### Human Reproduction #### Male Reproductive System The male reproductive system includes primary sex organs (testes) and secondary sex organs (external genitalia, accessory ducts, and glands). **1. Primary Sex Organs: Testes** - Produce gametes (sperms) and sex hormones (androgens like testosterone). - Located in the scrotum, outside the abdominal cavity, to maintain a lower temperature (2-2.5°C lower than body temp) for spermatogenesis. **2. Accessory Ducts:** - **Rete Testis:** Network of tubules in the testis. - **Vasa Efferentia:** 10-20 small tubules connecting rete testis to epididymis. - **Epididymis:** Coiled tube (6m long) where sperm mature and are stored temporarily. Located on the posterior side of the testis. - **Vas Deferens:** Ascends to the abdomen, loops over the urinary bladder, and joins the duct from the seminal vesicle to form the ejaculatory duct. - **Ejaculatory Duct:** Formed by the union of vas deferens and seminal vesicle duct. - **Urethra:** Common passage for urine and semen (urinogenital duct). **Flowchart: Sperm Pathway** ``` Seminiferous Tubules → Rete Testis → Vasa Efferentia → Epididymis → Vas Deferens → Ejaculatory Duct → Urethra → Urethral Meatus ``` **Cross-section of Testis:** - **Testicular Lobules:** ~250 compartments in each testis. - **Seminiferous Tubules:** 1-3 highly coiled tubules within each lobule. Site of sperm production. - **Spermatogonia (Male Germ Cells):** Undergo meiosis to form sperm. - **Sertoli Cells:** Provide nutrition to developing sperm. - **Interstitial Spaces:** Regions outside seminiferous tubules. - **Leydig Cells (Interstitial Cells):** Produce androgens (male hormones). - **Immunocompetent Cells:** Immune cells. **3. Accessory Glands:** - **Seminal Vesicles (2):** Secrete fructose (energy for sperm), prostaglandins (motility), and clotting factors. Contribute 60-70% of semen volume. - **Prostate Gland (1):** Secretes a milky fluid containing calcium, citrate, and enzymes. Contributes 25-30% of semen volume. - **Bulbourethral Glands (2) (Cowper's Glands):** Secrete mucus for lubrication. Contribute 5-10% of semen volume. **Semen:** Mixture of sperm and secretions from accessory glands. Ejaculation volume: 2.5-5 mL, containing 200-300 million sperm. - 60% sperm with perfect shape and size, 40% vigorously motile. **4. External Genitalia:** - **Penis:** Erectile tissue, helps in insemination. - **Glans Penis:** Enlarged tip. - **Foreskin:** Loose fold of skin covering glans penis. - **Scrotum:** Pouch of skin that contains the testes. #### Female Reproductive System The female reproductive system includes primary sex organs (ovaries) and secondary sex organs (fallopian tubes, uterus, cervix, vagina, external genitalia, and accessory glands). **1. Primary Sex Organs: Ovaries** - Produce female gametes (ova) and steroid hormones (estrogen, progesterone). - Located in the pelvic cavity, one on each side of the uterus. - Each ovary is covered by a thin epithelium and contains ovarian follicles. **2. Accessory Ducts:** - **Fallopian Tubes (Oviducts) (10-12 cm long):** - **Infundibulum:** Funnel-shaped part closest to the ovary, with fimbriae (finger-like projections) to collect the ovum. - **Ampulla:** Wider part where fertilization usually occurs (ampullary-isthmic junction). - **Isthmus:** Narrow lumen, joins the uterus. - **Uterus (Womb):** Inverted pear-shaped, where fetal development occurs. - **Fundus:** Dome-shaped upper part. - **Body:** Main central part. - **Cervix:** Narrow opening into the vagina. - **Uterine Walls (3 layers):** - **Perimetrium:** External thin membranous layer. - **Myometrium:** Middle thick smooth muscle layer (strong contractions during childbirth). - **Endometrium:** Inner glandular layer (undergoes cyclical changes during menstrual cycle, site of implantation). - **Vagina:** Connects cervix to the exterior, part of the birth canal. **3. External Genitalia (Vulva):** - **Mons Pubis:** Cushion of fatty tissue covered by skin and pubic hair. - **Labia Majora:** Fleshy folds of tissue, extend down from mons pubis and surround vaginal opening. - **Labia Minora:** Paired folds of tissue under labia majora. - **Hymen:** Partial membrane covering vaginal opening, can be broken by various activities. - **Clitoris:** Tiny finger-like erectile tissue, homologous to the penis. **4. Accessory Glands:** - **Mammary Glands (Breasts):** Present in all female primates, contain glandular tissue and fat. - **Mammary Lobes (15-20 per breast):** Contain clusters of cells called alveoli. - **Alveoli:** Secrete milk, which is stored in the lumens. - **Mammary Tubules:** Alveoli open into these. - **Mammary Ducts:** Tubules join to form these. - **Mammary Ampulla:** Several mammary ducts join to form a wider ampulla. - **Lactiferous Duct:** Ampulla connects to this, through which milk is sucked out. - **Areola:** Pigmented area around the nipple. - **Milk Production & Ejection:** - **Prolactin:** Stimulates alveolar epithelial cells to produce milk. - **Oxytocin:** Stimulates myoepithelial cells for milk ejection. #### Gametogenesis Process of formation of gametes (sperm and ovum). **1. Spermatogenesis (Sperm formation in males):** - Begins at puberty and continues throughout life. - Occurs in seminiferous tubules. - **Spermatogonia (2n):** Undergo mitosis