GENETICS: Introduction, Cell Cycle, Mitosis & Meiosis - PDF

INTRODUCTION TO GENETICS What is genetics? Genetics is a study of heredity in general and of genes in particular. Genetics forms one of the central pillars of biology and overlaps with many other areas, such as agriculture, medicine, and biotechnology....

INTRODUCTION TO GENETICS What is genetics? Genetics is a study of heredity in general and of genes in particular. Genetics forms one of the central pillars of biology and overlaps with many other areas, such as agriculture, medicine, and biotechnology. HISTORICAL CONTEXT Swiss physician Friedrich Miescher discovered a substance he called ‘nuclein’ in 1869. Later, he Greek philosophers explored the idea of human isolated a comparatively purer sample of this same inheritance some 1600 years after 5000 BC. The material from the sperm of salmon. notable Aristotle suggested that traits acquired In 1889, his pupil, Richard Altmann renamed throughout an organism’s lifetime could be nuclein to ‘nucleic acid’. This substance was found transmitted to their offspring. Aristotle to exist only in the chromosomes. supplemented this hypothesis with the theory of This discovery built on earlier work by Walter ‘pangenesis’ which described how these traits Flemming who described the appearance and could be passed on; particles called ‘gemmules’ behavior of chromosomes in 1882 (each organ of the body sends it copy in the In 1902, Theodor Boveri and Walter Sutton gametes) encapsulated these traits and allowed independently postulated that chromosomes were them to be transmitted to reproductive cells). not only the carriers of hereditary units but were Aristotle’s theory was rejected by August organized so that different locations (gene loci) of Weismann, a german evolutionary biologist, by the chromosomes corresponded to specific proposing the Germ Plasm Theory (1883) - germ hereditary traits. Boveri did this by examining plasm, which is independent from all other cells of chromosomal behavior during cell division and the body (somatoplasm), is the essential element gamete formation. This formed the basis of of germ cells (eggs and sperm) and is the hereditary cytogenetics which describes the structure, material that is passed from generation to function and inheritance of chromosomes. generation In 1929 Phoebus Levene at the Rockefeller Gregor Mendel: The 'Father of Genetics’ Institute identified the components that make up a - a monk who performed a meticulous series of DNA Molecule. Those components are: The Four experiments with pea plants in 1857. Bases (Adenine, Cytosine, Guanine, Thymine), - selected specific characteristics of pea plants Sugar (Deoxyribose, Ribose), and Phosphate. He to study (plant height, seed texture, seed color, showed that the components of DNA were linked in flower color, pea-pod size, pea-pod color, and the order phosphate-sugar-base. Crucially, he flower position) distinguished the two ribose subtypes – - he repeated this over two generations of plants deoxyribose and ribose. Levene coined the and found that he could obtain consistent arrangement of the sugar, base and phosphate ratios of traits. group a ‘nucleotide”. - In turn, he deduced four important principles of inheritance: 1. Hereditary determinants are called genes. 2. Genes exist in pair, called alleles which may be dominant or recessive. 3. Genes are segregated in the gametes which are consequently carriers of only one gene pair. 4. Fertilization, in which two gametes fuse, is random.  In 1949 André Boivin and his students Colette A DECADE LATER and Roger Vendrely found that the nuclei of germ cells contained only half the amount of DNA than (notable discoveries beyond the double helix) that of somatic cells. Robert W. Holley, Har Gobind Khorana and Marshall W. Nirenberg won a Nobel prize for their work deciphering how DNA related to protein synthesis. They established the central dogma of information transfer from DNA to RNA to protein. In 1977, Frederick Sanger, Allan Maxam, and Walter Gilbert developed methods to sequence DNA. This was supplemented in 1983 by Kary Mullis, In the 1940s Erwin Chargaff found that the base who invented the polymerase chain reaction (PCR) composition (adenine, guanine, cytosine, and to amplify DNA. thymine) differed between species and that ratios Together these methods paved the way for between them were invariable; the quantity of sequencing of the human genome which began in adenine was equal to that of thymine. The same 1990 and was completed 13 years later, in full. ratio of 1:1 was seen for cytosine and guanine. This discovery later became known as Chargaff’s Rule. TODAY In 1952, British researcher Rosalind Franklin crystallized a molecule of DNA. From the X-ray the focus on DNA has exploded to include ways of diffraction images Franklin obtained, she ‘editing’ the genome, using novel methods to demonstrated that DNA contained a regularly change the information it encodes in highly repeating helical structure. The images allowed specific ways. precise calculations of the molecular spacing in Further, lesser-known areas of the genome are DNA under study; the field of epigenomics is rapidly Building on