Biology 1216 Lecture Notes

Chapter 8 : Cellular Basis of Reproduction and Inheritance
Outline:

Cell division forms the basis for organismal reproduction and the growth and development from a single cell to a multicellular organism. In this chapter, two main types of cell division (mitosis and meiosis) and their functions in the organism are discussed.

Connections between cell division and reproduction

• It’s long been known that each kind of organism gives rise to its own kind (like-begets-like).
  
• In asexual reproduction offspring are genetically identical to each other as well as to their single parent. Asexual reproduction does not produce genetic variation.
  
  • before cells divide, chromosomes are duplicated, and identical chromosomes are allocated to opposite sides of the parent cell. When parent cell divides, each daughter cell receives a set of chromosomes identical to parent.
    
• In sexual reproduction, offspring are similar, but not identical to each other nor to both parents.
  
  • offspring inherit a unique combination of genes from two parents, resulting in genetic variation.
    
• 1858 Rudolf Virchow: all cells come from preexisting cells.
  
  • since all living things are cell-based, the perpetuation of life is based on cellular reproduction, a process commonly known as cell division.
    

Cell division in prokaryotes

• In prokaryotes genetic information is usually present in the form of a single chromosome.
  
  • DNA is circular (not linear as in eukaryotes), not as extensively associated with proteins, much shorter (therefore prokaryotes generally have far fewer genes), and not enclosed in a nucleus.
    
• Prokaryotes reproduce by binary fission (Fig 8.3).
  
  • as cell grows, it duplicates its DNA.
    
  • separation of chromosomes results from growth of new plasma membrane between 2 sites of membrane where chromosomes duplicates are attached.
    
  • Cell then pinches in two giving rise to 2 genetically identical cells.
    

Eukaryotic Cell Cycle and Mitosis

Chromosomes divide with each cell division

• Eukaryotic cells much more complex than prokaryotic cells
  
  • more DNA (more genes)
    
  • multiple linear chromosomes (46 in humans)
    
  • chromosomes extensively associated with proteins. These help organize DNA of chromosomes and control activity of genes.
    
• Chromosomes condense and become visible only just prior to cell division (Fig 8.4A).
  
  • rest of time, chromosomes present as chromatin, a diffuse mass of long fibers made of DNA and protein.
    
• Before cell division, chromosomes are duplicated (Fig 8.4B)
  
  • duplicates remain attached to each other at centromere. Each duplicate is called a sister chromatid. Sister chromatids are identical.
    
• When cell divides, sister chromatids separate, move to opposite poles of cell. When cell divides, each daughter cell receives a complete and identical set of chromosomes.
  

Cell Cycle

• Cell division forms basis of reproduction, growth from single cell to multicellular organism, and replacement of worn-out or damages cells.
  
• Eukaryotic cells that divide undergo a cell cycle (Fig 8.5).
  
  • cell cycle = orderly sequence of events that extends from time a cell divides to the time its daughter cells divide again.
    
• Cell cycle divided into 2 phases: Interphase and Mitotic phase.
  
• Interphase:
  
  • cells spend most of their time in this phase (~90%)
    
  • high metabolic activity; cell performs its various function.
    
  • Interphase divided into 3 subphases:
    
    • G1 (gap 1)
      
      • Cell increases its supply of proteins, organelles, and grows.
        
      • Most of interphase is spent in G1.
        
      • Cells that do not divide (e.g. muscle cells, neurons, etc…) are permanently arrested at G1.
        
    • S phase
      
      • DNA synthesis occurs; after S phase, each chromosome consists of two identical sister chromatids
        
    • G2 (gap 2)
      
      • Cell synthesizes proteins required for cell division.
        
• Mitotic phase
  
  • Divided into 2 parts: Mitosis (division of the nucleus), and cytokinesis (cytoplasm divides giving rise to two cells).
    
  • Mitosis is unique to eukaryotes; reflects an evolutionary solution to problem of partitioning large amount of genetic material to daughter cells.
    
  • Very accurate: error rate 1/100,000 cell divisions
    
  • Many visible changes in chromosomes and other structures
    

Mitosis

• Dynamic process in which duplicated chromosomes are separated from each other (nuclear division) followed by cell division.
  
• Typically divided into 4 stages: prophase, metaphase, anaphase, and telophase (Fig 8.6).
  
