DNA: The Molecule That Defines Us

DNA: The Molecule That Defines Us

You, your parents, and your siblings have similar traits. But why do you still not closely resemble each other? The answer lies in a tiny, but long molecule that is unique to every living organism (except for identical twins)* on this planet: DNA, or deoxyribonucleic acid. DNA serves as a template for the production of proteins, affecting our traits and carrying out functions in the body. 

The Nucleotide

      DNA consists of repeating subunits called nucleotides. A nucleotide consists of a pentose (five carbon) sugar, phosphate group, and a nitrogenous base. The sugar is known as deoxyribose, and it forms a covalent bond with the phosphate group. This covalent bond is called a phosphodiester linkage. The repeating bonds between deoxyribose and the phosphate group form the sugar-phosphate backbone of DNA. A hydrogen bond joins the nitrogenous base pairs. This hydrogen bond is weak so that it can easily be broken for DNA replication.  

                                                                                  

Figure 2: Structure of DNA

                                                                                         

Nitrogenous Base Pairs 

DNA consists of four base pairs: adenine, thymine, cytosine, and guanine. As mentioned earlier, a hydrogen bond links them. Adenine binds with thymine, and cytosine binds with guanine. Adenine and guanine are known as purines, and they contain two rings in their structure. Cytosine and thymine are known as pyrimidines, and they contain one ring in their structure. This is why adenine, a purine, is able to form a bond with thymine, a pyrimidine, and not with guanine. These base pairs can also be found in other molecules throughout the body. For example, ATP (adenosine triphosphate), the main energy molecule of the body, consists of adenine and three phosphate groups. GTP (guanosine triphosphate) consists of guanine and three phosphate groups and plays a major role in protein synthesis and signal transduction in a cell. 

Why must DNA replicate?

DNA replication is important for cell division. Each daughter cell must have the same DNA as the parent cell. Cells divide for growth, repair and reproduction. For example, epidermal cells must divide to replace the damaged cells at a wound. DNA replication is semi-conservative, which means that each new DNA double helix formed after replication has one parent strand (which was used as the template) and one new strand. Before we dive into the process of DNA replication, it is important to be familiar with some physical properties of DNA. DNA is antiparallel, which means that the two DNA strands in a double helix are oriented in opposite directions. Each strand has a 5'end and a 3'end. In the diagram below, notice how the 5' ends of both strands are located on different sides.

Figure 3: DNA is antiparallel

The 5' and 3' ends can be distinguished by the functional groups attached to the pentose sugar; if a phosphate group is hanging from the uppermost deoxyribose, it is the 5' end. If a hydroxyl group is hanging from the deoxyribose, it is the 3' end.

DNA/Gene Expression

Surprisingly, only about 1% of the genome codes for proteins! Expression of certain genes in every cell is not required, and there are many mechanisms that either enhance or inhibit gene expression in cells. 

 A gene is a portion of DNA that codes for a certain trait. All cells in the body have the same genes, but they each have different genes turned on in order to perform their specialized functions. The MCR1 gene, which produces melanin, is present in all cells, but is only expressed in melanocytes. Histones are proteins that pack DNA into a tight, orderly form, allowing it to fit into the cell's microscopic nucleus. In histone acetylation, acetyl groups are added to histone proteins, which loosens the chromatin and makes DNA available for protein synthesis. This enhances gene expression. On the other hand, histone methylation adds methyl groups to histones, which makes the chromatin more tightly packed, inhibiting transcription. If genes are not transcribed, they will not be expressed. 

Another way in which gene expression is controlled is through repressors.  Once activated, a repressor binds to a segment of DNA and prevents it from being transcribed, thus inhibiting gene expression. 

Transcription factors also enhance gene expression. If inactivated, transcription will not occur, limiting gene expression.

DNA vs RNA 

What makes DNA different from RNA? RNA, ribonucleic acid, is another type of hereditary material that is much shorter than DNA. Viruses that cause the flu, common cold, measles, AIDS, and rabies use RNA as their genetic material. Although similar to DNA, RNA's structure is slightly different. RNA is single stranded, contains the sugar ribose instead of deoxyribose, and consists of the base uracil instead of thymine. Moreover, RNA functions as an intermediary between DNA and a protein.

