Lecture Note_Unit V Biochemistry PDF

Descriptive title: BIOCHEMISTRY Prepared by: Tricia L. Gundran Unit V. NUCLEIC ACIDS  LESSON OBJECTIVES  Describe the molecular structure of DNA and RNA, including their components;  Explain the processes of replication, transcription, and translation, and ho...

Descriptive title: BIOCHEMISTRY Prepared by: Tricia L. Gundran Unit V. NUCLEIC ACIDS  LESSON OBJECTIVES  Describe the molecular structure of DNA and RNA, including their components;  Explain the processes of replication, transcription, and translation, and how genetic information is transferred from DNA to RNA to protein;  Demonstrate understanding how nucleic acids regulate gene expression, including the role of promoters, enhancers, and transcription factors; and  Explain the potential impact on protein function and organismal traits; DIFFERENTIATE A GENE FROM DNA  What is a gene? ❑ A gene is a segment of a DNA ❑DNA carries the genetic instructions (hereditary materials) ❑Can be replicated or copied What is a gene? ❑ Likea series of letters strung along each edge (have proteins) ❑Like an instruction book Karyotype is an individual’s set of chromosomes. The term also refers to a laboratory-produced image of a person’s chromosomes isolated from an individual cell and arranged in numerical order. A karyotype may be used to look for abnormalities in chromosome number or structure. What is a CHROMOSOME? ❑ Chromosomes are long strands of a chemical substance called DNA ❑ 46 ❑ Paired chromosomes are numbered from 1 to 22 according to size. These are autosomes. GENETICS ❑Austrian Monk ❑Born in Czech Republic GREGOR JOHANNE MENDEL ❑ Study about genes and heredity ❑ Pea plants (Pisum sativum) have many varieties and produces faster ❑ Worked out the basic laws of inheritance through experiments like pea plants DIFFERENTIATE A NUCLEIC ACID FROM A NUCLEOTIDE What is a nucleotide? ❑ A building block of nucleic acids (DNA and RNA) ❑Has five-carbon sugar backbone, a phosphate group and nitrogen bases What is a nucleotide? What is a NUCLEOSIDE? ❑Structural subunit of nucleic acids ❑Can either be pyrimidine or purine ❑Nucleic acids contain nucleoside HEREDITY  What is heredity?  The transmission of traits from one generation to the next.  Genetic heritage passed down from our biological parents  Traits are determined by genes (two copies: from sperm and from egg)  A single gene can have variants (allele; dominant or recessive) What is heredity?  is the passing of traits from parent to offspring. Molecules of DNA carry information that codes for various proteins. These proteins interact with the environment, causing observable patterns of life. HOW DOES HEREDITY WORKS?  Genes encode the information for making specific proteins, which are responsible for the specific traits of an individual.  When organisms reproduce, genetic information is transferred to their offspring.  In species that reproduce sexually, each cell contains two variants of each chromosome, one inherited from each parent. HOW DOES HEREDITY WORKS?  Thus sexual reproduction gives rise to a new combination of chromosome pairs with variations between parent and offspring.  Veryrarely, mutations also cause variations, which may be harmful, neutral, or occasionally advantageous for an individual. When mutation affects one’s gene, a genetic disorder may occur Take note of the following terms  Disease: A particular distinctive process in the body with a specific cause and characteristic symptoms.  Disorder: Irregularity, disturbance, or interruption of normal functions.  Syndrome: A number of symptoms occurring together and characterizing a specific disease. RELATIONSHIP OF PROTEINS AND NUCLEIC ACIDS CENTRAL DOGMA OF LIFE  Protein synthesis is the process where a sequence of DNA is used to build a protein from individual amino acids. The first step in this process is called TRANSCRIPTION, where a coding region of DNA is converted to messenger RNA (mRNA).  During transcription, mRNA is made from the DNA sequence following the base pair rule, except RNA does not contain the base Thymine, but instead has Uracil. The mRNA then leaves the nucleus and goes to a ribosome in the cell's cytoplasm.  