• Prophase
  
  • Chromatin fibers condense into discreet, easily seen chromosomes (made of 2 identical sister chromatids)
    
  • Nucleolus disappear
    
  • Mitotic spindle forms as microtubules grow out of centrosomes.
    
  • Centrosomes move away from each other.
    
  • In late prophase, nuclear membrane fragments and disappears.
    
  • Some spindle microtubules attach to kinetochores (1 per sister chromatid); others contact microtubules from opposite pole. Protein motors use force to move chromosomes to center of cell.
    
• Metaphase
  
  • Mitotic spindle at opposite ends of the cell
    
  • Chromosomes at center of cell with their centromeres placed at metaphase plate.
    
  • Kinetochore of each sister chromatid face opposite poles of spindle.
    
• Anaphase
  
  • Centromeres of each chromosome come apart, separating sister chromatids.
    
  • Separated sister chromatids now considered a “chromosome”
    
  • Movement of daughter chromosomes to opposite poles results from shortening of spindle microtubules attached to kinetochores
    
  • Non-kinetochore microtubules from opposite poles elongate and push against each other to elongate cell.
    
  • Anaphase is complete when each set of chromosomes at opposite poles.
    
• Telophase
  
  • Cell elongation continues
    
  • Nuclear membrane reappears
    
  • Chromosomes uncoil to form chromatin
    
  • Nucleoli reappear (sign of gene activity)
    
  • Mitotic spindle disappears
    
• Cytokinesis
  
  • Usually occurs while telophase in progress.
    
  • Involves division of cytoplasm (cell pinches in two), resulting in 2 identical cells, each with a nucleus and a complete set of chromosomes
    

Cytokinesis differs for plants and animals

• In animals, cytokinesis occurs by cleavage, resulting in cleavage furrow (shallow groove at cell surface) (Fig 8.7A)
  
  • cytoplasm has ring of microfilaments that contracts, pinching cell in two (like pulling a drawstring).
    
• In plants, vesicles migrate to middle of parent cell, fuse to form a membrane enclosed disk called cell plate. Plate grows outward, fuses with cell membrane resulting in two cells. Contents of vesicles will form new cell wall (Fig 8.7B).
  

Anchorage, cell density, and chemical growth factors affect cell division

• For multicellular organisms to develop normally, the timing of cell division in different parts of body must be controlled.
  
  • some cells divide more frequently than others: muscle and neurons do not divide in adults; liver cells replicate only to replace damage cells; cells in skin and those lining GI tract replicate continuously to replace lost cells .
    
• Much has been learned about control of cell division from cells grown in culture:
  
  • Anchorage dependence: animal cells divide only if in contact with solid surface
    
    • In animals, cell normally anchored to extracellular matrix or to other cells.
      
    • Keeps cells that may become separated from normal surroundings from dividing inappropriately.
      
  • Density-dependent inhibition: in culture, animal cells multiply to form monolayer, then stop when they touch each other. If some cells scraped out, adjacent cells divide and fill in gap
    
    • Results from inadequate supply of growth factors as population density increases. Addition of more growth factor, and cells continue to divide (although still form monolayer).
      
    • Important regulatory mechanism in body’s tissues to keep cell populations at optimal levels.
      
    • Growth factor = protein secreted by certain body cells that stimulates cells in vicinity to divide.
      

Regulation of cell cycle

• Normal cells in the body only divide when exposed to appropriate signals. These signals can be either from within the cell or from the outside and serve as cues to coordinate major events in the cell cycle.
  
• Cell cycle contains three critical checkpoints (G1, G2 and M checkpoints (Fig 8.9A), when stop and go-ahead signals can be applied to the cycle.
  
  • checkpoints are built-in molecular brakes that block cell cycle until overridden by goahead signals.
    
  • Intracellular signals detected by control system tell it whether key cellular processes have been completed and thus whether or not to proceed past that point.: e.g. cells are arrested at G1 phase until DNA has been repaired. When DNA is repaired, control system gets go-ahead signal at G1 checkpoint and cell soon enters S phase.
    
• Failure to control cell cycle may lead to uncontrollable cell division (i.e. cancer). Research into how cell cycle is regulated is leading into a better understanding into the nature of cancer.
  