to increase in number. - **Primary Spermatocytes (2n):** Undergo Meiosis I to form two haploid secondary spermatocytes. - **Secondary Spermatocytes (n):** Undergo Meiosis II to form four haploid spermatids. - **Spermiogenesis:** Transformation of spermatids into spermatozoa (sperm). - **Spermiation:** Release of sperm from seminiferous tubules. **Hormonal Regulation of Spermatogenesis:** - **Hypothalamus:** Secretes Gonadotropin-Releasing Hormone (GnRH). - **Anterior Pituitary:** GnRH stimulates release of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH). - **LH:** Acts on Leydig cells to stimulate androgen (testosterone) production. - **FSH:** Acts on Sertoli cells to stimulate spermiogenesis. **Sperm Structure:** - **Head:** Contains nucleus (haploid) and acrosome. - **Acrosome:** Cap-like structure containing enzymes (e.g., hyaluronidase, acrosin) for fertilization. - **Neck:** Short region connecting head and middle piece. - **Middle Piece:** Contains mitochondria (for energy to swim). - **Tail:** Long, slender, for motility. - Covered by plasma membrane. - pH of sperm: 7.2-7.5. **2. Oogenesis (Ovum formation in females):** - Initiated during embryonic development (fetal life). - **Oogonia (2n):** Undergo mitosis to form primary oocytes. - **Primary Oocytes (2n):** Arrested in Prophase I of Meiosis I during fetal life. - At puberty, primary oocytes complete Meiosis I to form a large **Secondary Oocyte (n)** and a small **First Polar Body**. - Secondary oocyte arrests in Metaphase II. - Meiosis II is completed only upon sperm entry. If fertilization occurs, it forms a large **Ovum (n)** and a small **Second Polar Body**. **Ovarian Follicle Development:** - **Primordial Follicles:** Primary oocyte surrounded by granulosa cells. - **Primary Follicle:** Primary oocyte surrounded by more layers of granulosa cells. - **Secondary Follicle:** Contains an antrum (fluid-filled cavity). - **Tertiary Follicle:** Larger antrum, theca layers differentiate into theca interna and theca externa. - **Graafian Follicle:** Mature follicle, contains secondary oocyte. **Hormonal Regulation of Oogenesis:** - **Hypothalamus:** Secretes GnRH. - **Anterior Pituitary:** GnRH stimulates release of LH and FSH. - **FSH:** Stimulates follicular development and estrogen production by granulosa cells. - **LH:** Triggers ovulation (release of secondary oocyte) and corpus luteum formation. - **Estrogen:** Secreted by growing follicles, peaks just before ovulation. - **Progesterone:** Secreted by corpus luteum, maintains endometrium. #### Menstrual Cycle Cyclical changes in the endometrium and ovaries in sexually mature females, ~28 days. **Phases:** 1. **Menstrual Phase (Day 1-5):** - Endometrial lining sheds, causing bleeding. - Low estrogen and progesterone. - Follicular development initiated by FSH. 2. **Follicular/Proliferative Phase (Day 5-13):** - Endometrium regenerates. - Growing follicles secrete estrogen, which peaks around day 12-13. 3. **Ovulatory Phase (Day 14):** - LH surge (rapid increase in LH) triggers ovulation (release of secondary oocyte from Graafian follicle). - FSH also peaks. 4. **Luteal/Secretory Phase (Day 15-28):** - Ruptured follicle transforms into Corpus Luteum, which secretes progesterone and estrogen. - Endometrium thickens and becomes vascularized, preparing for implantation. - If no fertilization, corpus luteum degenerates, leading to a drop in hormones and onset of next menstrual phase. #### Fertilization and Implantation **1. Insemination:** Transfer of sperm into the female reproductive tract. **2. Capacitation:** Sperm acquire ability to fertilize. **3. Acrosomal Reaction:** Enzymes from acrosome (hyaluronidase, acrosin) break down layers of the ovum (corona radiata, zona pellucida). **4. Sperm Entry:** One sperm penetrates the ovum. **5. Cortical Reaction:** Prevents polyspermy. **6. Syngamy:** Fusion of sperm and ovum nuclei to form a diploid zygote. **7. Cleavage:** Rapid mitotic divisions of zygote. - **Morula:** 8-16 cell stage. - **Blastocyst:** Hollow ball of cells with an outer layer (trophoblast) and inner cell mass (ICM). **8. Implantation:** Blastocyst attaches to the endometrium of the uterus (around 7 days after fertilization). #### Pregnancy and Embryonic Development **1. Placenta Formation:** - Develops after implantation, connecting the developing embryo to the uterine wall. - **Functions:** Nutrient and oxygen supply, waste removal, hormone production (hCG, hPL, estrogen, progesterone, relaxin). **2. Embryonic Development (Gastrulation):** - Inner cell mass differentiates into three germ layers: Ectoderm, Mesoderm, Endoderm. **3. Parturition (Childbirth):** - Initiated by complex neuroendocrine mechanism (fetal ejection reflex). - Oxytocin causes strong uterine contractions. - Baby is pushed out, followed by the placenta. **4. Lactation:** - Milk production after childbirth. - **Colostrum:** First milk, rich in antibodies (IgA), essential for newborn immunity. ### Reproductive Health #### Population Explosion Rapid increase in population due to reduced death rates and increased birth rates. - **India's Initiatives:** - Family Planning Program (1951). - Reproductive and Child Health Care (RCH) program. - "Hum Do Hamare Do" (We Two, Our Two) slogan. - Promoting awareness about contraception and