Genetic Engineering and Human Health

DNA Biology

The history of DNA (Deoxyribonucleic Acid) began in the mid 19 ^th century with Friedrich Miescher's discovery of a substance inside the nucleus. Not until 1919, was the name "nucleotide" coined when Phoebus Levene for a molecule containing deoxyribose sugar, phosphate, and various bases. Once Rosalind Franklin's x-ray diffraction images were seen by James Watson and Francis Crick, the structure of DNA was soon discovered. In 1953, Watson and Crick revealed that DNA is a coiled double helix composed of two complementary strands held together by hydrogen bonds. ⁶ A single strand of DNA is a long polymer of nucleotide units. The four bases in DNA are purines (guanine and adenine) and pyrimidines (thymine and cytosine). The two strands of DNA are complementary but antiparallel running 5' to 3' direction and its complement running from 3' to 5'. ⁷

In the human cell, DNA carries instructions for all cellular functions. Humans have about 50 trillion cells. Each cell has a set of 23 chromosomes tightly coiled inside the nucleus of cells. ⁸ As humans grow or as cells need replacement they undergo the process of mitotic division to proliferate or replace cells that have aged or are damaged. This process is achieved through mitotic division. In mitosis, a mature cell undergoes changes which allow it to replicate (make exact copies) of its DNA: the two copies are separated into two cells, which each contain an exact copy of the original DNA. The process of replication is important because it allows the cell to maintain a diploid state (having a set of chromosome inherited from their parents), and allows all cells in the body to contain the exact same DNA. All cells except those destined to be sperm or egg cell undergo mitotic division since sex cells contain half the amount of chromosomes. Thus 22 out of 23 are called autosomes and the last is the sex chromosome since they determine a person's gender.

In a strand of DNA there are approximately 3 billion bases. Of these bases are segments of DNA which specifies codes for protein synthesis called genes. There are ~25, 000 genes coding for various cellular functions (i.e. enzymatic activity) and traits like eye color. Each gene is its own instruction set and the length of a gene varies depending on the number of base pairs. Within a gene segment are control regions for activation and deactivation of the gene, short start and stop codes for control of protein synthesis, and the specific sequence that encodes the sequence of specific amino acids in the protein. ⁹

Transcription and Translation

The process of making proteins is an essential topic covered in all Biology classes. This is due to the importance of proteins for cell structure, function, and regulation. In order to make new proteins, 20 amino acids combine in a specific order to create long chains of unique protein products. How they are arranged into amino acids chains are determined by their original gene code. The "Central Dogma" of Biology describes this process. The Central Dogma states that DNA is transcribed into RNA and RNA is translated into Proteins. ¹⁰

During transcription, the DNA gene segment is transcribed into mRNA (messenger RNA). Transcription begins with the unzipping of the double helix. An enzyme RNA polymerase binds to specific starting segments of the single stranded DNA called a promoter region. The single strand of DNA is transcribed into mRNA, where thymine is replaced by a new base - uracil. Uracil binds to its complement adenine. Once a terminator sequence is reached by the RNA polymerase, the mRNA strand is released from the DNA, completing the transcription process. ¹¹

When mRNA leaves the nucleus for the cytoplasm of the cell, the process of translation begins. Segments of the mRNA not needed for protein synthesis (introns) are excised, leaving the coding "exons" regions available to complete the synthesis of proteins. Free amino acids within the cytoplasm are linked together inside a ribosome, using the mRNA template. The ribosome serves as the cell factory through which the new polypeptide (a chain of amino acids) is formed. This process occurs in three steps: Initiation, Elongation, and Termination. During Initiation, small ribosomal units with tRNA (transfer RNA) bounded to a methionine amino acid begins searching for the start sequence on the mRNA strand. Once found, the large ribosomal unit binds to complete the ribosome and protein synthesis proceeds. In the second step, Elongation, new tRNAs with new amino acids sequences (anticodons) attach to its corresponding set of three nucleotide sequence (codons) on the mRNA. As more anticodons match to its codons, chains of polypeptide are added, causing the polypeptide to elongate. A DNA codon table shows exactly which anticodon-amino acid corresponds to a specific codon. This same codon table also shows the sequence for start and stop codons. Once a stop codon is reached, the fully elongated polypeptide or protein chain is released and the ribosome unbinds from the mRNA strand completing the Termination stage of translation. Though the protein is complete, it may require additional factors or steps (called post-translational modifications) to activate the protein for its purpose. ¹²