Genes and the genetic code_Central dogma

The Central Dogma of Molecular Biology is the foundation of gene expression.
It describes how DNA is transcribed into RNA and translated into proteins, which perform cellular functions.
Although there are exceptions, the central dogma remains a core principle in molecular biology, with applications in medicine, genetics, and biotechnology.

1. Genes and the genetic code Dr. Vividha Raunekar

2. One Gene – One Polypeptide Hypothesis Introduction to the One Gene – One Polypeptide Hypothesis The one gene – one enzyme hypothesis was first proposed by George Beadle and Edward Tatum in 1941, based on their experiments with Neurospora crassa (bread mold) . They induced mutations using X-rays and observed that some mutant strains lost the ability to synthesize certain essential molecules, requiring supplementation in the medium. This led to the conclusion that each gene codes for a specific enzyme , supporting the idea that genes determine the biochemical functions of a cell. Later, as research advanced, it was found that not all proteins are enzymes, and many proteins are made of multiple polypeptide chains, each encoded by different genes. This led to the one gene – one polypeptide hypothesis , which states that each gene encodes a single polypeptide, which may function independently or as part of a larger protein complex .

3. Evidence Supporting the One Gene – One Polypeptide Hypothesis Beadle and Tatum’s Experiment (1941) Used X-rays to create mutants of Neurospora crassa . Some mutants lost the ability to synthesize certain amino acids. When provided with the missing amino acid, the mutant strain could survive. This showed that a specific gene is responsible for producing a specific enzyme in a metabolic pathway. Sickle Cell Anemia (1949) Linus Pauling demonstrated that a single gene mutation leads to a change in hemoglobin structure. A single nucleotide mutation in the HBB gene (which codes for the β-globin polypeptide) changes glutamic acid to valine . This supports the idea that genes control polypeptide sequences. Neurospora Genetic Studies (1950s) Further studies revealed that some proteins consist of multiple polypeptides, each encoded by a separate gene (e.g., hemoglobin has two different polypeptides: α and β chains).

4. Relationship Between Nucleotide Sequence and Amino Acid Sequence a. The Genetic Code The genetic code is a triplet code , where every three nucleotides ( codon ) correspond to a specific amino acid . Features of the genetic code: Triplet nature – Each codon consists of three nucleotides . Degeneracy – Multiple codons can code for the same amino acid (e.g., CUU, CUC, CUA, and CUG all code for leucine). Non-overlapping – Each nucleotide is read only once in a sequential manner. Universal – The same codons specify the same amino acids in nearly all living organisms. Start and stop codons – AUG is the start codon (methionine), and UAA, UAG, UGA are stop codons that signal termination of translation.

5. The Central Dogma of Molecular Biology Introduction The Central Dogma of Molecular Biology describes the flow of genetic information in biological systems, explaining how genetic material is stored, expressed, and translated into functional proteins. Proposed by Francis Crick in 1958 , the central dogma states: DNA → RNA → Protein It highlights the processes of replication, transcription, and translation , which govern the expression of genes and determine cellular functions.

6. Components of the Central Dogma a. DNA (Deoxyribonucleic Acid) – The Genetic Material Structure : Double-stranded helix composed of nucleotides (A, T, G, C) . Base pairing : A-T (Adenine - Thymine), G-C (Guanine - Cytosine). Sugar-phosphate backbone. Function : Stores genetic information and transmits it across generations. Serves as a template for RNA synthesis (transcription) . b. RNA (Ribonucleic Acid) – The Messenger Molecule Types of RNA involved in the Central Dogma : mRNA (Messenger RNA) – Carries genetic information from DNA to ribosomes for protein synthesis. tRNA (Transfer RNA) – Brings amino acids to ribosomes during translation. rRNA (Ribosomal RNA) – Forms the core of ribosomes and facilitates protein synthesis.

7. Key differences from DNA : Single-stranded instead of double-stranded. Ribose sugar instead of deoxyribose. Uracil (U) replaces Thymine (T) . c. Protein – The Functional Output Composed of amino acids linked by peptide bonds . Performs structural, enzymatic, and regulatory roles in cells. The sequence of amino acids in a protein is dictated by the sequence of nucleotides in DNA , following the genetic code.