The ribosome reads the message three bases at a time, called a CODON. Each codon will specify a single amino acid. The amino acids are joined together and folded into a protein, a process called TRANSLATION  CODON WHEEL A single codon is used to signal the beginning of protein synthesis. It is commonly called the START CODON. There are three codons that signal the end of synthesis, these are called STOP codons (there are three stop codons) GENE EXPRESSION GENE EXPRESSION  Information from a gene is used to build a functional product in a process called gene expression.  Occurs via the transcription of RNA molecules that code for proteins or non-coding RNA molecules that serve other functions. GENE EXPRESSION  A gene that encodes a polypeptide is expressed in two steps. In this process, information flows from DNA to RNA to protein, a directional relationship known as the central dogma of molecular biology. GENE EXPRESSION Classically, through observing phenotype. An example is to measure a protein activity. If a protein activity can be measured, the gene that encodes for that protein is probably turned on or we can define it as turned on.  Recent technology: The ability to measure mRNA expression of every gene in the entire genome National human genome research institute. (2024). Gene expression. https://www.genome.gov/genetics-glossary/Gene- Expression GENE EXPRESSION  Functionally eliminates particular cell from doing certain functions  Constitutive or housekeeping genes carry out basic metabolic processes  Regulated genes are turned on or off as needed  Inducible  Repressible  These genes along with their regulatory sequences of DNA are called Operon https://www.slideserve.com/tieve/regulation-of-gene-expression  Constitutive genes  It controls the ability of DNA to replicate, express itself, and repair itself.  It controls protein synthesis and an organism’s central metabolism Hoopes, L. (2014). Gene expression and regulation. https://www.nature.com/scitable/topic/gene-expression-and- regulation-15/  Regulated genes  For prokaryotes, most regulatory proteins are negative and therefore turn genes off.  Some of them have ligand attached to them to be able to bind  Some of them are specific to one gene and others act more widely Hoopes, L. (2014). Gene expression and regulation. https://www.nature.com/scitable/topic/gene-expression-and-regulation- 15/  Regulated genes  For eukaryotes, cell-cell differences are determined by expression of different sets of genes. Hoopes, L. (2014). Gene expression and regulation. https://www.nature.com/scitable/topic/gene-expression-and-regulation- 15/  Regulated genes For instance, an undifferentiated fertilized egg looks and acts quite different from a skin cell, a neuron, or a muscle cell because of differences in the genes each cell expresses. Cancer cell acts different from a normal cell for the same reason: It expresses different genes. Hoopes, L. (2014). Gene expression and regulation. https://www.nature.com/scitable/topic/gene-expression-and-regulation-15/ Research Review on Epigenetic Clock Marks Age of Human Tissues and Cells  DNA changes predict longevity National Institutes oof Health. (2016). DNA changes predict longevity. https://www.nih.gov/news-events/nih-research-matters/dna-changes- predict- longevity#:~:text=Certain%20DNA%20changes%20can%20better%20pr edict%20a%20person%E2%80%99s,evaluate%20methods%20for%20slo wing%20the%20rate%20of%20aging. In Asia, the average life expectancy is 72 yrs. old  DNA changes predict longevity EPIGENETIC CLOCK MARKS AGE OF HUMAN TISSUES AND CELLS RESEARCH GAP For years, scientists have been trying to gauge aging based on changes inside our cells. Reference: DNA methylation age of human tissues and cell types. (2013). Genome Biol, 21;14(10):R115. [Epub ahead of print] PMID: 24138928. Therapeutic targets in the aging process. Reference: Saul, D. & Konsinsky, R. (2020). Epigenetics of aging and aging-associated disease, MDPI, 22(1), 401. https://doi.org/10.3390/ijms22010401  Our DNA changes as we age.  Epigenetic—they modify DNA without altering the genetic sequence itself. One type of epigenetic modification, called DNA methylation, roughly reflect a person’s age.  EPIGENETIC CLOCK MARKS AGE OF HUMAN TISSUES AND CELLS RESEARCH PROBLEM Examined the relationship between DNA methylation and aging METHODOLOGY Developed an age predictor based on 353 specific DNA sites where methyl groups increased or decreased with age Analyzed nearly 6, 000 samples from 20 different cancers RESULTS Computed biological age based on DNA methylation closely predicted the chronological age of numerous tissues and cells to within a few years except for skeletal muscle, heart tissue, and breast tissue. Cancer greatly affected DNA methylation age.  