Thursday, November 12, 2009

Decoding DNA and understanding what makes "Life"

By : Arvind Bhagwath

Future is genetic industry and nanotechnologies which gives new definition on how life is decoded, defined and stored. For me "life" as an energy inside a particular boundary and this energy helps metabolism to take place inside the boundary, metabolism helps to distribute energy and generate information. A "genetic component" carries information/energy to other energy boundary resulting a bi-product being created. This process repeats until the energy levels are transmitted or distributed to maintain the balance.
We all know that "genetic component" is composed of Deoxyribonucleic acid(DNA) which is a molecule composed of two chains that coil around each other to form a double helix carrying genetic instructions for the development, functioning, growth and reproduction of all known organisms and the information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). 
The haploid human genome (23 chromosomes) is estimated to be about 3.2 billion bases long and to contain 20,000–25,000 distinct protein-coding genes. More than 99 percent of those bases are the same in all people.

As shown below, it is now possible to store binary code(Digital data) in DNA string protein sequence and retrieve them back. It is also possible now to decode DNA of any living organism including humans that are basis of life on Planet earth.


DNA Digital Data Storage
To understand origin of Life, we need to understand DNA and study how did it evolve?
A most important property of DNA is that it can replicate, or make copies of itself and when we speak about cell evolution, it is assumed that first cell types were heterotrophic cells which were incapable of producing their own food and then evolved to autotrophs which can produce chemicals to store energy and then came chemoautotroph which can store energy found in certain inorganic chemicals and then came prokaryotes about 2 - 1.5 billion years ago and then finally eukaryotes which had membranes to isolate certain chemical reactions and cellular life then evolved.

Mitosis is the process by which eukaryotic cells replicate by dividing into two genetically identical cells. It is the process by which new cells are formed in the growing embryo and after birth. Mitosis also replaces cells that have died or been shed and stem cells retain the capacity to divide throughout life.

Meiosis is the specialized process by which gametes (sperm and eggs) are produced for sexual reproduction in the ovaries and testes. Humans have 22 pairs of homologous chromosomes and one pair of sex chromosomes; one member of each pair came from the mother, and the other from the father. The 46 chromosomes are referred to as the diploid (2n) number, because there are two of each.
Information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases. base pair (bp) is a unit consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA and RNADictated by specific hydrogen bonding patterns, Watson–Crick base pairs (guaninecytosine and adeninethymine) allow the DNA helix to maintain a regular helical structure that is subtly dependent on its nucleotide sequence.The complementary nature of this based-paired structure provides a redundant copy of the genetic information encoded within each strand of DNA. 
Transcription is the first step of DNA based gene expression, in which a particular segment of DNA is copied into RNA (especially mRNA) by the enzyme RNA polymerase as shown below.
The stretch of DNA transcribed into an RNA molecule is called a transcription unit and encodes at least one gene. If the gene encodes a protein, the transcription produces messenger RNA (mRNA); the mRNA, in turn, serves as a template for the protein's synthesis through translation as shown below. Alternatively, the transcribed gene may encode for non-coding RNA such as microRNAribosomal RNA (rRNA), transfer RNA (tRNA), or enzymatic RNA molecules called ribozymes. Overall, RNA helps synthesize, regulate, and process proteins; it therefore plays a fundamental role in performing functions within a cell.
Below is the genetic code that describes the translation of an RNA codon into one of 20 different amino acids. The first three circles, moving from the inside out, represent the 1st, 2nd, and 3rd nucleotides of a given codon. The 4th, 5th, and 6th circles define the translated amino acid in three ways: the amino acid’s full name, its 3-letter abbreviation, and its single-letter abbreviation. Three of the 64 total RNA codons are stop codons, which halt translation and implicitly add a 21st stop symbol to the amino acid alphabet. 
Proteins are molecules made of amino acids and a gene is a segment of a DNA molecule that contains the instructions needed to make a unique protein. As we know, all of our cells contain the same DNA molecules(adenine (A), guanine (G), cytosine (C), and thymine (T)), but each cell uses a different combination of genes to build the particular proteins it needs to perform its specialized functions.
During translation, the ribosomes read the mRNA sequence of bases 3 at a time. These 3-letter combinations (called codons) each code a particular amino acid and the 4 bases (adenine, thymine, guanine and cytosine) = 64 (43) codons

NOTE : Only 20 amino acids are required to build all of the proteins in our bodies and it is the particular sequence of amino acids that determines the shape and function of the protein.

