BIM M 110 Section 7

May 20, 2009

George Chen
gtchen@ucsd.edu
www.scribd.com/g_chen 19
DAYS UNTIL
FINAL
 Announcements
● Final question format
● Regrades due tomorrow in class
● Pages 2 + 3 are added together
Human Evolution
● Laetoli
Footprints
● Lucy
Development of bipedalism
● Spinal cord
● Pelvis shape
● Knees
● Arm:leg ratio
● Predates tool
development, brain
growth
● Seen in other
species, but usually
limited
Homo floresiensis
Homo floresiensis
● 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
● Developmental
embryology
● Regulatory genes
 Dros Hox gene expression

McGinnis Lab, UCSD

 Hox mutations

● Recessive Ubx mutation leads to extra thoracic

segment + wings
 Developmental genes
● FOXP2
● Highly conserved
● Most significant mutations during human evolution
● Most recent mutation fixed in current population
● ASPN
● Many changes between chimpanzees and humans
● Microcephaly
● Chromosome 17?
● Bipedality
 Cancer
● Cancer – Latin for “crab” - tumor appeared to
look like a solid body with arms
● -carcinoma = epithelial tissue
● -sarcoma = non epithelial tissue
● -oma = benign tumor
● Leukemia & Lymphoma = blood cancer
 Cancer, defined
● A malignant and invasive growth of a tumor
● Benign
● Epidermal-Mesenchymal Transition (EMT)
● Metastasis

● Mutations are the proximate cause of cancer

● 20% in germline cells
● 90% in somatic cells
 Cancers are monoclonal
● Cancers require multiple mutations – easier to
occur in a single cell than multiple cells
● Mutations in cancer-critical genes:
● Oncogenes
● Tumor suppressor genes
 Oncogene
● Proto-oncogene – typically controls gene
expression, growth factors, signal transduction,
and apoptosis
● Requires a gain of function or loss of function
mutation
 Oncogene discovery
● Translocation mutations
● BCR-Abl
● IgH-Myc
● Bcl-2
● Retrovirus-induced cancers
● Rous sarcoma
● DNA recombinant technology in cell lines
● Loss of contact inhibition
 Tumor suppressor genes
● Retinoblastoma
● Uncontrolled cell proliferation
● BRCA1/BRCA2
● Repair DNA damage
● P53
● Apoptosis control
 Knudsen's 2-hit hypothesis
● A tumor suppressor gene may become
nonfunctional only when both alleles are
inactivated.
● Studied in Rb
● Loss of Heterozygosity (LOH)
 Metastasis
● 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