Transcription regulation
o Transcription factors (protein) bind to enhancers or silencers
(DNA) to affect transcription. Enhancers increase transcription when bound, while silencers decrease it. The main difference in eukaryotes that sets them apart from prokaryotes is that
enhancers/silencers can be very far away from the actual
promoter, and can be upstream or downstream. The DNA must loop back on itself so that the transcription factor bound to enhancer/silencer can actually make contact with the promoter. Intermediate proteins are involved in the process.
o Eukaryotes lack the bacterial transcription regulation
mechanisms such as the operon (exists but very rare) and attenuation.
o DNA-binding proteins bind to DNA.
o transcription factors bind to DNA, so they have a DNA-binding
domain.
o DNA-binding domains interact with the grooves in the double
helix (major grooves and minor grooves).
o Advanced: common DNA-binding domains include helix-turn-
helix (HTH), zinc finger, basic-region leucine zipper (bZIP).
Cancer as a failure of normal cellular controls, oncogenes
o Failure of normal cellular controls:
Cancer cells continue to grow and divide in situations
normal cells would not.
Cancer cells fail to respond to cellular controls and signals
that would halt this growth in normal cells.
Cancer cells avoid apoptosis (self-destruction) that normal
cells undergo when extensive DNA damage is present.
Cancer cells stimulate angiogenesis (cause new blood
vessels to grow to nourish the cancer cell).
Cancer cells are immortal while normal cells die after a
number of divisions.
Cancer cells can metastasize - break off and then grow in
another location.
o Oncogenes: genes that cause cancer when activated. The
product of many oncogenes are involved in speeding up cell division. Before an oncogene is activated, it is a harmless proto- oncogene. Something occurs that changes the proto-oncogene to an oncogene. The classic exampe of oncogene is the src.
o Tumor suppressors: if the oncogene is the "bad" gene, tumor
suppressors are the "good" genes. The product of many tumor suppressors are involved in slowing down or controlling cell division. If something happens that cause the tumor suppressor to no longer function, then the cell becomes cancerous. The classic example of tumor suppressor is the p53.
Post-transcriptional control
o tRNAs and rRNAs modifications: some normal nucleotides are
modified to control the structure of these RNAs.
o mRNAs modifications
RNA splicing: sequences called introns are cut out,
sequences called exons are kept and and spliced (joined) together.
Alternate splicing: different ways of cutting up and RNA
and rejoining the exons pieces make different final RNA products.
5' capping and 3' poly-A tail: these help to protect the RNA
from degradation so they can last longer.
o After the correct modifications, RNA is transported out of the
nucleus where they can function in translation.
o After some time, RNA is degraded. The rate and timing of RNA
degradation can be controlled by the cell.
Mendelian concepts
Phenotype and genotype
o Phenotype: what is observed. For example, height, color,
whether the organism exhibits a trait.
o Genotype: the genetic make up. For example, homozygous
dominant (TT), heterozygous (Tt), homozygous recessive (tt).
Gene: a gene is a stretch of DNA that codes for a trait. In molecular
biology, the gene codes for a protein, which acts to bring about a trait.
Locus: location (of a gene) on a chromosome. Allele: single and multiple
o An allele is a variant of a gene. A gene may have a number of
alleles. All alleles of the same gene exist at the same locus.
o A cell holds 2 alleles of each gene. One allele from mom, one
o When a gene has only 2 alleles, then that's the simple case
we're used to seeing. For example, the trait for height in peas is governed by T and t. TT and Tt gives tall plants, and tt gives short ones.
o When a gene has more than 2 alleles, then that's called multiple
alleles. For example, blood type is governed 3 alleles: IA IB and i. Because a cell can only hold 2 of these alleles, the different
combinations an individual can have are: Genotype Blood type (phenotype)
IAIA or IAi A IBIB or IBi B IAIB AB
ii O
Homo- and heterozygosity
o Homozygous: when the two alleles that an individual carries are
the same. For example, AA or aa.
o Heterozygous: when the two alleles that an individual carries are
different:. For example, Aa.
Wild type: the "normal" allele or phenotype for an organism. The wild-
type is usually the most prevalent, although it doesn't necessarily have to be true.
Recessiveness: the "weak" allele. The recessive allele is only
expressed if both copies are present. Only a single copy is needed for the dominant allele. The recessive allele is usually denoted as the lower case letter, the dominant allele is usually denoted as the upper case letter. For example, blond hair is recessive. Both alleles for blond hair need to be present, otherwise the hair is dark.
Complete dominance Genotype Phenotype AA Dominant Aa Dominant aa Recessive Co-dominance
Genotype Phenotype
AA A
AB Both A and B
BB B
An example of co-dominance is the A and B blood type alleles. Type A cells have A antigens. Type B cells have B antigens. Type AB makes both antigens.
Incomplete dominance, leakage, penetrance, expressivity
o Incomplete dominance: Genotype Phenotype AA A AB In between A and B BB B o
An example of incomplete dominance is the color of chickens. A cross between black chickens and white chickens give rise to bluish grey chickens.
o leakage: gene flow from one species to another.
o Penetrance is the frequency that a genotype will result in the
phenotype. 100% penetrance means that if you have the genes for being smart, then you'll definitely be smart! Less than 100% penetrance means that you may have the genes for being smart, but you may not actually be smart.
o Expressivity is to what degree a penetrant gene is expressed.
Constant expressivity means that if your genes for being smart manages to penetrate (show up as a trait), then your IQ is 120. Variable expressivity means that your IQ doesn't have to be 120, it could be somewhat lower or somewhat higher.
Gene pool: all of the alleles in a population.