Below are different types of proteins:

Haemoglobin is a protein that works as transport proteins move oxygen around our body


Haemoglobin is a protein making up 95% of the dry mass of a red blood cells(RBC) to support transporting Oxygen around the body. It is made up of four polypeptide chains and each bound to one haem group. Each Haem group can combine with one oxygen molecule and hence one molecule/cell of haemoglobin can carry four oxygen molecules.
To further add, enzymes are proteins that facilitate biochemical reactions. Example : Pepsin is a digestive enzyme in your stomach that helps to break down proteins in food. Antibodies are proteins produced by the immune system to help remove foreign substances and fight infections.
Proteins like actin and myosin are contractile proteins that are involved in muscle contraction and movement. 

Proteins like collagen and elastin are structural proteins that provide support in our bodies in connecting tissues and finally proteins like insulin controls our blood sugar concentration by regulating the uptake of glucose into cells.


Everything is Protein driven. From Hydrogen Bonds to “Life” and defense mechanism to protect it.
All these functions or rigid extensions or modifications of leaves, stems or buds with sharp/stiff ends generally serve the same function as defense mechanism. It got developed with several million years of evolution based on events recorded in DNA which is just stored in code of four chemical bases adenine (A), guanine (G), cytosine (C), and thymine (T) :-)
Every species is capable of regeneration, from plants to bacteria to humans that is powered by DNA and along certain additional protein generation as defensive function.
Thorns in Roses was a process of defensive regeneration by DNA (mitosis cell division) which is different from reproduction(meiosis). In biology, regeneration is the process of renewal, restoration, and growth that makes organisms to regenerate from events that cause disturbance or damage.
Example : If you cut the leg off a salamander, it will grow back. Similarly in roses, they have thorns to protect them from being eaten by animals. Extra protection functions like Thorns for Roses or Regeneration is triggered by DNA from earlier events of damage.
NOTE : Thorns are derived from shoots and Prickles are derived from epidermistissue.

When we speak about DNA in animal or plant cells, Hydrogen bonding is the chemical mechanism that underlies the base-pairing rules. Hydrogen bonds are weak electrostatic attractions between atoms displaying partial positive and partial negative charges.

The larger nucleobases, adenine and guanine, are members of a class of double-ringed chemical structures called purines; the smaller nucleobases, cytosine and thymine (and uracil), are members of a class of single-ringed chemical structures called pyrimidines. Purines are complementary only with pyrimidines: pyrimidine-pyrimidine pairings are energetically unfavorable because the molecules are too far apart for hydrogen bonding to be established; purine-purine pairings are energetically unfavorable because the molecules are too close, leading to overlap repulsion. Purine-pyrimidine base-pairing of AT or GC or UA (in RNA) results in proper duplex structure. Uracil(U) is substituted for thymine in the RNA strand.

Hydrogen bonds are critically important in biology because they help explain the solubility of molecules in water, the structure of macro molecules (such as DNA and protein), and the formation of stable lipid bi-layer membranes.

When we speak about DNA in animal or plant cells, Hydrogen bonding is the chemical mechanism that underlies the base-pairing rules. Hydrogen bonds are weak electrostatic attractions between atoms displaying partial positive and partial negative charges. The partial positive charges are produced when hydrogen atoms are associated with another atom through a polar covalent bond. The partial negative charges are associated with an atom (e.g., oxygen) that has a higher affinity for electrons.The oxygen atom has two pairs of electrons in its outermost energy level that are not in bonding orbitals. These four electrons form a negatively charged "cloud" of electron density on the side of the water molecule opposite from the hydrogen atoms. The oxygen atom is much more electro-negative than the hydrogen atom, so, when a bonding orbital forms between the oxygen and hydrogen atoms, the electrons in the bonding orbital are disproportionately distributed toward the oxygen side of the polar covalent bond. This results in a partial negative charge (-) associated with the oxygen atom. The full positive charge of the hydrogen nucleus is poorly covered by the thin electron density and "shows through", resulting in a partial positive charge (+).The weak electrostatic attraction between the partial negative and partial positive charges is a hydrogen bond.In molecular biology, two nucleotides on opposite complementary DNA or RNA strands that are connected via hydrogen bonds are called a base pair.

