Bimm 110 Section 6 Slides

BIM M 110 Section 7 May 20, 2009 George Chen [email protected] www.pdfcoke.com/g_chen

19

DAYS UNTIL

FINAL

Announcements ●

Final question format

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Regrades due tomorrow in class

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Pages 2 + 3 are added together

Human Evolution ●

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Laetoli Footprints Lucy

Development of bipedalism ●

Spinal cord

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Pelvis shape

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Knees

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Arm:leg ratio

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Predates tool development, brain growth Seen in other species, but usually limited

Homo floresiensis

Homo floresiensis ● ●

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Brain close to Lucy's size Evidence of advanced toolbuilding, culture Does this disprove microencephaly as an ancient gene required for cognitive development?

Homeobox genes ●

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Developmental embryology Regulatory genes

Dros Hox gene expression

McGinnis Lab, UCSD

Hox mutations

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Recessive Ubx mutation leads to extra thoracic segment + wings

Developmental genes ●

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FOXP2 ●

Highly conserved

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Most significant mutations during human evolution

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Most recent mutation fixed in current population

ASPN ●

Many changes between chimpanzees and humans

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Microcephaly

Chromosome 17? ●

Bipedality

Cancer ●

Cancer – Latin for “crab” - tumor appeared to look like a solid body with arms

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-carcinoma = epithelial tissue

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-sarcoma = non epithelial tissue

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-oma = benign tumor

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Leukemia & Lymphoma = blood cancer

Cancer, defined ●

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A malignant and invasive growth of a tumor ●

Benign

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Epidermal-Mesenchymal Transition (EMT)

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Metastasis

Mutations are the proximate cause of cancer ●

20% in germline cells

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90% in somatic cells

Cancers are monoclonal ●

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Cancers require multiple mutations – easier to occur in a single cell than multiple cells Mutations in cancer-critical genes: ●

Oncogenes

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Tumor suppressor genes

Oncogene ●

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Proto-oncogene – typically controls gene expression, growth factors, signal transduction, and apoptosis Requires a gain of function or loss of function mutation

Oncogene discovery ●

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Translocation mutations ●

BCR-Abl

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IgH-Myc

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Bcl-2

Retrovirus-induced cancers ●

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Rous sarcoma

DNA recombinant technology in cell lines ●

Loss of contact inhibition

Tumor suppressor genes ●

Retinoblastoma ●

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BRCA1/BRCA2 ●

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Uncontrolled cell proliferation Repair DNA damage

P53 ●

Apoptosis control

Knudsen's 2-hit hypothesis ●

A tumor suppressor gene may become nonfunctional only when both alleles are inactivated.

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Studied in Rb

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Loss of Heterozygosity (LOH)

Metastasis ●

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Genes that specify for adhesion proteins and proteases for degradation usually targets for mutations Metastatic cancer cells often have high levels of matrix metalloproteinases (MMPs) Tissue inhibitors of metalloproteases (TIMPs) prevent metastasis and tumor invasion