sex education. - **World Population:** 6 billion in 2000, 7 billion in 2011. India: 1 billion in 2000, 1.2 billion in 2011. - **Factors affecting population size:** Birth rate, death rate, Infant Mortality Rate (IMR), Maternal Mortality Rate (MMR), reproductive age group. - **Government measures for population control:** - Raising marriage age (females 18, males 21). - Incentives for smaller families. #### Contraceptive Methods Ideal contraceptive should be user-friendly, easily available, effective, reversible, with no side effects, and should not interfere with libido. **1. Natural Methods (Risky, No side effects):** - **Periodic Abstinence:** Avoiding coitus during the fertile period (days 10-17 of menstrual cycle). - **Withdrawal (Coitus Interruptus):** Male withdraws penis before ejaculation. - **Lactational Amenorrhea:** Absence of menstruation during intense breastfeeding (up to 6 months postpartum). **2. Barrier Methods:** - **Condoms:** Cover penis (male) or vagina/cervix (female). Prevent sperm and ovum meeting. Protect against STIs. Self-inserted. - **Diaphragms, Cervical Caps, Vaults:** Inserted into female reproductive tract. Cover cervix. Reusable. Do not protect against STIs. - **Spermicidal Creams, Jellies, Foams:** Used with barrier methods to increase effectiveness. **3. Intrauterine Devices (IUDs):** - Inserted by doctors/nurses into the uterus. Highly effective. - **Non-medicated IUDs:** Lippes Loop. - **Copper-releasing IUDs:** CuT, Cu7, Multiload 375. Suppress sperm motility and fertilizing capacity. - **Hormone-releasing IUDs:** Progestasert, LNG-20. Make uterus unsuitable for implantation and cervix hostile to sperm. **4. Oral Contraceptives (Pills):** - **Non-steroidal Pills:** Saheli (once a week pill), developed by CDRI, Lucknow. Blocks estrogen receptors, prevents implantation. - **Steroidal Pills:** Combination of progestogen and estrogen. Taken for 21 days, followed by a 7-day gap. Suppress ovulation and alter cervical mucus. **5. Implants:** - Progestogen-containing implants inserted under the skin. Release hormones slowly, making cervix hostile to sperm and inhibiting ovulation. **6. Emergency Contraceptives:** - Pills (high dose progestogen or progestogen-estrogen combination) or IUDs used within 72 hours of unprotected coitus to prevent pregnancy. **7. Surgical Methods (Terminal Methods):** - **Vasectomy (Males):** Vas deferens cut and tied, preventing sperm transport. - **Tubectomy (Females):** Fallopian tubes cut and tied, preventing ovum transport. #### Medical Termination of Pregnancy (MTP) Intentional or voluntary termination of pregnancy before full term. - Legalized in India (1971, amended 2017). - Safe up to 12 weeks (requires one doctor's opinion). - 12-24 weeks (requires two doctors' opinions, only if necessary). - Decreases maternal mortality. #### Sexually Transmitted Infections (STIs) Infections transmitted through sexual contact. - Common in age group 15-24 years. - **Bacterial:** Gonorrhea, Syphilis, Chlamydiasis (curable). - **Viral:** Genital Herpes, Hepatitis B, HIV/AIDS (not curable). - **Protozoan:** Trichomoniasis (curable). - **Symptoms:** Itching, fluid discharge, pain, swelling in genital region. Can lead to infertility, cancer if untreated. - **Prevention:** Avoid multiple partners, use condoms. #### Infertility Inability to conceive after 2 years of unprotected coitus. - **Assisted Reproductive Technologies (ART):** - **In Vitro Fertilization (IVF) (Test-tube baby):** Fertilization outside the body. - Zygote or early embryo (up to 8 blastomeres) transferred to fallopian tube (ZIFT). - Embryo (more than 8 blastomeres) transferred to uterus (IUT). - **Intracytoplasmic Sperm Injection (ICSI):** Sperm directly injected into ovum. - **In Vivo Fertilization:** - **Gamete Intra Fallopian Transfer (GIFT):** Ovum from donor inserted into fallopian tube of female who cannot produce ova. - **Artificial Insemination (AI):** Sperm from husband/donor artificially introduced into vagina/uterus. - **Adoption:** Legal method for childless couples. ### Biotechnology: Principles and Processes #### What is Biotechnology? - Integration of natural science and organisms, cells, parts thereof, and molecular analogues for products and services. - **Traditional Biotechnology:** Uses microbes for small-scale production (e.g., curd, bread, cheese). - **Modern Biotechnology:** Uses genetic engineering for large-scale production (e.g., insulin). - **European Federation of Biotechnology (EFB) Definition:** "The integration of natural science and organisms, cells, parts thereof, and molecular analogues for products and services." #### Principles of Biotechnology **1. Genetic Engineering:** Altering genetic material (DNA/RNA) to introduce desired genes into a host organism. **2. Bioprocess Engineering:** Maintaining sterile conditions for the growth of desired microbes/cells in large quantities for biotechnological products. **Advantages of Biotechnology:** - Preserves genetic information (in asexual reproduction). - Introduces variations (in sexual reproduction). - Can transfer desired genes without transferring undesirable ones. #### Tools of Recombinant DNA Technology **1. Enzymes:** - **Nucleases:** Cut nucleic acids. - **Exonucleases:** Remove nucleotides from ends. - **Endonucleases:** Cut at