8. Steps in the Central Dogma a. DNA Replication (DNA → DNA) Occurs in the nucleus (eukaryotes) or cytoplasm (prokaryotes) before cell division. Purpose : To ensure genetic material is accurately passed to daughter cells. Enzymes involved : Helicase : Unwinds the DNA helix. DNA Polymerase : Synthesizes new complementary strands. Ligase : Joins Okazaki fragments on the lagging strand. Process of DNA Replication Initiation – Helicase unwinds DNA at the origin of replication . Elongation – DNA polymerase adds nucleotides in a 5' to 3’ direction . Leading strand : Synthesized continuously. Lagging strand : Synthesized in short Okazaki fragments . Termination – DNA replication ends when the entire molecule is copied.

9. https://www.youtube.com/watch?v=TNKWgcFPHqw

10. Transcription (DNA → RNA) Occurs in the nucleus (eukaryotes) or cytoplasm (prokaryotes) . Purpose : To produce an mRNA transcript that carries genetic information to ribosomes. Enzyme involved : RNA Polymerase . Steps of Transcription Initiation RNA Polymerase binds to the promoter region of a gene (e.g., TATA box). DNA strands unwind, and transcription begins. Elongation RNA polymerase moves along the template strand , synthesizing a complementary mRNA strand (U replaces T). Termination RNA polymerase stops at a termination sequence , releasing the mRNA transcript.

11. https://www.youtube.com/watch?v=8_f-8ISZ164

12. Post-Transcriptional Modifications (Eukaryotes Only) 5' Capping : Addition of a 7-methylguanosine cap at the 5' end for stability and ribosome recognition. Splicing : Removal of introns (non-coding regions) and joining of exons (coding regions) . Polyadenylation : Addition of a poly-A tail at the 3' end for mRNA stability.

13. c. Translation (RNA → Protein) Occurs in ribosomes (cytoplasm or rough ER in eukaryotes). Purpose : Converts the mRNA sequence into a polypeptide (protein). Key components : mRNA : Carries the genetic code. tRNA : Brings specific amino acids to ribosomes. Ribosomes : Site of protein synthesis. Steps of Translation Initiation The ribosome binds to the mRNA at the start codon ( AUG ). The first tRNA carrying methionine binds to the start codon. Elongation tRNA molecules bring amino acids to the ribosome. Ribosome forms peptide bonds between amino acids. The ribosome moves along the mRNA, adding amino acids one by one. Termination Translation stops when a stop codon (UAA, UAG, or UGA) is reached. The polypeptide chain is released.

14. Post-Translational Modifications Folding – Proteins fold into their functional 3D shape (assisted by chaperone proteins ). Chemical modifications – Phosphorylation, glycosylation, acetylation. Cleavage – Some proteins need enzymatic processing (e.g., proinsulin to insulin). https://www.youtube.com/watch?v=gG7uCskUOrA

15. 4. Extensions and Exceptions to the Central Dogma a. Reverse Transcription (RNA → DNA) Some viruses, like retroviruses (HIV) , use reverse transcriptase to convert RNA back into DNA. This contradicts the original dogma but is now well-established in molecular biology. b. Non-Coding RNA (ncRNA) Some genes do not code for proteins but produce functional RNAs instead, such as: rRNA (Ribosomal RNA) – Essential for ribosome function. tRNA (Transfer RNA) – Brings amino acids during translation. microRNA (miRNA) and siRNA – Regulate gene expression. c. Alternative Splicing A single gene can produce multiple proteins by rearranging exons during splicing. Example: The Drosophila Dscam gene can generate thousands of different protein isoforms. d. Epigenetic Regulation DNA methylation and histone modification can regulate gene expression without changing the DNA sequence.

16. Significance of the Central Dogma Explains how genetic information flows within a cell. Basis for genetic engineering, gene therapy, and biotechnology. Helps understand genetic diseases caused by mutations (e.g., sickle cell anemia, cystic fibrosis). Used in forensic science, personalized medicine, and synthetic biology. Conclusion The Central Dogma of Molecular Biology is the foundation of gene expression . It describes how DNA is transcribed into RNA and translated into proteins , which perform cellular functions. Although there are exceptions, the central dogma remains a core principle in molecular biology , with applications in medicine, genetics, and biotechnology.

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