Cancer

• Cancer is a genetic disease of the somatic tissue. Mutations to genes whose products regulate cell cycle and/or apoptosis results in uncontrollable cell proliferation.
  
• 20% of deaths in developed nations are due to cancer.
  
• Cancer cells have improperly functioning cell cycle control system. They divide excessively and invade other tissues in body.
  
• Tumor = mass of cells resulting from excessive growth.
  
• Benign tumor = mass of cells remains at original location (not invasive); can usually be surgically removed.
  
• Malignant tumor = cancerous; capable of spreading into neighboring tissues, displacing normal cells; cells often split from malignant tumor, invade lymph or circulatory system and spreads to other location in body where secondary tumors arise. This spread of cancer cells beyond original site is called metastasis.
  
• Cancers are named according to organ or tissue in which they originate:
  
  • Carcinomas = cancers that originate in external or internal linings of the body (i.e. epithelial tissue).
    
  • Sarcomas = cancers of tissues that support body (e.g. most connective tisse ) such as bone and muscle.
    
  • Leukemias and lymphomas = cancers of blood forming tissues (e.g. blood, bone marrow, spleen, lymph).
    
• Cancer treatment involves:
  
  • surgical removal of tumors (not always possible)
    
  • radiation and/or chemotherapy: both strategies target rapidly dividing cells.
    
• The superpowers of cancer
  
  • 1. Growth even in the absence of normal ”go” signals.
    
    • Most normal cells wait for an external message before dividing. Cancer cells often counterfeit their own pro-growth messages
      
  • 2. Growth despite “stop” commands issued by neighboring cells.
    
    • as tumor expands, it squeezes adjacent tissue, which sends out chemical messages that would normally bring cell division to a halt. Malignant cells ignore these commands.
      
  • 3. Evasion of built-in autodestruct mechanisms.
    
    • healthy cells activate a suicide program (apoptosis) when they suffer genetic damage beyond a critical level. Cancer cells can bypass this mechanism
      
  • 4. Ability to stimulate blood vessel construction.
    
    • tumors need oxygen and nutrients to survive. They obtain them by stimulating nearby vessels to form new branches that run throughout the growing mass.
      
  • 5. Effective immortality.
    
    • healthy cells can divide for no more than 70 times. Cancer cells can divide forever, partly because they can extend telomeres.
      
  • 6. Power to invade other tissues and spread to other organs (i.e. metastasis).
    
    • cancers usually become life threatening only after they disable cellular circuitry that confines them to a specific location.
      

Meiosis and Crossing Over

• In sexually reproducing organisms, offspring resemble their parents more than they do closely related individuals of same species. But offspring are not identical to their parents nor to their siblings. This section deals with how sexual reproduction passes chromosomes from parents to offspring.
  
• Sexual reproduction
  
  • results in much greater variation
    
  • two parents give rise to offspring that have unique combination of genes inherited from both parents
    
  • Offspring vary from their parents as well as their siblings.
    
  • Common in most multicellular organisms
    

Fertilization and meiosis alternate in sexual life cycles

• Life cycle = generation-to-generation sequence of stages in the reproductive history of an organism, from conception to reproduction of its own offspring.
  
• Somatic cells = any cell other than sperm and ovum. Human somatic cells have 46 chromosomes (23 pairs)
  
• Chromosomes can be distinguished by:
  
  • 1. size
    
  • 2. position of centromere
    
  • 3. staining pattern
    
• Karyotype = photographic display of number, forms, and types of chromosomes in a cell (Fig 8.19)
  
• Homologous chromosomes (homologues) = pair of chromosomes. These are identical in size, form, and in the genes they contain (may have different alleles). Each member of a pair is derived from each parent (Fig 8.12) .
  
• Sex chromosomes = 2 nonhomologous chromosomes which pair at meiosis. Determine sex. In humans, females are XX, males are XY.
  
• Autosomes = all other chromosomes.
  
• Each somatic cell in humans has 22 pairs of autosomes and 1 pair of sex chromosomes
  
• Gametes = sperm and egg cells (reproductive cells). Not produced by mitosis, but by meiosis. Haploid.
  
• Haploid (n) = contains only one set of chromosomes. For humans n = 23.
  
• Diploids (2n) = contain 2 sets of chromosomes. For humans, 2n = 46.
  
• Meiosis = type of cell division where chromosome number is reduced by half. Gives rise to reproductive cells. Allows for sexual reproduction.
  

