Mitosis and Meiosis: Cell Division

• There are two types of cell division: mitosis and meiosis.

Mitosis

• Occurs in somatic cells (not sex cells or neurons)
• Results in two genetically identical diploid body cells
• Important for growth and repair
• Diploid cells have two sets of chromosomes (2N)

Meiosis

• Occurs in sex cells
• Results in genetically different haploid gametes (sperm and egg)
• Haploid cells have one set of chromosomes (1N)
• Haploid + haploid = diploid

Chromosomes

• Must be replicated before cell division

DNA Replication

• Creates two identical cells
• DNA is duplicated during the S phase
• Results in two exact copies (sister chromatids) held together by a centromere
• One copy goes into each new cell

Semi-Conservative DNA Replication

• Each new double-stranded molecule has one original (parent) strand and one new (daughter) strand
• DNA must be exactly copied (replicated) before both mitosis and meiosis (cell division) during the "S" phase of interphase.

Origin of Replication

• Where DNA replication starts

Chromosome Structure

• Chromosomes are tightly coiled DNA molecules with histones (DNA + Histones)
• Chromosomes carry the code for our bodies (i.e., traits)
• Humans have 23 pairs of chromosomes
• Autosomes are chromosomes #1-#22
• The sex chromosome is #23
• Chromatin is an un-condensed chromosome (present during Interphase)
• A chromatid is one of a pair of replicated chromosomes
• A centromere holds together sister chromatids
• Sister chromatids are two identical chromatids held together by a centromere
• Condensed DNA forms the chromosome
• Histones help the DNA condense

The Cell Cycle

• Mitosis is a part of the cell cycle
• During the cell cycle (except mitosis), eukaryotic chromosomes are uncoiled and spread out
• After replication, each chromosome appears as two identical DNA molecules held together at the centromere
• Each DNA molecule is called a chromatid; together, the two are called sister chromatids until the centromere separates.

Mitosis Phases

• Prophase: Nuclear membrane breaks down, sister chromatids condense, and the spindle forms from the cytoskeleton
• Metaphase: Sister chromatids line up at the center of the cell
• Anaphase: Sister chromatid pairs are pulled apart by the spindle fibers; one set of chromosomes goes to each side of the cell
• Telophase: Chromosomes begin to uncoil, the nuclear membrane reassembles, and cytokinesis starts
• Cytokinesis divides the cytoplasm into two daughter cells, physically separating cells

Mitosis Outcomes

• Results in genetically identical diploid cells
• Occurs in four phases: prophase, metaphase, anaphase, telophase, and cytokinesis
• Advantages: Heals injury (fast recovery from burn)
• Disadvantages: Cancer What would happen if all of our cells reproduced EXACTLY? Everyone in the world would be exactly the same

Sexual Reproduction

• Alternates between diploid (2N) and haploid (1N) states

Meiosis

• Gives rise to haploid gametes
• In females occurs in ovaries and produces eggs
• In males occurs in testes and produces sperm

Additional Terms

• Gametes are haploids found in sex cells
• Somatic cells are diploids found everywhere except sex cells and neurons
• A homologous pair is two pairs of the exact same chromosomes
• A homologous chromosome is replicated and joined by a centromere and will split into other cells
• Sister chromatids are joined by a centromere
• Gene: a segment of DNA that codes for a protein
• Locus: location, where the gene is found
• Allele: An alternative form of a trait (Ex. tall or short)

Mitosis vs. Meiosis

Mitosis

• One round of replication
• One round of division
• Sister chromatids separate
• Result: Diploid cells, two identical daughter cells

Meiosis

• One round of replication
• Two rounds of division (Meiosis 1 and 2)
• Homologous PAIRS separate
• Result: Haploid cells, four genetically different daughter cells (gametes)

Spermatogenesis and Oogenesis

• Meiosis in humans

Stem Cells

• Can be grown into any type of cell needed under the right conditions
• Can be genetically altered to correct defects
• Clonal technology can be applied NIH Stem Cell Basics Unspecialized cells
• Totipotent: Can become any cell type, including placental cells
• Pluripotent: Can become any cell type in the body, but not placental cells
• Multipotent: Can develop into a limited number of cell types