Franklin’s work two scientists, James expanding, allowing us to understand how and why Watson and Francis Crick, made a model of the genome behavior differs substantially between DNA structure approximately 2 years later. Their individuals. model was that of a double helix that consisted of evenly spaced pairs of bases connecting the two strands. It was possible to predict the measurements between bases and the number of bases per turn; further, there were strict base pairing rules. To account for their measurements, they discovered that Thymine could only pair with Adenine and Guanine with Cytosine. This concurred with Chargaff's rule. Chargaff's rules state that DNA from any cell of all organisms should have a 1:1 ratio (base Pair Rule) of pyrimidine and purine bases and, more specifically, that the amount of guanine is equal to cytosine and the amount of adenine is equal to thymine.  CELL (The fundamental unit of life) Cytoplasm is a gel-like matrix containing water, salts, proteins, and other molecules. It occupies the intracellular space between the cell membrane and the nucleus. It plays a crucial role in biochemical reactions, energy production, and substance transport. Essential for cellular metabolism, it provides structural support to the cell. Cell - is the basic structure of the PROTEIN SYNTHESIS body. The human body is built of billions and trillions of cells. Cells Building and repairing cellular structures, of various organs vary according to regulating biological processes, and expressing their function. Each cell contains specific characteristics of each organism. the hereditary material and can Ribosomes are essential make copies of itself by organelles for cellular functioning reproducing and multiplying. After and survival. Ribosomes are a specific life span, the old cells die off. located in the cytoplasm and the rough endoplasmic reticulum. STRUCTURE AND BASIC FUNCTIONS They synthesize proteins using the genetic information from These components work together to maintain cellular messenger RNA (mRNA), which is homeostasis and perform essential life activities crucial for cellular structure, function, and regulation Endoplasmic reticulum - network of interconnected membranes that extends from the nuclear membrane to the cell membrane. It plays a fundamental role in the transport, processing, and distribution of proteins and lipids within the cell. Cell membrane - surrounds the cell and is a selective barrier There are two main types of ER: between the interior and the exterior. Its primary role lies in - The Rough Endoplasmic Reticulum (RER) is regulating the passage of studded with ribosomes and is involved in the substances, including nutrients synthesis and modification of proteins. and waste materials. Within it, - The Smooth Endoplasmic Reticulum (SER) specialized proteins play a crucial specializes in lipid synthesis, carbohydrate role in facilitating molecular metabolism, and detoxification transport and cellular communication. Golgi apparatus - Key in the Cell nucleus - that houses DNA, processing and packaging of located in the center of eukaryotic proteins and lipids produced in the cells. Its primary function is to endoplasmic reticulum. store and safeguard genetic Composed of a series of flattened information, controlling gene sacs called cisternae, it acts as the expression and DNA replication. It 'shipping center' of the cell, sorting also contains the nucleolus, which and packaging proteins into is involved in ribosome synthesis vesicles for transport and distribution. It synthesizes carbohydrates and lipoproteins and is essential for maintaining the cell's internal balance filaments) and provides support and and facilitating communication with the outside. enables movement in eukaryotic cells. Its specific functions encompass ENERGY SUPPLY stability, intracellular transport, and To carry out vital functions and necessary contraction. Furthermore, it regulates metabolic processes essential for the proper cellular shape and plays a role in division, migration, and functioning of the cell and/or organism. communication. Mitochondria - Present in eukaryotic Flagella and cilia have specialized animal and plant cells. Their primary structures for movement. They are function is energy generation through elongated and enable locomotion in cellular respiration (ATP production). The liquid environments, whereas cilia double membrane of mitochondria are shorter and create coordinated allows for the organization of various flow on the cell surface. Composed stages of the respiratory chain, making it of microtubules in a '9+2' pattern, crucial for cellular function and survival. they are essential for sperm motility. Chloroplasts - Exclusive to plant STORAGE AND TRANSPORTATION cells and photosynthetic They manage nutrients, eliminate waste, and organisms, chloroplasts carry regulate metabolic processes. out photosynthesis, converting solar energy into chemical Vacuoles - membrane-bound organelles energy. During photosynthesis, found in plant cells and some animal cells. they synthesize glucose and They store nutrients, water, ions, and waste other organic compounds using carbon dioxide and water, materials, regulating