specific positions within DNA. - **Restriction Endonucleases:** "Molecular scissors." Recognize specific palindromic nucleotide sequences and cut DNA. - First discovered: Hind II (1972). - Over 900 restriction enzymes from 230 strains of bacteria. - **Nomenclature:** EcoRI (Eco: genus *Escherichia*, R: strain *RY13*, I: order of discovery). - Cut slightly away from the center of palindromic sites, creating "sticky ends" (single-stranded overhangs). - **DNA ligase:** "Molecular glue." Joins DNA fragments. - **DNA Polymerases:** Synthesize new DNA strands. **2. Cloning Vectors:** - DNA molecules that can carry a foreign DNA segment and replicate it inside a host cell. - **Features:** - **Origin of Replication (ori):** Sequence where replication starts. - **Selectable Marker:** Gene conferring resistance to antibiotics (e.g., ampicillin, tetracycline), helps identify transformants. - **Cloning Sites:** Recognition sites for restriction enzymes to insert foreign DNA. - **Examples:** - **Plasmids:** Extrachromosomal circular DNA in bacteria. - **pBR322:** Commonly used artificial plasmid vector. - **pUC8:** Plasmid vector with lacZ gene for blue-white selection. - **Bacteriophages:** Viruses that infect bacteria. - **Ti Plasmid (tumor-inducing plasmid):** From *Agrobacterium tumefaciens*. Used to deliver desired genes into plants. - **Retroviruses:** Used to deliver genes into animal cells. **3. Competent Host Cell:** - Host cells made capable of taking up foreign DNA (e.g., by treating with calcium ions and heat shock, or microinjection, gene gun). #### Process of Recombinant DNA Technology 1. **Isolation of Genetic Material (DNA):** - Cells are treated with enzymes (lysozyme for bacteria, cellulase for plant, chitinase for fungi) to break cell wall/membrane. - RNA and proteins removed by ribonucleases and proteases. - Chilled ethanol added to precipitate DNA ("spooling"). 2. **Cutting of DNA at Specific Locations:** - Restriction enzymes cut DNA into fragments. 3. **Separation and Isolation of DNA Fragments (Gel Electrophoresis):** - DNA fragments separated by size and charge using agarose gel. - DNA moves towards anode (positive electrode). Smaller fragments move faster. - DNA visualized under UV light after staining with ethidium bromide. - DNA fragments are cut out ("elution"). 4. **Amplification of Gene of Interest (PCR - Polymerase Chain Reaction):** - Multiple copies of desired DNA segment are made *in vitro*. - **Steps:** - **Denaturation:** DNA heated (94-96°C) to separate strands. - **Annealing:** Primers bind to complementary sequences on DNA strands (50-60°C). - **Extension:** DNA polymerase (Taq polymerase) synthesizes new DNA strands (72°C). 5. **Ligation of DNA Fragments into Vector:** - Desired DNA fragment and vector DNA are cut with the same restriction enzyme and ligated using DNA ligase. 6. **Insertion of Recombinant DNA into Host Cell (Transformation):** - Competent host cells take up the recombinant DNA. 7. **Selection and Screening of Recombinants:** - Identify host cells that have taken up the recombinant DNA using selectable markers (e.g., antibiotic resistance). - **Blue-white selection:** Differentiates between recombinant and non-recombinant colonies using the lacZ gene. 8. **Culturing Host Cells (Bioreactors):** - Recombinant host cells are grown in large-scale bioreactors (100-1000 liters) to produce the desired protein. - **Stirred-tank bioreactors:** Provide optimal conditions (temperature, pH, oxygen) for cell growth. 9. **Downstream Processing:** - Separation and purification of the desired protein product. - Quality control testing and preservation. ### Biotechnology and its Applications #### Therapeutic Applications **1. Genetically Engineered Insulin:** - Human insulin produced by recombinant DNA technology. - **Eli Lilly (1983):** Produced 'Humulin' by joining A and B chains from *E. coli* using disulfide bonds. **2. Gene Therapy:** - Correcting a defective gene responsible for a disease. - **Example:** ADA (Adenosine Deaminase) deficiency. - First treated (1990) in a 4-year-old girl. - Lymphocytes from patient are cultured, ADA gene introduced using retroviral vector, and then reinjected. - Not a permanent cure as lymphocytes have a limited lifespan. **3. Molecular Diagnostics:** - **PCR (Polymerase Chain Reaction):** Detects pathogens at low concentrations, early diagnosis of diseases (e.g., HIV, cancer). - **ELISA (Enzyme-Linked Immunosorbent Assay):** Detects antigens or antibodies for disease diagnosis. - **Autoradiography:** Detects gene mutations by using a radioactive probe. #### Transgenic Animals Animals with altered genetic material (foreign gene introduced). - **Examples:** Mice (95% of transgenic animals), sheep, cattle, rabbits, pigs, fish. - **Applications:** - **Study of Disease:** Model human diseases (e.g., cancer, cystic fibrosis) to develop new treatments. - **Normal Physiology and Development:** Study gene regulation and its effect on body functions. - **Vaccine Safety & Chemical Safety Testing:** Test safety of vaccines and chemicals. - **Biological Products:** - **Alpha-1-antitrypsin:** From transgenic sheep ('Tracy'), treats emphysema. - **Human alpha-lactalbumin:** From transgenic cow ('Rosie'), enriches milk for babies. #### Ethical Issues - **GEAC (Genetic Engineering