Sources of Human Stem cells

Native Sources

• Embryonic stem cells are the least differentiated and hold the most promise
• Adult stem cells hold promise but often have already started differentiation down a specific path
• Umbilical stem cells are plentiful but mostly effective for producing blood cells

The Lab

• Creating embryonic stem cells from somatic cell nuclear transfer (induced pluripotent stem cells)
• Cloning technology

Potential Used for Stem Cells

Non-Controversial

• Therapeutic cloning
• Regeneration of tissues
• Treatment of cancers
• Testing new drugs

Controversial

• Reproductive cloning
• 1996 - Dolly the Sheep
• 2014 - A business
• Cloning cats and dogs is expensive and controversial. Humans behind petfluencer account say it is worth it

DNA

• DNA codes for our genes to create proteins
• A - T, G - C

Semi-Conservative DNA Replication

• Each new double-stranded molecule has one original (parent) strand and one new (daughter) strand DNA must be exactly copied (replicated) before both mitosis and meiosis (cell division) during the “S” phase of interphase.

Types of RNA Involved in Protein Synthesis

• Messenger RNA (mRNA): Coded instructions for protein synthesis (CODONS)
• Ribosomal RNA (rRNA): Part of the ribosome
• Transfer RNA (tRNA): Carries specific amino acids to ribosomes to be added to polypeptide chain (ANTICODON)
• Transcription and DNA replication are NOT the same. Transcription makes RNA; Replication makes DNA*

Protein Synthesis

• DNA is The Blueprint For Protein Synthesis

Central Dogma

DNA -> RNA -> Protein:

• DNA code is held in the nucleus
• DNA is TRANSCRIBED TO RNA (**NOT DNA REPLICATION!!!)
• After editing, RNA leaves the nucleus and takes directions to the ribosome
• mRNA is TRANSLATED into protein
• Protein is the foundation of traits
• Controlling this process is gene regulation

Transcription

DNA -> RNA (Nucleus):

• DNA Bases = A, T, G, C
• RNA Bases = A, U, G, C

mRNA Modification

• Introns = removed from the primary transcript
• Exons = spliced together
• After processing, mRNA is transported to the ribosome

The "Code" Is Read From The RNA In Codons:

• Codon: 3 BP “Words” in the genetic code
• A three-base sequence that translates into one amino acid
• Example: UUC on mRNA specifies the amino acid phenylalanine
• Codons “code” for an amino acid (ex. ACU, UAA, CAU, CUA, GUA)

Translation

RNA -> Protein (Cytoplasm at Ribosome): Protein Synthesis:

• Anticodon:
• A three-base sequence on the tRNA that is complementary to the mRNA codon
• tRNA recognizes both the codon on mRNA and the amino acid specified by the codon
• Brings amino acid to the “complementary MATCH” on the mRNA

Examples

DNA -> RNA -> Protein

• DNA: GAT - GCA
• mRNA (Codon): CUA - CGU
• tRNA (Anticodon): GAU - GCA

Mutations

Ex: ATG, TCA, ATC -> ATG, CAA, TC_

• Silent mutation: change in the coding, but the amino acid is still coded the same
• Insertion: new letter
• Deletion: removal of a letter

COVID and Mutations

• BA. 1 (-)
• BA. 2 (_)
• BA. 5… (/)

DNA and Biotechnology

• Biotechnology is the use of technology to modify organisms, cells, and their molecules for the betterment of the human condition
• Results in faster growth and bigger bodies

DNA Technologies

• Recombinant DNA: Novel genetic makeup using two sources of DNA
• Polymerase Chain Reaction (PCR): A way of making multiple copies of DNA
• Gel Electrophoresis/DNA Fingerprinting: A way of using small differences in an individual’s DNA (STR) to identify individuals, trace relatedness, solve crimes
• CRISPR: Editing genes

Important Biotechnology Applications

• CHOP: Isolate a gene of interest using restriction enzymes
• Amplify (multiply): Polymerase Chain Reaction (PCR)
• Insert: Use plasmids to transfer DNA from one organism to another
• Grow: Creating a gene library