Human life cycle

• Refer to fig 8.13
  
• Fusion of haploid gametes (egg and sperm) is called fertilization. Results in doubling of chromosome number in zygote.
  
• Zygote divides mitotically to produce diploid multicellular adult. In testes and ovaries, meiosis halves chromosome number to produce haploid gametes.
  
• Fertilization and meiosis offset each other to maintain chromosome number from generation to generation.
  
• All sexually reproducing organisms follow a basic pattern of alternation between haploid and haploid conditions.
  

Meiosis reduces the chromosomes number from diploid to haploid

• Meiosis, like mitosis, is preceded by chromosome replication.
  
• Meiosis involves 2 consecutive cell divisions, called meiosis I and meiosis II, resulting in 4 haploid daughter cells (Fig 8.14).
  Meiosis I
  
• segregates the two chromosomes of each homologous pair packaging them into separate daughter cells (i.e. centromeres do not divide).
  Meiosis II
  
• separates the two sister chromatids of each chromosome (centromeres divide).
  * NOTE: sister chromatids are identical to one another. Homologous chromosomes are not identical.
  

Comparison of mitosis and meiosis

• 3 main differences between mitosis and meiosis (all three differences unique to meiosis occur in meiosis I) (Fig 8.15).
  
  • 1. In prophase I homologues pair up, a process called synapsis. The four chromatids visible as tetrads. Chiasmata are visible manisfestation of crossing-over between non-sister chromatids. Neither synapsis nor chiasmata occur in mitosis.
    
  • 2. At metaphase I, pairs of chromosomes align at metaphase plate. In mitosis individual chromosomes align at metaphse plate.
    
  • 3. At anaphase I of meiosis, centromeres do not divide and sister chromatids do not separate, but remain attached and go to same pole of cell.Mechanisms of genetic variation during sexual reproduction
    

3 mechanisms contribute to genetic variation:

• 1. Independent assortment of chromosomes
  
  • orientation of homologous pair at metaphase I relative to the two poles is random (Fig 8.16).
    
  • each homologue has 50/50 chance of going to either pole.
    
  • number of combinations possible when meiosis packages chromosomes into gametes by independent assortment is 2n , where n is haploid number.
    
• 2. crossing over
  
  • during prophase I, crossing over occurs between portions of two nonsister chromatids (Fig 8.18).
    
  • in humans, average of 2 cross over events per chromosome.
    
• 3. random fertilization
  
  • each sex produces millions of different gametes (due to 1 and 2).
    
  • gametes fuse randomly, so total number of genetically distinct diploids is immense.
    

Nondisjunction alters chromosome number

• Alterations in chromosome number result from nondisjunction (pairs of chromosomes fail to separate at meiosis)(Fig 8.21)
  
• Aneuploidy = having + or - normal number chromosomes (monosomics vs trisomics).
  
• Chromosome deletions are usually lethal.
  
• Other chromosome aberrations may as lethal; some survive (e.g trisomy 21)
  
• Polyploidy = when organism has more than 2 complete sets of chromosomes. Originate by genome doubling. (haploid, diploid, triploid, tetraploid)
  
• Human disorders due to chromosomal alterations
  
  • Down syndrome; 1/700 children affected; extra chromosome 21; retardation to various drgrees; correlated with age of mother(Fig 8.20).
    
  • Trisomy 13; 1/500; rarely survive more than a year.
    
  • XXY males (Klinefelters syndrome): 1/2000; have male sex organs, but are abnormally small; breast enlargement and other female characteristics; normal intelligence.
    
  • XYY males; taller than average
    
  • XXX females; 1/1000; indistinguishable from XX
    
  • X females (Turner’s syndrome): 1/1000; phenotypically female but sex organs do not mature and are sterile.
    

Alterations of chromosome structure can cause birth defects and cancer

• Even if chromosome numbers are normal, abnormalities in chromosome structure cay cause disorders.
  
• Chromosome breakage can lead to a variety of rearrangements(Fig 8.23):
  
  • Deletions
    
  • Duplications
    
  • Inversions
    
  • reciprocal translocations
    
• some cancers result from chromosome abnormalities:
  
  • e.g. chronic myelogenous leukemia results from reciprocal translocation that activates a cancer gene (Philadelphia chromosome).

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