Approval Committee):** Approves genetic research and products. - **Biopiracy:** Use of bio-resources without proper authorization or compensation (e.g., Basmati rice, Turmeric, Neem). ### Evolution #### Origin of Life - **Big Bang Theory:** Explains origin of universe (~20 billion years ago). - **Early Earth:** Formed ~4.5 billion years ago, hot, gases (H2, He) condensed. - **Life Origin:** First non-cellular life forms ~3 billion years ago, first cellular life forms ~2 billion years ago. - **Theories:** - **Theory of Special Creation:** Life created by divine power. - **Cosmozoic Theory (Panspermia):** Spores/seeds from outer space reached Earth. - **Theory of Spontaneous Generation:** Life arose from non-living matter (disproved by Louis Pasteur). - **Theory of Chemical Evolution (Oparin-Haldane):** Life arose from pre-existing non-living organic molecules. - **Miller's Experiment (1953):** Created amino acids *in vitro* using conditions simulating early Earth. #### Evidences for Evolution **1. Paleontological Evidence:** Fossils (remains of past life forms) show gradual changes over time. **2. Embryological Evidence:** Ernst Haeckel proposed that embryos of all vertebrates are similar, suggesting common ancestry (disproved by Karl Ernst von Baer). **3. Morphological and Anatomical Evidence:** - **Homologous Organs:** Similar structure, different function (e.g., forelimbs of whales, bats, cheetahs, human). Indicate divergent evolution. - **Analogous Organs:** Different structure, similar function (e.g., wings of insects and birds, eyes of octopus and mammals). Indicate convergent evolution. - **Adaptive Radiation:** Diversification of species from a common ancestor to adapt to different environments (e.g., Darwin's finches, Australian marsupials). #### Biological Evolution **1. Lamarck's Theory (Theory of Inheritance of Acquired Characters):** Use and disuse of organs leads to their development or degeneration, and these acquired characters are inherited (disproved). **2. Darwin's Theory (Natural Selection):** - **Observations:** Overproduction, limited resources, struggle for existence, variation. - **Key Concept:** Organisms with favorable variations survive and reproduce more ('survival of the fittest'). - **Reproductive Fitness:** Ability to produce more offspring. - **Branching Descent:** Different species arising from a common ancestor. - **Natural Selection:** Nature selects individuals with favorable variations. **3. Hugo de Vries (Mutation Theory):** Mutations are random and directional, cause 'saltation' (single step large mutation). **4. Modern Synthesis:** Combines Darwin's natural selection with genetics (mutations, genetic drift, gene flow). #### Mechanism of Evolution **1. Gene Flow:** Movement of genes between populations. **2. Genetic Drift:** Random changes in allele frequencies (e.g., bottleneck effect, founder effect). **3. Mutation:** Sudden heritable changes in DNA sequence. **4. Genetic Recombination:** Exchange of genetic material during meiosis. **5. Natural Selection:** Differential reproduction of individuals with favorable traits. **6. Hardy-Weinberg Principle:** Describes allele and genotype frequencies in a stable population. $p^2 + 2pq + q^2 = 1$. - **Factors affecting equilibrium:** Gene migration, genetic drift, mutation, genetic recombination, natural selection. #### A Brief Account of Evolution - **Non-cellular Life:** 3 billion years ago. - **Invertebrates:** 500 million years ago. - **Plants:** 400 million years ago. - **Fish:** 350 million years ago (lobed fins evolved into limbs). - **Amphibians:** Evolved from lobed-fin fish. - **Reptiles:** Dominated for ~200 million years (dinosaurs). - **Mammals:** Evolved from reptiles (first mammals were shrew-like). - **Human Evolution:** - **Dryopithecus & Ramapithecus:** Ape-like and man-like, ~15 million years ago. - **Australopithecus:** Hunted with stone weapons, ate fruit, ~2 million years ago. - **Homo habilis:** First human-like being, brain capacity 650-800 cc. - **Homo erectus:** Larger brain (900 cc), ate meat, ~1.5 million years ago. - **Neanderthal man:** Brain capacity 1400 cc, buried dead, ~100,000-40,000 years ago. - **Homo sapiens:** Modern humans, arose ~75,000-10,000 years ago. ### Molecular Basis of Inheritance #### The DNA - **Genetic Material:** Deoxyribonucleic acid (DNA). - **Structure:** Long polymer of deoxyribonucleotides. - **Deoxyribonucleotide:** Composed of a deoxyribose sugar, a nitrogenous base, and a phosphate group. - **Nitrogenous Bases:** - **Purines:** Adenine (A), Guanine (G) (double-ring). - **Pyrimidines:** Cytosine (C), Thymine (T) (single-ring). - **Phosphodiester Bonds:** Link nucleotides to form a polynucleotide chain (5' to 3' direction). - **Double Helix Model (Watson & Crick, 1953):** - Two polynucleotide strands, antiparallel (one 5'->3', other 3'->5'). - Sugar-phosphate backbone, bases project inwards. - Bases pair via hydrogen bonds: A with T (2 H-bonds), G with C (3 H-bonds). - Uniform diameter (20 Å), one turn (3.4 nm) contains 10 bp. - Right-handed coiling. - **Chargaff's Rule:** In dsDNA, A=T and G=C. - **DNA Packaging:** - **Prokaryotes:** DNA is supercoiled and associated with non-histone proteins. - **Eukaryotes:** DNA wrapped around positively charged histone proteins to form