DNA changes predict longevity EPIGENETIC CLOCK MARKS AGE OF HUMAN TISSUES AND CELLS LIMITATIONS of the STUDY To asses whether DNA methylation is a marker of aging or itself affects aging What is the future direction of the study?  First step towards developing targeted methods to slow the process Trends in the gene expression  1. Barcoding Technique for RNA sequencing  Dimmer, O. (2024). Researchers improve measurement of gene expression in single cells. https://www.msn.com/enus/health/other/re searchers-improve-measurement-of-gene- expression-in-single-cells/ar- BB1oVnQg?ocid=BingNewsVerp To identify which cells are singlets What’s the point of knowing the true singlets? Move outside the traditional methods Examines the genome of a cell population  Dimmer, O. (2024). Researchers improve measurement of gene expression in single cells. https://www.msn.com/enus/health/other/re searchers-improve-measurement-of-gene- expression-in-single-cells/ar- BB1oVnQg?ocid=BingNewsVerp  What’s the future prospect of this study? Single-cell sequencing technologies, snapshot all mRNA Measure a transcriptome of each cell Mutations and cancerous Epigenome variations occurring during embryonic development  Dimmer, O. (2024). Researchers improve measurement of gene expression in single cells. https://www.msn.com/enus/health/other/researchers-improve-measurement-of-gene-expression-in-single-cells/ar- BB1oVnQg?ocid=BingNewsVerp 2. Researchers discover an immune response protecting some from COVID-19  Triggered a high expression of a gene  Human cell atlas project  36 participants of the study Leitch, C. (2024). Researchers discover an immune response protecting some from COVID-19. https://www.labroots.com/trending/cell-and- molecular-biology/27327/researchers-discover- immune-response-protecting-covid-19  How did they do it?  Six study volunteers were exposed to virus Patterns in T cell receptor activation showed. What is the significance of this study? To build a Human Cell Atlas To develop treatments & vaccines mimicking the showed natural protective responses of humans Leitch, C. (2024). Researchers discover an immune response protecting some from COVID-19. https://www.labroots.com/trending/cell-and-molecular- biology/27327/researchers-discover-immune-response-protecting-covid-19 A bittersweet supply chains Statistics says…  3. Researchers compile Cacao Gene Atlas to help plant breeders boost chocolate tree  Pennsylvania State University  Compiled dataset of replicated transcriptomes Mulhollem, J. (2024). Researchers compile Cacao gene atlas to help plant breeders boost chocolate tree. https://phys.org/news/2024-06-cacao-gene- atlas-breeders-boost.html  What is the objective of the study? Develop resistant strains of Cacao The atlas is used to simulate how knocking out or enhancing a gene may influence the plant How did they do it? Extracted RNAs and sequenced transcriptomes from 123 different tissues and stages development representing major organs and developmental stages Mulhollem, J. (2024). Researchers compile Cacao of the Cacao lifecycle gene atlas to help plant breeders boost chocolate tree. https://phys.org/news/2024-06-cacao-gene- Exposed to biotic and abiotic stressors atlas-breeders-boost.html AS A MATTER OF FACT, Although it is not a well-known cocoa producing country, the Philippines archipelago was the first country in Asia to have cacao introduced, with the fruit first brought into the Philippines 350 years ago in 1670 by Spanish colonizers during the Acapulco-Manila trade.  What is the future direction of this study? To widen the resources in the gene expression of this crop Mulhollem, J. (2024). Researchers compile Cacao gene atlas to help plant breeders boost chocolate tree. https://phys.org/news/2024-06-cacao-gene- atlas-breeders-boost.html  4. Method identifies genes regulating plant traits without experimental intervention What is its objective? By genetically manipulating a plant’s transcription factors, researchers can increase or decrease the amount of oil produced in its seeds. Reference:: Ranjan R, Srijan S, et al. Organ-delimited gene regulatory networks provide high accuracy in candidate transcription factor selection across diverse processes. PNAS. 2024;121(18):e2322751121. doi: 10.1073/pnas.2322751121 Reference:: Ranjan R, Srijan S, et al. Organ-delimited gene regulatory networks provide high accuracy in candidate transcription factor selection across diverse processes. PNAS. 