Replication of DNA thus defines life, but when was first life on planet Earth?
The Earth is thought to be approximately 4.6 billion years old, but life is believed to have occurred approximately 3.5 billion years ago. There is a idea that long ago complex collections of chemicals formed the first cells and Life began in the oceans from simple chemicals joining together in a primordial soup. Lightening and ultraviolet radiation from the Sun acted on the atmosphere to form rapid chemical bonds of amino acids. Complex chemicals evolved into living cells from the complex organic molecules that formed on the Earth's surface. 

What normally happens to atoms when they are exited by external light radiation?


It is observed that light from the sun hitting moon dust causes it to become charged through the photoelectric effect. The charged dust then repels itself and lifts off the surface of the Moon by electrostatic levitation.
So let us look this behavior by various elements present in earth.In general, atoms are most stable when all of their orbital are occupied by two electrons unless disturbed by external energy. Isolated atoms, such as hydrogen(H), carbon (C), nitrogen (N) and oxygen (O), have some orbitals that are not occupied by two electrons. For example, hydrogen is an atom that has a single proton (its nucleus) and a single electron. The electron of the hydrogen atom is in a 1s orbital. Different types of atoms (e.g., oxygen and hydrogen) have very different affinities for electrons. This differential affinity for electrons is demonstrated with different bonds or formation of Ions, covalent bond etc.

For instance: Sodium metal has tendency to lose electron for Sun's radiation and the ferric iron in the ocean is ultimate electron acceptor. I have taken Sodium, since we all know that sodium is present in great quantities in the earth's oceans as sodium chloride.

For more details, let us look at Periodic table below:
Most alkali metals have lowest electro negativeness (they tend to lose electrons). Atoms of high electro negativity (upper right nonmetals) tend to gain electrons.The alkali metals, found in group 1 of the periodic table, are highly reactive metals that do not occur freely in nature and these metals have only one electron in their outer shell. Therefore, they are ready to lose that one electron in ionic bonding with other elements. Metalloids have properties of both metals and non-metals. Some of the metalloids, such as silicon and germanium, are semi-conductors which again show there affinity to light radiation. This is proved in semi-conductor technology and when we speak about Noble gases, they have 8 electrons in their outer shell, making them stable. These elements have an oxidation number of 0. This prevents them from forming compounds readily.
The radiation from Sun results in Photoelectric effect on atoms. When an external electromagnetic radiation hits a atom, we see that electrons exhibits force by external radiation and gets exited. The changes in electrons in atoms results chemical reactions to take place by creating/breaking bonds.
All the energy in animals, plants, oil, gas, and coal originally came from the Solar radiation captured through photosynthesis. Photosynthesis is the process by which plants, some bacteria use the energy from sunlight to produce sugar, which cellular respiration converts into ATP, the "fuel" used by all living things. The conversion of unusable sunlight energy into usable chemical energy, is associated with the actions of the green pigment chlorophyll. Most of the time, the photosynthetic process uses water and releases the oxygen that we absolutely must have to stay alive. The Glucose is used as food as well!
The overall reaction of this process as:
6H2O + 6CO2 + Sun Light ----------> C6H12O6+ 6O2











Living things are composed primarily of water and organic compounds, enzymes are protein catalysts that carry out the chemical reactions of metabolism. All chemical reactions require activation energy to break chemical bonds and begin the reaction. In the process of photosynthesis, the phosphorylation of ADP to form ATP using the energy of sunlight is called photophosphorylation. Only two sources of energy are available to living organisms: sunlight and reduction-oxidation (redox) reactions. All organisms produce ATP, which is the universal energy currency of life. In photophosphorylation, light energy is used to create a high-energy electron donor and a lower-energy electron acceptor. Electrons then move spontaneously from donor to acceptor through an electron transport chain.