nucleosomes. - **Histones:** H1, H2A, H2B, H3, H4. (H2A, H2B, H3, H4 form octamer). - **Nucleosome:** DNA wrapped around histone octamer (200 bp DNA). - **Chromatin:** Loosely packed (euchromatin, transcriptionally active) and densely packed (heterochromatin, inactive). #### The Search for Genetic Material **1. Griffith's Transforming Principle (1928):** - **Experiment:** Heat-killed S strain (*Streptococcus pneumoniae*) transformed live R strain into S strain. - **Conclusion:** A "transforming principle" from S strain transferred to R strain. **2. Biochemical Characterization of Transforming Principle (Avery, MacLeod, McCarty, 1933-44):** - **Experiment:** Isolated biochemicals from S strain; only DNA caused transformation. - **Conclusion:** DNA is the genetic material. **3. Hershey-Chase Experiment (1952):** - **Experiment:** Used bacteriophages labeled with radioactive phosphorus (32P for DNA) and sulfur (35S for protein). - **Conclusion:** Only 32P (DNA) entered bacterial cells, proving DNA is the genetic material. #### RNA World and Replication **1. RNA as Genetic Material:** - Some viruses (e.g., Tobacco Mosaic Virus, HIV) have RNA as genetic material. - RNA is reactive and less stable than DNA. - RNA acts as genetic material, catalyst, and structural molecule. **2. DNA vs. RNA:** - **DNA:** More stable, deoxyribose sugar, thymine. - **RNA:** Less stable, ribose sugar, uracil. - DNA stores genetic information, RNA transmits it. **3. Central Dogma (Francis Crick):** DNA → RNA → Protein (unidirectional flow). - **Reverse Transcription:** In some viruses (retroviruses), RNA → DNA. **4. DNA Replication:** - **Semi-conservative (Watson & Crick):** Each new DNA molecule has one old and one new strand. - **Meselson-Stahl Experiment (1958):** Proved semi-conservative replication using heavy nitrogen (15N) in *E. coli*. - **Taylor's Experiment (1958):** Proved semi-conservative replication in eukaryotes (*Vicia faba*). - **Mechanism:** - **Origin of Replication (ori):** Specific sites where replication starts. - **DNA Helicase:** Unwinds DNA double helix. - **Replication Fork:** Y-shaped structure where DNA unwinds. - **DNA Polymerase:** Synthesizes new DNA strands (5'->3' direction). Highly efficient. - **DNA Primase:** Synthesizes RNA primers. - **Leading Strand:** Synthesized continuously. - **Lagging Strand:** Synthesized discontinuously in short fragments (Okazaki fragments). - **DNA Ligase:** Joins Okazaki fragments. - **Topoisomerase:** Relieves supercoiling. #### Transcription Process of synthesizing RNA from a DNA template. - Occurs in nucleus (eukaryotes) or cytoplasm (prokaryotes). - **RNA Polymerase:** Catalyzes RNA synthesis. - **Prokaryotes:** Single RNA polymerase for all types of RNA (mRNA, tRNA, rRNA). - **Eukaryotes:** RNA Pol I (rRNA), RNA Pol II (mRNA precursor - hnRNA), RNA Pol III (tRNA, 5s rRNA, snRNA). - **Transcription Unit:** DNA segment transcribed into RNA. - **Promoter:** Upstream region where RNA polymerase binds. - **Structural Gene:** Region transcribed into RNA. - **Terminator:** Downstream region where transcription ends. - **Mechanism:** - **Initiation:** RNA polymerase binds to promoter (with sigma factor in prokaryotes). - **Elongation:** RNA polymerase synthesizes RNA complementary to DNA template. - **Termination:** RNA polymerase detaches at terminator (with rho factor in prokaryotes). - **Features:** - **Triplet Codons:** Sequence of three nucleotides that code for an amino acid. - **Non-overlapping:** Codons do not overlap. - **Comma-less:** No punctuation between codons. - **Degenerate:** Some amino acids coded by more than one codon. - **Universal:** Same codons for same amino acids in most organisms. - **Start Codon:** AUG (codes for methionine). - **Stop Codons:** UAA, UAG, UGA (do not code for any amino acid). - **Split Genes (Eukaryotes):** Coding sequences (exons) interrupted by non-coding sequences (introns). - **RNA Processing (Eukaryotes):** - **hnRNA:** Heterogeneous nuclear RNA (precursor to mRNA). - **Capping:** Methyl guanosine triphosphate added to 5' end. - **Tailing:** Polyadenylation (200-300 adenine residues) added to 3' end. - **Splicing:** Introns removed and exons ligated together by spliceosomes. - **Mature mRNA:** Exons joined, ready for translation. #### Translation Process of synthesizing protein from mRNA. - Occurs on ribosomes. - **Components:** - **mRNA:** Carries genetic code. - **tRNA (Transfer RNA):** Adapter molecule, carries specific amino acids and has an anticodon loop that pairs with mRNA codons. - **rRNA (Ribosomal RNA):** Structural component of ribosomes, acts as a catalyst. - **Mechanism:** - **Aminoacylation:** Amino acid attaches to its specific tRNA. - **Initiation:** Ribosome binds to mRNA, initiator tRNA (carrying methionine) binds to start codon (AUG). - **Elongation:** tRNAs bring amino acids to ribosome, peptide bonds form between amino acids. - **Translocation:** Ribosome moves along mRNA. - **Termination:** Ribosome encounters stop codon, polypeptide chain released. #### Gene Regulation Control of gene expression. - **Prokaryotes:** Regulation primarily at transcription initiation. - **Lac Operon (*E. coli*):** Regulates metabolism of lactose. - **Components:** - **Regulatory Gene (i):** Codes for repressor protein. - **Promoter (p):** Binding