Figure 4: RNA vs DNA

DNA Influences the Type of Protein Produced 

In protein synthesis, DNA serves as a template for mRNA, and mRNA serves as a template for the sequence of amino acids in a protein. The three types of RNA are mRNA (messenger RNA), tRNA (transfer RNA), and rRNA (ribosomal RNA). First, DNA is transcribed into its complementary mRNA bases (recall that A and U are complementary and G and C are complementary) in a process called transcription, which occurs in the nucleus. Each triplet of mRNA bases is known as a codon. A codon codes for an amino acid (repeating subunit of a protein). 

After transcription, the mRNA sequence undergoes modifications because only some segments of the mRNA, known as exons, contain the code necessary for to produce a protein. The non-coding regions, known as introns, are spliced out. But first, the newly formed mRNA sequence is capped at both ends since it is weak and can easily degrade. A GTP molecule is added to the 5' end, forming a 5' cap, and adenosine nucleotides are added to the 3' end, forming a poly-A tail. Then, the introns are removed from the mRNA sequence and the exons are joined together. It is possible for the exons to be joined in any order, resulting in different versions of a protein. This phenomenon is called alternative RNA splicing.Thus, one gene can code a variety of different proteins. If, for example, the exons of the mRNA sequence that codes for CCR5 (membrane receptor that HIV binds to) are joined in a different way than normal, a different version of CCR5 will be produced, which could alter its shape and reduce the ability of HIV to bind to it. 

Figure 5: Alternative Splicing- Introns are excised and exons are assembled in unique combinations

Once the mRNA sequence is processed, it is ready to be translated into an amino acid sequence. In a ribosome, a tRNA molecule carries an amino acid on one end and a sequence complementary to the codon, known as the anticodon, on the other end. Once an anticodon from a tRNA recognizes its complementary codon, an amino acid (from that same tRNA) is assembled in a process known as translation. Eventually, the result is a chain of amino acids, forming a protein. 

Figure 6: Protein Synthesis

Each codon codes for an amino acid. However, it is possible for several codons to code for the same amino acid. For example, the codons GGU, GGC, GGA, and GGT all code for the amino acid glycine. This redundancy eliminates the effect of a mutation. For example, if GGC is transcribed from CCA instead of GGU, there will be no effect on the protein, since both codons code for the same amino acid. Such a mutation is known as a silent mutation since it does not impact the final polypeptide chain (protein) and can easily go unnoticed.

Mutations

A mutation is a change in the sequence of DNA's nitrogen bases. Environmental stimuli, such as excessive exposure to UV radiation or dangerous chemicals can alter the sequence of bases, causing mutations that can negatively impact cellular functions. This is because any alteration of bases can cause the incorrect amino acid to be substituted in a protein, changing the protein's physical and chemical properties. 

It is a common misconception that all mutations are harmful. Mutations occur all the time, but we hardly realize it since it is possible for several mRNA codons to code for the same amino acid, which will have no effect on the final protein. Mutations can be beneficial in many ways. For example, if a mutation occurs in the mRNA sequence that codes for CCR5 (the cell surface receptor that HIV binds to invade a cell) an individual will never get AIDS. Another example is sickle-cell disease, which occurs when the amino acid valine is substituted in the hemoglobin protein instead of glutamic acid. Individuals who have at least one recessive allele for sickle-cell disease will remain immune to malaria. In this disease, red blood cells are crescent-shaped which hinders their ability to carry adequate oxygen to cells and tissues. Although life-threatening, these crescent shaped red blood cells will not be able to effectively transport the malaria parasite to different parts of the body.

DNA controls our traits and nearly every function of cells and tissues. It is one of the most crucial molecules in the body.

*Identical twins have the same DNA because they develop from the same fertilized egg.

Image References: 

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https://empoweryourknowledgeandhappytrivia.wordpress.com

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“Lumen Learning.” Lumen Learning, https://courses.lumenlearning.com.