyrimidine - A strong smelling, weakly basic crystalline organic compound with a six-sided ring structure that includes two nitrogen atoms.

Pyrimidine Derivative - A biologically significant derivative of pyrimidine, especially the bases cytosine, thymine, and uracil found in RNA and DNA.

Riboflavin - An orange-yellow crystalline pigment in the vitamin B complex, essential for normal growth in humans and an important component of many of the body’s enzymes. Also called vitamin B2, lactoflavin, and vitamin G.

Ribonucleotide - A nucleotide that contains the sugar ribose and makes up many important cellular molecules including RNA and energy coenzymes such as ATP.

Ribose - A five-carbon sugar found in all living cells as a constituent of RNA and many other metabolically important compounds, including ribonucleotides, nucleic acids, and riboflavin.

Ribosome - A submicroscopic cluster of proteins and RNA, occurring in great numbers in the cytoplasm of living cells, that takes part in the manufacture of proteins.

RNA - Ribonucleic acid. A nucleic acid that contains the sugar ribose, is found in all living cells, and is essential for the manufacture of proteins according to the instructions carried by genes.

Synonymous Codons - Codons that spell out the same amino acid and generally differ by one letter. Some codons for Leucine and Arginine differ by two letters.

Thymine - A component of nucleic acid that pairs with adenine to carry hereditary information in DNA in cells. Chemically, it is a pyrimidine derivative.

tRNA - Transfer RNA. Catch free-floating amino acids and deliver them to the ribosome.

Uracil - A component of RNA that carries hereditary information in cells. Chemically, it is a pyrimidine derivative. Takes the place of thymine in RNA.


General Information
James D. Watson and Francis H. Crick discovered the shape of the DNA molecule—a double helix—in 1953.

Francis S. Collins was the Human Genome Project leader.

DNA and RNA are both biochemical molecules, while proteins are a different type of molecule.

The arrangement of codons and their corresponding amino acid meanings was once thought to be random, but it now appears that natural selection has chosen and maintained the order for a specific purpose.

Because thymine is replaced by uracil in RNA, any codon containing the letter “T” is a DNA codon, and any codon containing the letter “U” is an RNA codon.

There are approximately 3 billion DNA nucleotide pairs in a human being.

With only 4 types of nucleotide, the information in the double helix must be decoded to tell cells which of 20 amino acids to string together to constitute the thousands of proteins that make up billions of life-forms.

There are 64 possible codons, and only 20 amino acids, which means that 44 codons are redundant. This redundancy provides alternative ways for genes to spell out most proteins. Many of these so called redundant codons differ by one letter (they are redundant because they code for the same amino acid, and not because the letter sequence of the codon is the same). Codons with similar affinities for water tend to differ by the last letter, and codons with the same first letter often code for amino acids that are products or precursors of one another. These features are crucial for the survival of all organisms, and may even speed evolution.

Organisms from bacteria to humans employ the exact same coding rules. However, while most living organisms employ the standard genetic code, at least 16 variations assign different meanings to certain codons. For example, while most organisms would read the RNA codon “CUG” as the amino acid leucine, there are species of the fungus Candida that read it as serine.

Mitochondria are the power generators within all kinds of cells. They have their own genomes, and many have developed their own codon assignments. For example, in the mitochondrial genome of baker’s yeast, 4 of the 6 codons that normally encode leucine instead encode threonine.

So the code can evolve. Nature’s standard codon-amino acids assignments have been refined by billions of years of evolution, and they are no accident. In fact, their arrangement does an excellent job of minimizing the impact of accidents.

Several steps are required to convert a gene’s sequence of bases into an amino acid. First, the DNA gene is copied and edited into a transcript made of RNA, which uses similar nucleic acid bases, except that thymine is replaced by uracil. This results in an mRNA version of the gene. The mRNA carries the genetic instructions out of the cell nucleus into the cytoplasm to be translated.

Once the mRNA is in the cytoplasm, a cellular organelle called a ribosome reads the mRNA 3 letters—or one codon—at a time. While the ribosome is reading the mRNA, cellular butlers known as tRNA fetch free-floating amino acids and deliver them to the ribosome to be added in the specified sequence to the growing chain. Each tRNA binds a 3-nucleotide codon at one end, and a single amino acid at the other end.

As the protein forms it folds into a 3-dimensional form dictated mostly by the amino acids’ affinity for water. Those acids that are hydrophobic tend to fold toward the inside of the protein, and those that are hydrophilic, such as glutamate, face the cell’s watery cytoplasm. An error that replaces a hydrophilic amino acid with a hydrophobic one can drastically alter a protein’s shape or function.

Every coding system has the potential for errors, but some errors are more damaging than others. For example, in English, vowels and consonants are very different, so replacing the letter “s” with the letter “a” makea aentencea leaa readable. By contrast, if “s” is replaced with “z”, which haz a zimilar zound, the phraze iz ztill eazy to underztand.

A good coding strategy is one that reduces the effect of the inevitable occasional error, and indeed, the nucleotide coding of amino acids achieves this goal. Codons sharing 2 of 3 nucleotides usually specify amino acids that are similar in the extent to which they attract or repel water—a property critical to the ultimate functioning of the protein. Because the shape of the protein is dictated by the hydrophobicity of the constituent amino acids, replacing one amino acid with another possessing a similar affinity for water results in an alternation that is relatively harmless in the final protein.

Errors in the transcription of mRNA into an amino acid occur most frequently at the third position of the codon, which is where the binding affinity between mRNA and tRNA is the weakest. Synonymous codons—those coding for the same amino acid—usually differ by only the last letter, so errors of this type often yield the same amino acid meaning.

Minor alterations are statistically more likely to be beneficial than extreme alterations. By minimizing the effects of any mutation, the code maximizes the likelihood that a gene mutation will lead to an improvement in the resulting protein.


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Sources

Freeland, Steven J. and Hurst, Laurence D., 2004. Evolution Encoded.
Scientific American April, 2004: 84-91

Encarta Encyclopedia

Wikipedia
http://en.wikipedia.org/wiki/Main_Page