turgor pressure and releasing oxygen as a byproduct. They are responsible for osmotic balance. Vacuoles can also be the crucial production of oxygen that sustains the planet. involved in the digestion of substances and serve as a defense mechanism against CELLULAR DIGESTION predators by containing toxins. It involves breaking down molecules and unwanted Vesicles and endosomes - membranous materials, enabling the recycling of nutrients and vesicles that transport specific materials cellular maintenance. between organelles and the cell Peroxisomes contain enzymes that membrane. Vesicles: They transport degrade hydrogen peroxide and toxic materials from the endoplasmic reticulum compounds, thereby protecting the cell and the Golgi apparatus to other from oxidative damage. Additionally, destinations. Endosomes: They capture they play a role in the synthesis and and distribute materials for degradation, recycling, or their degradation of lipids and bile acids, regulating lipid incorporation into metabolic pathways. metabolism and overall homeostasis. DIFFERENCE BETWEEN DNA, CHROMOSOMES, AND Lysosomes contain digestive enzymes that GENES break down molecules and unwanted CHROMOSOMES cellular materials. They facilitate cellular digestion, by disposing of waste, recycling Within the nucleus, the DNA strands are tightly nutrients, and defending against packed to form chromosomes. During the cell pathogenic invasions division, the chromosomes are visible. SUPPORT AND MOVEMENT Each chromosome has a constriction point called the centromere from where two arms are formed. Maintaining cellular shape, enabling cellular The short arm of the chromosome is labeled the “p movement and division, are essential for its arm.” The long arm of the chromosome is labeled functioning and survival. the “q arm.” Humans typically have 23 pairs of chromosomes, Cytoskeleton- is composed of protein filaments for a total of 46. Twenty-two of these pairs, called (microtubules, microfilaments, and intermediate  autosomes, look the same in both males and Adenine-Uracil – 2 hydrogen bonds (RNA) females. The chemical structures of Thymine and Cytosine The 23rd pair is called the sex chromosomes and are smaller, while those of Adenine and Guanine differs between males and females. Females have are larger. two copies of the X chromosome or XX, while Size and structure of the specific nucleotides males have one X and one Y chromosome. cause Adenine and Thymine to always pair together while Cytosine and Guanine always pair together. DNA DNA in humans contains around 3 billion bases. is responsible for building and maintaining your These bases are sequenced differently for various human structure. information that needs to be transmitted. GENES HUMAN CHROMOSOMES Genes are hereditary material that lies within the In humans, 23 such cell nucleus. Genes, which are made up of DNA, chromosomes occur in pairs act as instructions to make molecules called and thus totalling 46 proteins. chromosomes. These 23 The Human Genome Project has estimated that pairs can be divided into humans have between 20,000 and 25,000 genes. autosomes and allosomes. Every person has two copies of each gene, one The first 22 pairs come under autosomes, and the 23rd pair is the allosome or sex chromosome. inherited from each parent. 23 Chromosomes and Their Functions THE PROPERTIES OF DNA With advancing research techniques, it has DNA, or deoxyribonucleic acid, is the hereditary become possible to locate and analyse the material that lies within the nucleus of all cells in functions of all the 23 chromosomes in humans. humans and other living organisms. DNA contains four chemical bases/nitrogenous bases: - Adenine (A) – purine (double ring) - Guanine (G) - purine - Cytosine (C) – pyrimidine (single ring) - Thymine (T) - pyrimidine - (including Uracil of RNA DNA BASE PAIRS DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. The Adenine - Thymine base pair is held together by 2 hydrogen bonds while the Guanine - Cytosine base pair is held together by 3 hydrogen bonds.  FUN FACT The Human Genome Project has determined that humans have an estimated 30,000 genes. karyotype is the entire set of chromosomes of a cell or individual, as seen during mitotic metaphase. It helps to determine the size, shape, number and type of chromosomes. Idiogram is nothing but the diagrammatic representation of a karyotype. Cytological maps or physical maps determine the physical locations of a gene in a chromosome with the help of genetic markers. Cytological maps are more accurate in terms of genome representation than genetic maps. The genetic map provides insight into the nature of various regions of the chromosome and is comparatively less efficient.  