5 Cancer and Introduction to Evolution

cell division

cell division

• Unicellular organisms reproduce by __

• Required in multicellular organisms for tissues to grow and repair.

• Depends on intrinsic and extrinsic factors:

  • Is the cell ready?

  • Does the environment support growth?

cyclins

• Important because Cyclin Dependent Kinases (Cdks) must bind to __ in order to be active

• Abundant and present only when their Cdks need to act. __ are regulated at the RNA level and at the protein level.

cdks/cyclin dependent kinsases

• Add phosphates to downstream targets, which turns some targets on and some off. This drives the cell to progress through the cell cycle. Different __ are needed for different cell cycle phases.

• Regulated by:

  • The availability of Cyclins to partner with

  • The phosphorylation state of the __ themselves

  • __-inhibitors

cell cycle checkpoints

• Regulate cyclin-Cdk activity

• If a cell cannot pass a __ (e.g. if DNA damage is irreparable or if required growth factors are not present), the cell dies by apoptosis.

apoptosis

programmed cell death, occurs

• After many cell divisions

• In the absence of growth signals

• In response to viral infection or trauma

process:

• DNA condenses and fragments

• Proteases digest proteins

• Oxidative bursts kill cell from within

• Apoptosis requires transcription and translation

mitosis

cell division

• Microtubules segregate the chromosomes. Actin helps separate the two daughter cells.

growth factors

• Signals that:

  • Encourage cells to increase in size

  • Encourage cells to survive

  • Encourage cells to divide

• Released into a cell’s environment to regulate the cell cycle. This is especially important during the G1-S transition.

• Cells respond to __ in complex ways, including progressing from G1 to S. This requires activation of a transcription factor (E2F) that turns on genes required for copying the chromosomes.

RAS

• Downstream of certain growth factor receptors.

  • Growth factor → receptor → __ → Mitosis

• __ is a GTPase: after a short time it shuts itself off

• __ without GTPase activity cannot shut itself off

• Activated __ (like activated receptor) → cancer

malignancy

shared traits with cancer:

• Independence from external and internal growth signals

• Defects in apoptosis (programmed cell death)

• Continue to divide indefinitely

• Genetically unstable

cancer

a disease of genetics and development

• invasive

• metastasize

strategies:

• Produce growth factor themselves

• Stimulate normal cells to secrete growth factor

• Increase levels of growth factor receptors at cancer cell surface

• Gain-of-function mutation in growth signaling pathway

evolution

theories:

• A hypothesis is a specific idea or model that can be tested by scientific experiments (e.g. growing a plant in shade will result in stunted growth).

• A law is a scientific statement that predicts with excellent accuracy what will happen in particular situations (e.g. Acceleration = Force/Mass).

• A theory is a scientific principle that explains and predicts.

• Theories lead to testable hypotheses. Only theories that have withstood vigorous testing are accepted.

• “Scientific creationism” is not a scientific theory.

Darwin

ideas:

1. The idea that all living things share a common ancestor

2. The theory of evolution by natural selection: Living things appear very different today because of heredity and competition.

variation

• There are always differences between individuals in a population.

• Much of __ (but not all) is heritable.  Natural selection only works on heritable variation.

• Some __ affects the ability to survive and reproduce in a particular environment.  Natural selection only works on variation that affects fitness.

• Darwin was contemporary with Mendel. He did not understand heredity. At that time, most people still believed in blending inheritance; natural selection could not work if blending inheritance were right.

competition

Resources are limiting! Organisms compete for resources.

selection

makes some individuals more likely to contribute their genes to the next generation than others

artificial selection

used by breeders of plants and animals and by scientists: can select for size, growth rate, color, behavior, etc.

natural selection

occurs in nature because of limited resources—not every individual can breed, and genetic traits are one factor in determining breeding success

1. Organisms in populations will reproduce so long as there are resources to sustain them. Resources will be limiting. There is therefore competition for survival.

2. Organisms in populations are different. Some of these differences affect the chances of survival. Some differences are heritable (these are due to mutations).

3. The organisms with favorable traits will be more fit. They will pass these traits on to their offspring. Therefore, over time, populations will contain more and more of the fittest organisms.

divergence

Because the genes are redundant, the organism is fine if one of the genes changes over time

duplication

allows genomes to become more complex as they become larger, can result in redundant homologs

mutations

occur everywhere in our genome at random, but essential sequences tend to evolve more slowly because evolution weeds out so many mutants; less important parts of genes evolve more quickly