Part II: Genetics – The basis of heredity

• FACT: Related individuals resemble each other more than randomly chosen individuals do

– Within populations

– Among populations within species

– Within species among species

– Etc.

…WHY??

Resemblance among relatives…”heredity”

• Information is passed from parent to offspring

• Information is passed largely intact

• That information encodes the phenotype

– Phenotype is any property of an organism that can be attributed to that organism (height, weight, eye color, obnoxiousness, etc.)

Outline of today’s lecture – (Ch. 12)

• Review of (some) Eukaryotic cell structures

• Schematic overview of mitosis

• The mitotic spindle

• Cytokinesis

• Cell cycle control

Review of Eukaryotic cell structures

• Nucleus

– Surrounded by membrane

– Contains the genetic material (DNA)

– During interphase, DNA uncoiled, complexed with proteins, called “chromatin”

– In mitosis, condenses into chromosomes

Review of Eukaryotic cell structures

• Nucleolus

– Point of synthesis of ribosomal RNA

– Ribosomal subunits assembled

Nucleolus

Review of Eukaryotic cell structures

• Centrosomes

– Region near nucleus that is the cellular “microtubule organizing center”

– Associated with formation of spindle fibers

– Form “spindle poles” during mitosis

Review of Eukaryotic cell structures

• Cytoskeleton

– Provides mechanical support to the cell

– Dynamic (disassemble and reassemble)

– Constructed of microtubules, microfilaments, intermediate filaments

Microtubules: Structure and Function

• Composed of polymers of dimers of α-tubulin, β-tubulin

• Lengthen by adding dimers, shorten by losing dimers

• “Molecular motors” can move along microtubules

Mitosis and the Cell Cycle

• All organisms must grow and reproduce

• During organismal growth, all cells must grow and divide

• Genetic information must be faithfully passed between parent cell and daughter cells

• MITOSIS is the process by which genetic information is passed from parent to daughter cells

The Cell Cycle – A schematic overview

Some notation

• Chromosome

• Centromere

• Spindle pole (centrosome)

• Spindle fiber

• Nuclear envelope

Schematic drawing of a chromosome

G1 (Interphase)

• Each chromosome is a single, unreplicated double strand of DNA

• One chromosome from each parent (Male, Female) forms a Homologous Pair (= “homologs”)

• Chromosomes in nucleus, surrounded by nuclear membrane

• Single centrosome

F

M

S-phase (DNA synthesis)

• After DNA replication, TWO “sister chromatids” are present for each homolog

• Each sister chromatid is the SAME double-stranded DNA molecule

• Attached by proteins, tightly at centromere and more loosely throughout their length

F

M

F

M

G2 (Interphase)

• Duplication of centrosomes

• Cell receives signal to enter mitosis F

M

F

M

M1 (Early Prophase)

• Chromosomes condense

• Mitotic spindle forms from centrosome

• Centrosomes begin to migrate to poles of cell

• Nucleoli disappear

FF

MM

M2 (Mid-prophase)

• Chromosomes fully condensed

• Centrosomes complete migration to the poles

• Nuclear envelope begins to degrade

• Spindle fibers enter nuclear area from the pole

• Kinetochores form at centromeres

FF

MM

M3 (Prometaphase)

• Nuclear envelope completely degraded

• Kinetochores form at centromeres

• Some spindle fibers attach at kinetochores

• Sister chromatids attached to opposite poles

FF

MM

M4 (Metaphase)

• Spindle fibers attached to centromere at kinetochore

• All sister chromatids attached to opposite poles

• Chromosomes migrate to center plane of cell, “metaphase plate”

FF MM

M5 (Early Anaphase)

• Protein bond between sister chromatids degrades

• Sister chromatids separate, begin migration toward opposite poles

• Poles move farther apart as non-kinetochore spindle fibers lengthen

M5 (Late Anaphase)

• Chromosomes (no longer “chromatids”) have reached poles

M6 (Telophase)

• Non-kinetochore spindle fibers continue to elongate cell

• Nuclear envelopes begin to form at poles

• Chromosomes de-condense back into chromatin

• Nucleoli re-form, cytokinesis begins

The mitotic spindle: Structure and Function

• Made of microtubules, associated proteins

• Cytoskeleton partially disassembles to provide materials

• Assembly starts in centrosomes

• Centrosomes “pushed” away from each other as microtubules grow

The mitotic spindle: Structure and Function

• Some spindle fibers grow and attach to the kinetochore while sister chromatids are still attached

• “Equilibrium” reached when sister chromatids are midway between the poles (metaphase plate)

Microtubules: Structure and Function

• Composed of polymers of dimers of α-tubulin, β-tubulin

• Lengthen by adding dimers, shorten by losing dimers

• “Molecular motors” can move along microtubules

The mitotic spindle: Structure and Function

• Hypothesized mechanism for chromosome movement

The mitotic spindle: Structure and Function

• Experimental Test of the hypothesized mechanism for chromosome movement

• What is an obvious alternative hypothesis?

Cytokinesis – Animal cells

• Cleavage furrow formed by contraction of a ring of microfilaments

• Associated with actin and myosin (motor protein system)

• Forms along metaphase plate

Cytokinesis – Plant cells

• Plants have cell walls

• Vesicles (derived from Golgi) move along microtubules to the middle of the cell

• Vesicles coalesce to form a “cell plate”; membrane derived from vesicles

• Cell plate membrane fuses with outer cell membrane, forms daughter cells

Cell Division in Prokaryotes - Binary fission

• Prokaryotes preceded Eukaryotes by billions of years

• Bacterial chromosome is circular DNA molecule

• Origin of replication

Cell Division in Prokaryotes - Binary fission

• As DNA replication proceeds, one copy of the origin migrates to each end of the cell

Cell Division in Prokaryotes - Binary fission

• Cell membrane grows inward

• New cell wall forms

• Two daughter cells result

• Migration of origin(s) is similar to migration of centromeres

Cell cycle - Regulation

• Timing and rate of cell division are critical

• Chemical signals regulate “checkpoints” in the cell cycle

• RESULTS of certain chemical processes are “checked”

• If results not appropriate, cell division does not proceed

• Evidence from cell fusion experiments

Cell cycle - Regulation

Cell cycle - Regulation

• G1 checkpoint: Cell will not enter into S phase unless appropriate signal is received– Many cells in adult mammals are in G0

and thus do not divide (e.g., nerve)

• If not, enters non-dividing “G0” phase

• Variety of external chemical cues to trigger entry into G1 and G2 phase (or not)

Cell cycle - Regulation

• Additional Regulatory Checkpoints

– Cell will not proceed through S-phase unless DNA synthesis completed

– M-checkpoint: Cell will not enter anaphase until chromosomes lined up on metaphase plate

Cell cycle - Regulation

• Cell cycle controlled by two types of proteins, kinases and cyclins

• Kinases active when attached to cyclins

• E.g., “Maturation-promoting factor” MPF

Molecular control of the cell cycle - MPF

Cell cycle regulation – internal and external controls

• M-checkpoint: if kinetochores not attached to spindle microtubules, sister chromatids remain attached

• G1-checkpoint: growth factors / receptors

– E.g., platelet-derived gf (PDGF), healing wounds

– Density-dependent inhibition (nutrient concentration below a certain level)

– Anchorage-dependence

For Wednesday: Ch. 13

• Meiosis

• Sexual Life Cycles