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Today: Development and Genome Organization
Exam #2 W 7/9 in class
Development: differentiating cells to become
an organism
Cells function
differently because
they express
different
genes.
The proper control
of gene expression
is critical for proper
development.
So development in
animals is one way.
Inverse relationship between smoking and
weight: more smoking : less weight
Effect of smoking on
fetal development
and how that can
affect adults
Adults exposed to smoke as fetuses have
higher risk of obesity and heart disease
What is the connection?
Obesity, Diabetes, Heart Disease, High Blood
Pressure, Some Cancers all may have some
origins during fetal development.
Adults metabolism may react to poor nutrition
as fetuses…
Adaptation of Thriftiness
or
Catch Up Growth.
Adults metabolism may react to poor nutrition
as fetuses…Adaptation of Thriftiness or Catch
Up Growth.
Study of babies born during Dutch famine of
1944-45…
Adults metabolism may react to poor nutrition
as fetuses…Adaptation of Thriftiness or Catch
Up Growth.
Study of babies born during Dutch famine of
1944-45…
20 years later found that these babies had
higher rates of obesity.
Adults metabolism may react to poor nutrition
as fetuses…Adaptation of Thriftiness or Catch
Up Growth.
Study of babies born during Dutch famine of
1944-45…
20 years later found that these babies had
higher rates of obesity.
Precise mechanism is not known
What about smoking?
17,000 births studied and checked
at age 16 and 33.
Fetuses exposed to smoking had increased rate
of obesity.
What about smoking?
17,000 births studied and checked
at age 16 and 33.
Fetuses exposed to smoking had increased rate
of obesity and more smoking meant more
obesity.
What about smoking?
17,000 births studied and checked
at age 16 and 33.
Fetuses exposed to smoking had increased rate
of obesity and more smoking meant more
obesity.
For Mom’s who abstained during pregnancy, no
effect on fetus or as adult.
What about smoking?
17,000 births studied and checked
at age 16 and 33.
Fetuses exposed to smoking had increased rate
of obesity and more smoking meant more
obesity.
Smoking during first trimester had same effect
as during whole pregnancy.
What about smoking?
For diabetes more than 10 cigarettes per day
gave a 4 times greater risk of diabetes.
What about smoking?
Risk of high blood pressure also increases with
increased exposure to fetus of smoking during
pregnancy
Why?
Why?
Nicotine can inhibit hunger and increase energy
expenditure.
This can lead to poor fetal nutrition.
Why?
Nicotine causes constriction of blood vessels,
and may limit blood flow to the fetus.
Mammalian
circulation
AAL 38.8
Nicotine causes blood vessels to constrict
Why?
CO in blood decreases delivery of O2 to fetus.
Why?
These are all indirect affects leading to
“adaptation to thriftiness”…
Nicotine can inhibit hunger and increase energy
expenditure.
Nicotine causes constriction of blood vessels,
and may limit blood flow to the fetus.
CO in blood decreases delivery of O2 to fetus.
Why?
Nicotine and other toxins in smoke may
directly affect hormones that direct fetal
development.
Hormones are
molecules produced in
one cell and signal
another.
Why?
Nicotine and other toxins in smoke may
directly affect hormones that direct fetal
development.
Including hormones that direct brain
development.
So,
Smoking during pregnancy may have indirect
and/or direct affects on fetal development, and
these affects may manifest themselves in adults.
Correlation of weight and relatedness
Correlation of weight (BMI)
Identical twins reared together
Identical twins reared apart
Fraternal twins reared together
Biological siblings
Parents and children living together
Adopted children and parents
Unrelated children living together
%
80
72
43
34
26
4
1
The nature of environmental influences on weight and obesity: A behavior genetic analysis. Grilo, Carlos M.;
Pogue-Geile, Michael F.; Psychological Bulletin, Vol 110(3), Nov 1991. pp. 520-537. And two books by
Matt Ridley: Nature via Nurture (2003) and Genome: the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture:
Are traits coded for by genes fixed while traits
coded for by the environment are under our
control?
So development in
animals is one way.
Why?
Fig 23.3
Developmental mutants of
Drosophila melanogaster
Vertebrate
Development:
from zygote to adult
Early embryo development
Fig 19.13
Totipotent: ability to differentiate into any
cell-type
Totipotency is limited to early stages of animal
development
Why do cells lose totipotency?
Why do cells lose totipotency?
Mature,
differentiated plant
cells are totipotent
Why do cells lose totipotency?
•Gene expression can be
controlled at many points
between DNA and making
the final proteins.
•Changes in the various
steps of gene expression
control when and how
much of a product are
produced.
Why change gene expression?
•Different cells need different
components
•Responding to the
environment
•Replacement of
damaged/worn-out parts
Fig 10.21
DNA packaging
fluctuates…
genes being expressed
are unpackaged, genes
not needed are tightly
packaged.