Phosphorylation of a molecule in general is the attachment of a phosphoryl group and together with its counterpart, dephosphorylation, it is critical for many cellular processes in biology and defines what we call as "life". 

Can the life be created now using all the main components for Life?
Consider a very simplest way to create life using all the main components required for life. For example, preparing a soup of all the dissolved organic components and exposing the soup to sun radiation. When we speak about components, water is the most abundant molecule on Earth's surface, composing of about 70% of the Earth's surface. Water also makes up 75 % of the human body.Modern chemistry explains us how water was formed now or during primitive earth.The structural and electrical properties of the water should be discussed in relation to membrane functions, in particular transport of ions across membranes.Water is primarily a liquid under standard conditions, however, all the elements surrounding oxygen in the periodic table, nitrogen, fluorine, phosphorus, sulfur and chlorine, all combine with hydrogen to produce gases under standard conditions.

The reason that water forms a liquid is that it is more electronegative than all of these elements (other than fluorine). Oxygen attracts electrons much more strongly than hydrogen, resulting in a net positive charge on the hydrogen atoms, and a net negative charge on the oxygen atom. The presence of a charge on each of these atoms gives each water molecule a net dipole moment. Electrical attraction between water molecules due to this dipole pulls individual molecules closer together, making it more difficult to separate the molecules and therefore raising the boiling point. This attraction is known as hydrogen-bonding. And again, some elements show ionic bond when dissolved in water. For instance, when sodium and chlorine atoms are mixed together, the sodium atom gives its electron to the chlorine atom. The sodium and chlorine atoms become the sodium and chloride ions (Na and Cl, respectively). The sodium and chloride ions have opposite electrical charges and so the two ions are electro statically attracted to each other. The electrostatic attraction between two ions, each with a full (not partial) electric charge, is called an ionic-bond.
These electrochemical reactions are very much necessary for transport of ions across membranes.Now create a soup with water and amphiphilic molecules. The amphiphilic molecules forms a oily surface. One end interact with water and one end does not interact with water. These molecules automatically self-assemble to form bi-layers.These are the technique used to make up the walls of our cells and several research and available fossils demonstrates the formation of organic soup during primitive earth.So we can assume that there could be some molecules trapped in-between bi-layer and we have learnt that different molecules behave differently with Sun radiation. Expose the bi-layer with Sun's radiation, some of molecules or elements sensitive to light radiation absorbs the light and becomes excited resulting in formation of bonds and chemical reaction results in action or we can call them as metabolism. Appropriate geometrical correspondence of hydrogen bond donors and acceptors allows only the "right" pairs to form stably.

If we go still deeper, we see that RNA or DNA replication are environmentally forced. In recent research it is seen that solar rays/Cosmic rays and cycles (day and night) could have forced the replication process triggering in growth as shown above. RNA or DNA strands that we currently have in cells are due to a large number of variations that led into forming pair.4-billion-year of evolution has resulted forming from a basic pair to 3000000000 DNA nucleotide pairs that we currently have in human. We still see same less pairs in bacteria (about 400000 DNA nucleotide pairs).

Summary : 99% of the mass of the human body is made up of the six main elements : oxygen, carbon, hydrogen, nitrogen, calcium along with other elements that are phosphorus, Potassium, Sulfur, Chlorine, Sodium, Magnesium, Iron, Cobalt, Copper, Zinc, Iodine, Selenium, Fluorine. 

Different types of atoms have very different affinities for electrons and radiation from Sun. If we take a look of elements in living organisms, we see it is these elements present in our body in which some are either electron donors and some are electron acceptors. Each time when the atoms are exited by external source results in partial charges created by giving the electrons or by accepting the electrons and we have partial positive and partial negative charges. Hence atoms interact with other partial positive and partial negative charges associated with other molecules that result in creation of bonds and these bonds lead formation of Organic molecules. Electrical asymmetries in these molecules would have resulted in further creation of complements or living cells and then again some of molecules in these living cells absorbs the external radiation and will try to stay in stable state by transferring the energy to do something useful. Can we now call this balance of charges or electrical asymmetries as metabolism what we know as "life".

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