Transcript Regulation and mutation

Gene regulation
Gene regulation
NUCLEUS
CYTOPLASM
R. S. Winning, 2003
Gene regulation
Transcription: regulated by activators (transcription factors)
and repressors (rare in eukaryotes)
Examples:
heat shock transcription factor
always present; becomes active when temperature changes
steroid hormones bind directly to TF to activate it
peptide hormones bind to cell membrane and initiate series of
reactions within the cell to activate TF
Gene regulation
transcription: regulated by activators (transcription factors)
and repressors (rare in eukaryotes)
RNA processing: different exons may be used within one gene,
producing different protein products
Gene regulation
transcription: regulated by activators (transcription factors)
and repressors (rare in eukaryotes)
RNA processing: different exons may be used within one gene,
producing different protein products
mRNA longevity: mRNA translates as long as it is intact
‘lifespan’ encoded in the 3' UTR
sequence AUUUA signals early degradation
Gene regulation
transcription: regulated by activators (transcription factors)
and repressors (rare in eukaryotes)
RNA processing: different exons may be used within one gene,
producing different protein products
mRNA longevity: mRNA translates as long as it is intact
‘lifespan’ encoded in the 3' UTR
sequence AUUUA signals early degradation
translation:
mRNA may exist without being translated
(not well understood)
Mutation
potential phenotypic effects of mutation:
morphological trait
– change in color, size
nutritional or biochemical variation
– loss of ability to synthesize a protein
- synthesis of different versions of a protein
change in behavior
– e.g., fruitflies - lose ability to recognize mate gender
changes in gene regulation
- gene turned off, or on
lethality
– loss of essential function
Mutation
Spontaneous mutations – errors in translation,
~ every 106 bases
repaired during translation by DNA polymerase ‘checking’
Induced mutations – due to mutagens
Point mutations
Single base substitutions
transitions - purine to purine, or pyrimidine to pyrimidine
transversions - purine with a pyrimidine or vice versa.
Point mutations
Single base substitutions
transitions - purine to purine, or pyrimidine to pyrimidine
transversions - purine with a pyrimidine or vice versa.
The fat cat ate the hot dog.
The fat car ate the hot dog.
The fat cat ate the hot hog.
small change in meaning,
still readable
no change (synonymous or silent mutations)
single amino acid change (missense mutation)
Point mutations
frameshift mutations
insertions
deletions
Point mutations
frameshift mutations
insertions
deletions
The fat cat ate the hot dog.
The fma tca tat eth eho tdo g.
profound change
Thf atc ata tet heh otd og
includes change in stop codon:
The fat cat ate the hot dog how why fry hot cat the…
Mutation
changes in larger segments of genome
- tandem duplications
addition of duplicate CAG sequences results in
Huntington’s chorea
- ploidy, aneuploidy
ploidy = number of chromosome sets in cell
haploid – 1 (gametes)
diploid − 2 (most cells)
triploid – 3 (sterile)
tetraploid – 4 ....etc.
Xenopus tropicalis
Xenopus laevis
Xenopus muelleri
Xenopus ruwensoriensis
2N = 20
2N = 36
2N = 72
2N = 108
diploid
tetraploid
octaploid
dodecaploid
ploidy = number of chromosome sets in cell
haploid – 1 (gametes)
diploid − 2 (most cells)
triploid – 3 (sterile)
tetraploid – 4 ....etc.
plants tend to have more ploidy levels – can overcome
sterility with vegetative reproduction
higher ploidy -> larger cells, more ‘product’
- yeast
- wheats
autopolyploidy vs. allopolyploidy
euploidy = correct number of chromosome sets in cell
polyploidy
aneuploidy = incomplete set of chromosomes
usually due to non-disjunction during meiosis
Down’s syndrome (trisomy 21)
Patau’s syndrome (trisomy 13)
Turner’s syndrome (monosomy of X chromosome)
Klinefelter syndrome (trisomy of sex chromosomes, XXY)
euploidy = correct number of chromosome sets in cell
polyploidy
aneuploidy = incomplete set of chromosomes
usually due to non-disjunction during meiosis
Down’s syndrome (trisomy 21)
Patau’s syndrome (trisomy 13)
Turner’s syndrome (monosomy of X chromosome)
Klinefelter syndrome (trisomy of sex chromosomes, XXY)
which is likely to have more severe effects, monosomy or trisomy?
Inversions – part of chromosome is flipped by 180
Translocations – non-homologous chromosomes exchange
material (not always symmetrically)
euploidy = correct number of chromosome sets in cell
polyploidy
aneuploidy = incomplete set of chromosomes
usually due to non-disjunction during meiosis
Down’s syndrome (trisomy 21)
Patau’s syndrome (trisomy 13)
Turner’s syndrome (monosomy of X chromosome)
Klinefelter syndrome (trisomy of sex chromosomes, XXY)
loss/variation/rearrangement of portions of chromosome
Cri-du-chat syndrome (loss of part of arm of chromosome 5)
Mutation
Somatic cell mutations – affect only individual
Gametic (germline) cell mutations – heritable
(e.g., cancer is largely unimportant evolutionarily)