Genetic Testing

• Screen for specific gene products
• Screen for changes in known gene sequences
• Probe for known abnormal sequences
• Currently, it can screen for ~900 genetic abnormalities

Screening

• Alzheimer’s Disease
• Inherited Breast and Ovarian Cancer
• Hereditary Nonpolyposis Colon Cancer
• Cystic Fibrosis
• Duchenne Muscular Dystrophy/ Becker Muscular Dystrophy
• Hemophilia A and B
• Hereditary Hemochromatosis
• Huntington’s Disease
• Phenylketonuria
• Sickle Cell Disease
• Tay-Sachs Disease

Gene Therapy

• Put functional genes into body cells affected by defective (mutant) gene
• Viruses are used to deliver a healthy gene
• A potential cure for inherited diseases
• Has had some success with severe combined immunodeficiency disease (SCID)
• Has had limited but promising small trials in Hemophilia, cancers, Sickle Cells, hereditary blindness

The Human Genome Project and ENCODE

• ENCYCLOPEDIA OF DNA ELEMENTS
• Each chromosome = a long twisted molecule of DNA
• 3-3.5 BILLION base pairs
• Only 20-25,000 GENES
• LESS THAN 2% codes for proteins
• ENCODE - figuring out what each does
• Epigenetics - Study of what turns genes on and off
• Gel Electrophoresis

CRISPR

• Clustered Regularly Interspaced Short Palindromic Repeats
• System for editing DNA with a great deal of precision and efficiency
• Enables researchers to modify almost any gene in any organism
• Naturally occurs in almost half of all bacteria as a mechanism for recording encounters with viral DNA and using information to protect against future infections

What makes CRISPR so powerful?

• With CRISPR technology, beagles have been engineered to be born with twice as much muscle as a typical dog
• Editing stem cell genomes could help treat many disorders, but DNA damage in CRISPR-edited cells might increase cancer risk
• Mosquito DNA can be altered to block malaria from spreading

The Risks of CRISPR

• Legal issues surrounding who has the rights to develop and profit from it
• Ethical Issues
• Potential for editing human embryos
• Potential for editing germline cells (sperm and eggs)
• Difficulty in predicting consequences of introducing altered genes into genomes of natural populations

DNA components

• Phosphate, sugar, base

Reproduction And Development

• Anatomy and Physiology
• Fertilization and Pregnancy
• Contraception

The Male Anatomy

• Urinary Bladder
• Ureter
• Vas deferens: Transports sperm from the epididymis to the urethra. Conducts sperm from the epididymis to the urethra
• Seminal vesicle: Produces fluid that nourishes sperm, thickens semen, and assists sperm movement
• Prostate gland: Produces alkaline secretions that activate sperm and reduce acidity in the reproductive system. Produces secretions that make sperm mobile and counteract the acidity of the female reproductive tract.
• Bulbourethral gland: Produces mucus secretion before ejaculation to neutralize acidic urine
• Erectile tissue of the penis: Fills with blood during arousal, causing erection
• Urethra: Transports semen during ejaculation and urine at other times. Tube through which sperm or urine leaves the body.
• Testis: Produces sperm and testosterone. Cremaster muscle raises the testes to bring it closer to the body when the testes need to warm and relax to create distance between the testes and the body in order to cool the testes.
• Penis: Delivers sperm to the female reproductive tract
• Glans penis: Rich in sensory nerves for sexual arousal
• Epididymis: Stores sperm and allows them to mature
• Uncoiled seminiferous tubules

The Male Physiology

• Gametogenesis:
• Gametes are haploid (n) and contain 23 chromosomes
• Gamete formation involves meiosis
• Meiosis reduces chromosomes from 2n to n
• One round of DNA replication and two rounds of cell division (meiosis 1 and 2)
• Produces four different gametes
• Spermatogenesis is the formation of sperm

Diploid

• Spermatogonium: two copies of each chromosome
• Primary spermatocyte

Haploid

• Secondary spermatocyte: one copy of each chromosome
• Later spermatids
• Spermatozoon