2024;121(18):e2322751121. doi: 10.1073/pnas.2322751121 Reference:: Ranjan R, Srijan S, et al. Organ-delimited gene regulatory networks provide high accuracy in candidate transcription factor selection across diverse processes. PNAS. 2024;121(18):e2322751121. doi: 10.1073/pnas.2322751121  Limitations of the study Arabidopsis as the model Corn Tomato Only Computational approach What is the significance of this study? Focuses on a genetic pathway that regulates how plants work and store oil in their seeds For food and biofuel Reference:: Ranjan R, Srijan S, et al. Organ-delimited gene regulatory networks provide high accuracy in candidate transcription factor selection across diverse processes. PNAS. 2024;121(18):e2322751121. doi: 10.1073/pnas.2322751121  HOW CAN WE OBTAIN NUCLEIC ACIDS? FOR YOUR INFORMATION Seeds, grain, and fish eggs are good sources of the genetic material, DNA. Muscle tissue is an excellent source of nucleotides, such as the energy source ATP. Extracts of meat and yeast have very high purine contents but are usually eaten in small quantities. GENETIC DISORDERS Genetic disorders occur when a mutation (a harmful change to a gene, also known as a pathogenic variant) affects your genes or when you have the wrong amount of genetic material. Genes are made of DNA (deoxyribonucleic acid), which contain instructions for cell functioning and the characteristics that make you unique. Chromosomal disorder Affects the structures that hold your genes within each cell (chromosomes) Complex (multifactorial) Combination of gene mutations and other factors like chemical exposure, diet, certain medications, alcohol use, etc. Single-gene (monogenic) Occurs from a single gene mutation Chromosomal disorder Down syndrome, fragileX syndrome, Klinefelter syndrome, triple-X syndrome, turner syndrome, trisomy 18, trisomy 13 Complex (multifactorial) Late onset Alzheimer’s disease, arthritis, autism spectrum disorder, cancer coronary artery disease, diabetes, migraine headaches, spina bifida, isolated congenital heart defects Single-gene (monogenic) Cystic Fibrosis, deafness present at birth (congenital), Duchenne muscular dystrophy, familial hypercholesterolemia, hemochromatosis, neurofibromatosis type 1, sickle cell disease, Tay Sachs disease Chromosomal disorder KLINEFELTER SYNDROME a common condition that results when a person assigned male at birth has an extra copy of the X sex chromosome instead of the typical XY. Common characteristics: Usually have small, firm testicles and a small penis Low sperm count or no sperm Difficulty expressing thoughts and feelings TURNER SYNDROME a condition that affects only females, results when one of the X chromosomes (sex chromosomes) is missing or partially missing. Turner syndrome can cause a variety of medical and developmental problems, including short height, failure of the ovaries to develop and heart defects. Complex disorder SPINA BIFIDA a condition that occurs when the spine and spinal cord don't form properly. It's a type of neural tube defect. Spina bifida is more common among Hispanic people and white people. This is due to too little folate (Vitamin B-9) in the pregnant person’s body. Late onset Alzheimer’s disease a common form of dementia that starts at the age of 65. Common characteristics: Memory and cognition issues Impaired judgment and other symptoms Rare cases is early as 30. Single-gene disorder Cystic Fibrosis is an inherited disorder that causes severe damage to the lungs, digestive system and other organs in the body. It affects the cells that produce mucus, sweat and digestive juices. Duchenne Muscular Dystrophy a condition that causes skeletal and heart muscle weakness that quickly gets worse with time. Signs and Symptoms of Duchenne Muscular Dystrophy TRENDS AND ISSUES IN THE STUDY OF NUCLEIC ACIDS 1. TREND Link: https://www.msn.com/en- in/health/other/this-japanese-diet- can-stop-cancer-cell-growth-says- study/ar- AA1tx0Oo?ocid=BingNewsVerp 2. TREND Link: https://www.eurekalert.org /multimedia/1039308 Salmon Milt is the white fluid containing millions of sperm that male salmon release Torula Yeast Also known as Candida utilis For the production of beer and wine 3. TREND Link: https://www.v erywellhealth.c om/gene- therapy- 5214362 4. TREND Link: https://news.stanf ord.edu/stories/20 24/06/stanford- explainer-crispr- gene-editing-and- beyond Link: https://news.stanf ord.edu/stories/20 24/06/stanford- explainer-crispr- gene-editing-and- beyond