site for RNA polymerase. - **Operator (o):** Binding site for repressor protein. - **Structural Genes (z, y, a):** Code for enzymes involved in lactose metabolism (β-galactosidase, permease, transacetylase). - **Repression:** Repressor protein binds to operator, preventing transcription. - **Induction:** Lactose (inducer) binds to repressor, inactivating it. Repressor detaches from operator, allowing transcription. - **Positive Regulation:** Inducer (lactose) promotes transcription. - **Negative Regulation:** Repressor protein inhibits transcription. #### Human Genome Project (HGP) International scientific research project to map and sequence the entire human genome. - **Goals:** - Sequence all 3 billion base pairs. - Identify all human genes. - Store information in databases. - Develop tools for data analysis. - Address ethical, legal, and social issues (ELSI). - **Methodologies:** - **Expressed Sequence Tags (ESTs):** Identify genes expressed as RNA. - **Sequence Annotation:** Sequence entire genome, then annotate coding and non-coding regions. - **Salient Features:** - ~3164.7 million bp. - ~30,000 genes. - Largest gene: Dystrophin. - Less than 2% of genome codes for proteins. - Repeated sequences make up large portion of genome. - Single Nucleotide Polymorphisms (SNPs): ~1.4 million locations. #### DNA Fingerprinting Technique to identify individuals based on unique DNA patterns. - Developed by Alec Jeffreys. - **Principle:** Uses repetitive DNA (satellite DNA) that shows high polymorphism. - **Steps:** 1. **DNA Isolation:** Extract DNA from sample. 2. **DNA Digestion:** Restriction enzymes cut DNA into fragments. 3. **Gel Electrophoresis:** Separate fragments by size. 4. **Southern Blotting:** Transfer DNA fragments to nylon/nitrocellulose membrane. 5. **Hybridization:** Labeled VNTR (Variable Number Tandem Repeats) probe binds to complementary sequences. 6. **Autoradiography:** Detect radioactive probe to visualize DNA fragments. - **Applications:** Forensic science, paternity testing, identification of individuals. ### Human Health and Disease #### Diseases Any condition that impairs normal functioning of the body. - **Types:** - **Infectious Diseases:** Transmitted from person to person (e.g., common cold, malaria, AIDS). - **Non-infectious Diseases:** Not transmitted (e.g., cancer, diabetes). **1. Bacterial Diseases:** - **Typhoid:** Caused by *Salmonella typhi*. Affects small intestine. Symptoms: sustained fever, loss of appetite, headache. Diagnosed by Widal test. - **Pneumonia:** Caused by *Streptococcus pneumoniae* and *Haemophilus influenzae*. Affects alveoli of lungs. Symptoms: fever, chills, cough, headache. - **Common Cold:** Caused by Rhinovirus. Affects nose and respiratory passage. Symptoms: nasal congestion, sore throat, cough. **2. Protozoan Diseases:** - **Malaria:** Caused by *Plasmodium* species (*P. vivax, P. falciparum, P. malariae*). Transmitted by *Anopheles* mosquito. Affects RBCs and liver. Symptoms: chills, high fever. - **Amoebiasis (Amoebic Dysentery):** Caused by *Entamoeba histolytica*. Affects large intestine. Symptoms: abdominal pain, cramps, constipation, blood in stools. **3. Helminthic Diseases:** - **Ascariasis:** Caused by *Ascaris lumbricoides* (roundworm). Affects intestine. Symptoms: internal bleeding, muscular pain, fever, anemia. - **Filariasis (Elephantiasis):** Caused by *Wuchereria bancrofti* or *W. malayi* (filarial worm). Affects lymphatic vessels, causes chronic inflammation and swelling of limbs/genitals. **4. Fungal Diseases:** - **Ringworm:** Caused by fungi (*Microsporum, Epidermophyton, Trichophyton*). Affects skin, nails, scalp. Symptoms: dry, scaly lesions, itching. **5. Viral Diseases:** - **AIDS (Acquired ImmunoDeficiency Syndrome):** Caused by HIV (Human Immunodeficiency Virus). Transmitted via sexual contact, infected blood, sharing needles, mother to child. Attacks immune system (T-helper cells). No cure. Diagnosed by ELISA. - **Cancer:** Uncontrolled cell growth. - **Types:** Benign (localized), Malignant (spreads - metastasis). - **Causes:** Carcinogens (physical, chemical, biological). - **Detection:** Biopsy, radiography (X-rays), CT scans, MRI. - **Treatment:** Surgery, radiotherapy, chemotherapy, immunotherapy. #### Immunity Ability of host to fight disease-causing organisms. - **Types:** - **Innate Immunity:** Non-specific, present from birth. - **Physical Barriers:** Skin, mucous membranes. - **Physiological Barriers:** Acid in stomach, saliva, tears. - **Cellular Barriers:** Phagocytes (neutrophils, macrophages). - **Cytokine Barriers:** Interferons. - **Acquired Immunity:** Specific, pathogen-specific, developed after birth. - **Primary Lymphoid Organs:** Bone marrow (B-cells) and thymus (T-cells) - site of lymphocyte development. - **Secondary Lymphoid Organs:** Spleen, lymph nodes, tonsils, Peyer's patches, appendix - site of immune response. - **Humoral Immunity:** Antibody-mediated, B-cells produce antibodies. - **Cell-mediated Immunity (CMI):** T-cell mediated. - **Antibody Structure:** Y-shaped, two heavy chains and two light chains, disulfide bonds. - **Vaccination & Immunization:** Generate immunity by exposing to weakened/inactivated pathogens. - **Allergy:** Exaggerated immune response to certain antigens (allergens). Mediated by IgE