Hormones In Male Reproduction

• Testosterone: Sperm production, development/maintenance of reproductive structures, secondary sex characteristics, sex drive
• Gonadotropin-releasing hormone (GnRH): Stimulates the anterior pituitary gland to release LH
• Luteinizing hormone (LH): Stimulates interstitial cells of the testis to produce testosterone
• Follicle-stimulating hormone (FSH): Enhances sperm formation
• Inhibin: Inhibits FSH secretion, decreasing sperm and testosterone production
• Allele = alternative form of a trait

Ploidy Number

• Spermatids are haploid, so n
• Spermatogonia are diploid, so 2n
• Spermatozoan are haploid, so n

The Female Anatomy

• Uterus: Houses and nourishes the developing baby. Receives and nourishes the embryo.
• Uterine Wall: Muscle layers that stretch and contract during childbirth
• Endometrium: Uterine lining that changes monthly
• Cervix: Opening of the uterus that extends into the vagina
• Rectum
• Vagina: Receives the penis during sexual intercourse/serves as birth canal
• Oviduct: Conducts the egg toward the uterus /site of fertilization
• Ovary: Produces eggs and sex hormones

Other Female Anatomy

• Urinary Bladder
• Urethra
• Clitoris: Contributes to sexual arousal
• Labium minor: Inner skin folds
• Labium majora: Outer skin folds
• Breasts: Produce milk
• Pigmented Areola surrounding the nipple contains sebaceous glands to prevent nipples from drying out
• Milk production-milk glands
• Breast Cancer: 2nd leading cause of death in women

The Female Physiology

• Gametogenesis:
• Gamete formation:
• Meiosis reduces chromosomes from 2n to n
• One round of DNA replication and two rounds of cell division (meiosis 1 and 2)
• Produces 1 functional gamete
• Oogenesis is the formation of eggs

Diploid

• Primary oocyte: arrested in prophase 1 present at birth
• Primary oocyte: still arrested in prophase 1

Haploid

• Meiosis 2 completed: only if sperm penetrates the oocyte

Hormones In Female Reproduction

• Estrogen: Maturation of the egg, development/maintenance of reproductive structures, secondary sex characteristics, thickens endometrium, cell division in breast tissue
• Progesterone: Prepares the uterus for implantation and maintains the endometrium
• Follicle-stimulating hormone (FSH): Stimulates the development of a follicle in the ovary
• Luteinizing hormone (LH): Triggers ovulation and causes the formation of the corpus luteum

Fertilization

• Involves the acrosomal reaction and sperm penetration

Pregnancy Facts

• Recommended weight gain during pregnancy ~27lbs
• 7.5lbs baby
• 5lbs placenta
• 3lbs uterus
• 6.5lbs fluid
• 5lbs maternal fat
• Maternal blood volume increases 20-40% with no additional RBC count
• Your 17yds of skin stretches to 18-19yds by the end of pregnancy

Contraception Methods

• Abstinence
• Hormone-containing skin patch
• Vaginal contraceptive ring
• Intrauterine device (IUD)
• Diaphragm
• Cervical cap
• Spermicidal cream or jelly
• Male latex condom
• Female polyurethane condom
• Hormone Injection
• Oral contraceptive
• “Morning After Pill”
• Combined estrogen and progesterone
• Progesterone only
• Fertility awareness (abstinence on days that eggs and sperm may meet)
• Sterilization
• Vasectomy (Vas Deferens
• Tubal Ligation
• Tie and Cut (Fallopian Tubes)
• Cauterized (Fallopian Tubes)
• Banded (Fallopian Tubes)

STDs/STIs

• Chlamydial Infections: Genital discharge, itching, painful urination; treat with antibiotics
• Gonorrhea: Genital discharge, painful urination; treat with antibiotics
• Syphilis: Ulcer on genitalia in early stages; treat with antibiotics (early stages)
• Genital Herpes: Recurring blisters on genitalia; treat with Valacyclovir to prevent recurrences
• Genital Warts: Painless growths on genitalia; treatment involves removal
• AIDS and HIV Infections: Weakens immune system; treat with a combination of drugs
• Trichomoniasis: Vaginal irritation, itching, and discharge; treat with antiprotozoal drugs
• Candidiasis: Similar to trichomoniasis; treat with antifungal drugs