CELL CYCLE. MITOSIS. MEIOSIS ❖ gene - basic unit of heredity; codes for a specific trait ❖ locus - the specific location of a gene on a chromosome (locus - plural loci) ❖ genome - the total hereditary endowment of DNA of a cell or organism ❖ somatic cell - all body cells except reproductive cells ❖ gamete - reproductive cells (i.e. sperm & eggs) ❖ chromosome - elongate cellular structure composed of DNA and protein - they are the vehicles which carry DNA in cells ❖ diploid (2n) - cellular condition where each chromosome type is represented by two TERMS AND CONCEPTS TO UNDERSTAND homologous chromosomes ❖ haploid (n) - cellular condition where each Cell division involves the distribution of identical chromosome type is represented by only one genetic material, DNA, to two daughters cells. chromosome What is most remarkable is the fidelity with which ❖ homologous chromosome - chromosome of the the DNA is passed along, without dilution or error, same size and shape which carry the same type of from one generation to the next. genes CORE CONCEPTS: ❖ chromatid - one of two duplicated chromosomes connected at the centromere All Organisms Consist of Cells and Arise from ❖ centromere - region of chromosome where Preexisting Cells microtubules attach during mitosis and meiosis - Mitosis is the process by which new cells are generated. CHROMOSOME STRUCTURE - Meiosis is the process by which gametes are generated for reproduction. The Cell Cycle Represents All Phases in the Life of a Cell - DNA replication (S phase) must precede mitosis, so that all daughter cells receive the same complement of chromosomes as the parent cell. - The gap phases separate mitosis from S phase. This is the time when molecular signals mediate the switch in cellular activity. - Mitosis involves the separation of copied chromosomes into separate cells Unregulated Cell Division Can Lead to Cancer composed of DNA and protein (histones) all tightly - Cell-cycle checkpoints normally ensure that wrapped up in one package DNA replication and mitosis occur only when duplicated chromosomes are connected by a conditions are favorable and the process is centromere working correctly. Chromosomes1&2 are homologous chromosomes Chromosomes 3 & 4 are homologous - Mutations in genes that encode cell-cycle chromosomes proteins can lead to unregulated growth, Chromosomes 1 & 3 came from the mother resulting in tumor formation and ultimately Chromosomes 2 & 4 came from the father invasion of cancerous cells to other organs. In order to better understand the concept of cell division and genetics, some basic definitions are in order:  THE CELL CYCLE Actively dividing eukaryote cells pass through a series of stages known collectively as the cell PROPHASE cycle: Prophase occupies over half of mitosis. The two gap phases (G1 and G2); an S (for synthesis) nuclear membrane breaks down to form a number phase, in which the genetic material is duplicated; of small vesicles and the nucleolus disintegrates. and an M phase, in which mitosis partitions the A structure known as the centrosome (centrioles) genetic material and the cell divides. duplicates itself to form two daughter centrosomes G1 phase. Metabolic changes prepare the cell for (centrioles) that migrate to opposite ends of the division. At a certain point - the restriction point - cell. the cell is committed to division and moves into the The centrosomes organize the production of S phase. microtubules that form the spindle fibres that S phase. DNA synthesis replicates the genetic constitute the mitotic spindle. material. Each chromosome now consists of two The chromosomes condense into compact sister chromatids. structures. Each replicated chromosome can now G2 phase. Metabolic changes assemble the be seen to consist of two identical chromatids (or cytoplasmic materials necessary for mitosis and sister chromatids) held together by a structure cytokinesis. known as the centromere. M phase. A nuclear division (mitosis) followed by a cell division (cytokinesis). PROMETAPHASE The period between mitotic divisions - that is, G1, S and G2 - is known as interphase. The chromosomes, led by their centromeres (centrioles), migrate to the equatorial plane in the MITOSIS mid-line of the cell - at right-angles to the axis formed by the centrosomes (centrioles). o Mitosis is a form of eukaryotic cell division that This region of the mitotic spindle is known as the produces two daughter cells with the same genetic metaphase plate. component as the parent cell. The spindle fibres bind to a structure associated o Chromosomes replicated during the S phase are with the centromere of each chromosome called a divided in such a way as to ensure that each kinetochore. daughter cell receives a copy of every Individual spindle fibres bind to a kinetochore chromosome. structure on each side of the centromere. The o In actively dividing animal cells, the whole process chromosomes continue to condense. takes about one hour. METAPHASE The chromosomes align themselves along the metaphase plate of the spindle apparatus.  ANAPHASE The shortest stage of mitosis. The centromeres divide, and the sister chromatids of each chromosome are pulled apart - or 'disjoin' - and move to the opposite ends of the cell, pulled by spindle fibres attached to the kinetochore regions. The separated sister chromatids are now referred to as daughter chromosomes. It is the alignment and separation in metaphase and anaphase that is important in ensuring that each daughter cell receives a copy of every chromosome. TELOPHASE The final stage of mitosis, and a reversal of many of the processes observed during prophase. The nuclear membrane reforms around the chromosomes grouped at either pole of the cell, the chromosomes uncoil and become diffuse, and the spindle fibres disappear. CYTOKINESIS The final cellular division to form two new cells. In plants a cell plate forms along the line of the metaphase plate; in animals there is a constriction of the cytoplasm. The cell then enters interphase - the interval between mitotic divisions.  