antibodies. - **Autoimmunity:** Immune system attacks self-cells. #### Adolescence and Drug/Alcohol Abuse - **Adolescence:** Period of transition from childhood to adulthood (12-18 years). - **Causes of Abuse:** Peer pressure, curiosity, stress, media influence. - **Drugs of Abuse:** - **Opioids:** Morphine, Heroin (diacetylmorphine). Depressants, pain killers. Derived from poppy plant (*Papaver somniferum*). - **Cannabinoids:** Marijuana, hashish, charas, ganja. Affect cardiovascular system. Derived from *Cannabis sativa*. - **Stimulants:** Cocaine (from coca plant *Erythroxylum coca*), Amphetamines. Increase alertness and energy. - **Hallucinogens:** LSD, Atropa belladonna, Datura. Alter thoughts, perceptions. - **Tobacco:** Nicotine stimulates adrenal gland, increases heart rate and blood pressure. Causes cancer, bronchitis, emphysema. - **Addiction:** Psychological attachment to effects of drugs/alcohol. - **Dependence:** Body needs regular doses, withdrawal symptoms if stopped. - **Prevention:** Education, counseling, seeking professional help. ### Ecology #### Organisms and Populations - **Ecology:** Study of interactions among organisms and between organisms and their physical environment. - **Levels of Organization:** Organism → Population → Community → Ecosystem → Biome → Biosphere. - **Population:** Group of individuals of the same species living in a geographical area, interbreeding. - **Population Attributes:** - **Birth Rate (Natality):** Number of births per unit population per unit time. - **Death Rate (Mortality):** Number of deaths per unit population per unit time. - **Sex Ratio:** Number of females per 1000 males. - **Age Distribution:** Proportion of individuals in different age groups (pre-reproductive, reproductive, post-reproductive). - **Population Growth Models:** - **Exponential Growth:** Occurs when resources are unlimited. J-shaped curve. $dN/dt = rN$. - **Logistic Growth:** Occurs when resources are limited. S-shaped curve. $dN/dt = rN(K-N)/K$. $K =$ carrying capacity. - **Population Interactions:** - **Mutualism (+/+):** Both species benefit (e.g., lichens, mycorrhizae, fig & wasp). - **Competition (-/-):** Both species harmed (e.g., interspecific competition). - **Predation (+/-):** Predator benefits, prey harmed (e.g., tiger & deer). - **Parasitism (+/-):** Parasite benefits, host harmed (e.g., human liver fluke, ticks). - **Commensalism (+/0):** One benefits, other unaffected (e.g., orchid on mango tree, barnacles on whale). - **Amensalism (-/0):** One harmed, other unaffected (e.g., penicillin & bacteria, goat & beetle). #### Ecosystem Structural and functional unit of nature where living organisms interact among themselves and with the surrounding physical environment. - **Components:** Biotic (living) and Abiotic (non-living). - **Functions:** - **Productivity:** Rate of biomass production. - **Gross Primary Productivity (GPP):** Total biomass produced. - **Net Primary Productivity (NPP):** GPP - Respiration. - **Decomposition:** Breakdown of complex organic matter into simpler inorganic substances. - **Steps:** Fragmentation, Leaching, Catabolism, Humification, Mineralization. - **Energy Flow:** Unidirectional flow of energy from sun to producers to consumers. - **10% Law (Lindeman):** Only 10% of energy transferred to next trophic level. - **Food Chain:** Linear sequence of who eats whom. - **Food Web:** Interconnected food chains. - **Nutrient Cycling:** Movement of nutrients through ecosystem. #### Biodiversity and Conservation - **Biodiversity:** Variety of life forms on Earth. - **Levels:** - **Genetic Diversity:** Variation within a species (e.g., *Rauwolfia serpentina*). - **Species Diversity:** Variety of species in an area (e.g., Western Ghats amphibians). - **Ecological Diversity:** Variety of ecosystems (e.g., deserts, rainforests, mangroves). - **Patterns of Biodiversity:** - **Latitudinal Gradients:** Biodiversity decreases from equator to poles. - **Species-Area Relationship:** Species richness increases with increasing area, up to a limit. - **Importance of Biodiversity:** - Ecosystem stability and resilience. - Provides ecological services (oxygen, pollination). - Source of food, medicines, industrial products. - **Loss of Biodiversity:** - **Causes (The "Evil Quartet"):** - **Habitat Loss and Fragmentation:** Destruction of natural habitats. - **Over-exploitation:** Overuse of resources. - **Alien Species Invasions:** Introduction of non-native species harming native ones (e.g., Nile perch, *Lantana*). - **Co-extinctions:** Loss of one species leading to loss of another. - **Conservation:** - **In situ Conservation:** Protecting species in their natural habitats. - **Biodiversity Hotspots:** Regions with high endemism and threat (34 worldwide, 3 in India: Western Ghats & Sri Lanka, Indo-Burma, Himalayas). - **National Parks, Wildlife Sanctuaries, Biosphere Reserves, Sacred Groves.** - **Ex situ Conservation:** Protecting species outside their natural habitats. - **Zoological Parks, Botanical Gardens, Wildlife Safaris.** - **Cryopreservation:** Storing gametes/embryos at low temperatures. - **Seed Banks.** - **Conventions:** - **Earth Summit (Rio de Janeiro, 1992):** Sustainable use of biodiversity. - **World Summit (Johannesburg, 2002):** Commitment to reduce biodiversity loss.