ADDITIONAL INFORMATION TO REVIEW FOR PRELIM EXAM Watch this short video: https://youtu.be/f- mitosis, excessive cell growth, and the formation of ldPgEfAHI?si=iqyY2G7ghKvsoAs1 tumors, which can disrupt normal tissue function, consume vital nutrients, and metastasize to other parts of Watch this short video: the body. https://youtu.be/kQu6Yfrr6j0?si=DNaRpLqkqEGe QCwd 5. Compare and contrast the role of mitosis in unicellular and multicellular organisms. 1.How does mitosis contribute to both genetic stability and genetic variation in organisms? Answer: In unicellular organisms (e.g., bacteria, protists), mitosis is a form of asexual reproduction, allowing the Answer: Mitosis ensures genetic stability by producing organism to increase in population. In multicellular daughter cells that are genetically identical to the parent organisms, mitosis is used primarily for growth, cell, maintaining the same DNA sequence. However, development, repair, and maintenance of tissues, rather occasional errors such as mutations during DNA than reproduction. While both rely on mitosis for cell replication in interphase can introduce genetic variation. If division, the purpose differs significantly between the two these mutations occur in somatic cells, they may affect cell groups. function but are not inherited. 6. What would happen if a mutation disrupted the 2. What would be the consequences if spindle fibers regulation of the G2/M checkpoint in the cell cycle? failed to attach to one or more chromosomes during metaphase? Answer: If the G2/M checkpoint is disrupted, cells may enter mitosis with damaged or unreplicated DNA, leading Answer: If spindle fibers fail to attach to some to genomic instability. This increases the risk of mutations chromosomes, those chromosomes may not align properly accumulating, which can contribute to diseases such as at the metaphase plate and could be unequally distributed cancer, where abnormal cells continue dividing during anaphase. This could result in aneuploidy, where uncontrollably. one daughter cell receives extra chromosomes while another is missing some, potentially leading to diseases 7. How does mitotic failure lead to polyploidy in some like cancer or Down syndrome (if occurring in meiosis cells, and what are the consequences of polyploidy? instead). Answer: If a cell fails to complete cytokinesis after 3. How does mitosis ensure the maintenance of mitosis, it may retain multiple sets of chromosomes, chromosome number across cell generations? What leading to polyploidy (more than two sets of mechanisms are in place to prevent errors? chromosomes). In plants, polyploidy can be beneficial (e.g., larger fruit, increased stress tolerance), but in Answer: Mitosis maintains chromosome number by animals, it often results in lethal developmental defects. duplicating DNA during interphase (S phase) and equally distributing the sister chromatids during anaphase. 8. Why is apoptosis (programmed cell death) necessary Checkpoints in the cell cycle (G1, G2, and M phase in tissues where mitosis is highly active? checkpoints) help detect DNA damage, incomplete replication, or improper spindle attachment, preventing Answer: Apoptosis helps remove damaged, old, or faulty cell division and ensuring accurate chromosome excessive cells produced by mitosis, preventing tumor segregation. formation and ensuring tissue homeostasis. Without apoptosis, unchecked cell growth can lead to cancer or 4. Why do cancer cells often exhibit uncontrolled hyperplasia (excess tissue growth), disrupting normal mitosis, and how does this impact the body? function. Answer: Cancer cells bypass normal cell cycle regulation 9. If mitosis produces identical daughter cells, how do due to mutations in genes controlling cell division, such as specialized cells (e.g., neurons, muscle cells) arise from proto-oncogenes (which become oncogenes) or tumor mitotic divisions? suppressor genes (e.g., p53). This leads to uncontrolled Answer: Specialized cells arise through differentiation, which is controlled by gene expression rather than changes in DNA sequence. Even though mitotic daughter cells have identical DNA, external signals (hormones, growth factors) and internal regulators determine which genes are active, leading to different cell functions. 10. Why do some cells, such as nerve cells and cardiac muscle cells, enter G0 phase and rarely undergo mitosis? Answer: Cells in G0 phase are in a quiescent (non- dividing) state because they have completed their function and do not need constant renewal. Neurons and cardiac muscle cells are highly specialized and need to maintain long-term stability and function. If these cells were to divide uncontrollably, it could disrupt the nervous or circulatory system. However, limited regeneration can occur in certain cases.