Normally DNA is loosely
packaged
During mitosis DNA is tightly
packaged as chromosomes and
individually visible
Fig 3.8
Fig 10.21
DNA packaging
fluctuates…
Some of the tight
packaging of DNA is
irreversible.
Irreversible
packaging
of DNA
partially
explains the
loss of
totipotency.
Stem cells still have totipotency
Fig 19.13
Embryonic Stem Cells
are totipotent
Adult Stem Cells are
pluripotent (only form
some cell types)
Fig 19.14
What genetic mechanisms regulate/allow
development?
Fig 23.1
Increases in cell
number play a
role…
Fig 23.1
…so does cell
death.
Development of a mouse paw: yellow areas
show dying cells
CB 21.19
All humans
are female for
the first nine
weeks of
development
Fig 23.27
All humans
are female for
the first nine
weeks of
development
Fig 23.23
Flower parts:
Complexity from a
few simple genes
4 whorls of a flower
Each whorl expresses a specific
combination of three genes
Fig 23.24
Fig 23.23
Changing expression
of A, B, or C genes
changes organ identity
Fig 23.24
Fig 23.23
Flower parts:
Complexity from a
few simple genes
4 whorls of a flower
How does a cell know
where it is?
Fig 23.2
Drosophila
Development
Fig 23.4
Fig 23.5
Polarity development by mRNA localization
Hox genes regulate the identity of
body parts
Fig 23.11
embryo
Fig 23.11
adult
Expression of hox genes
in the embryo give rise
to different adult body
parts.
The order of Hox genes parallels the order of body
parts in which they are expressed
Fig 23.17
Drosophila and vertebrate Hox protein show striking
similarities (500 million years since common ancestor)
Fig 23.16
Many hox proteins have common sequences
(these are from Drosophila)
Fig 23.13
helix-turn-helix: a common DNA-binding motif
Fig 23.13
Many developmental genes are transcription factors
these are from Drosophila
Interaction of
genes can set
gradients in
cells/organisms
that signal how
different regions
should develop.
“Introduction to Genetic Analysis” 9th ed. ©2008 by Griffiths et al Fig 12.18
Reporter gene:
promoter
coding region
protein
promoter
reporter gene (luciferase, etc)
easily visualized protein
“Introduction to Genetic Analysis” 9th ed. ©2008 by Griffiths et al Fig 12.19
Interaction of
genes can set
gradients in
cells/organisms
that signal how
different regions
should develop.
“Introduction to Genetic Analysis” 9th ed. ©2008 by Griffiths et al Fig 12.18
Why change gene expression?
•Different cells need different
components
•Responding to the
environment
•Replacement of
damaged/worn-out parts
The order of Hox genes parallels the order of body
parts in which they are expressed
Fig 23.17
How are genomes organized?
25,000
Tbl 20.2
12
How does the organization of a genome
affect its function?
Map of human chromosome 20
http://www.ncbi.nlm.nih.gov/mapview/maps.cgi?ORG=human&CHR=X&MAPS=i
deogr[Xpter:Xqter],genes[1.00:153692391.00]
Comparison of Fugu and human huntingtin gene:
(green indicates transposons prevalent in human version)
7.5 X
bigger
both have 67
exons, connected
by lines
(puffer fish)
Figure 7-113 Molecular Biology of the Cell, 4th ed by Alberts et al
(Adapted from S. Baxendale et al., Nat. Genet. 10:67–76, 1995.)
Some genes have several similar sequences within the
genome: known as a gene family
Fig 8.7
Hemoglobin (carries O2 in the blood) is comprised of a
gene family in humans
Fig 8.7
Different members of the hemoglobin gene family are
expressed at different developmental stages
Fetal Hb
binds O2
more
strongly than
maternal Hb
Pseudogenes have the structure of a gene,
but are not expressed.
Most cells in an
organism have the
same DNA.
Which cells have
different DNA?
Fig 17.9
DNA is rearranged
in B-cells during
antibody production
Each B-cell
produces a
unique antibody
Fig 17.9
DNA
rearrangements in
B-cells allow each
B-cell to produce a
unique antibody
Recently Mobilized Transposons in the
Human and Chimpanzee Genomes (2006)
Ryan E. Mills et al. The American Journal of
Human Genetics 78: 671-679
and
Which transposable elements are active in
the human genome? (2007) Ryan E. Mills et
al. Trends in Genetics 23: 183-191
Transposons: mobile DNA
Transposons
comprise much of
human DNA
Fig 17.12C
Retro-transposons move via an RNA
intermediate
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Tbl 1
Recently
Mobilized Transposons
in the Human and
Chimpanzee Genomes
(2006) Ryan E. Mills et
al. The American
Journal of Human
Genetics 78: 671-679
Humans and
chimpanzees
shared a
common
ancestor
about 6
million years
ago
human
Humans have
more
transposons
than chimps
chimp
Fig 3
Recently
Mobilized Transposons
in the Human and
Chimpanzee Genomes
(2006) Ryan E. Mills et
al. The American
Journal of Human
Genetics 78: 671-679
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Conclusions:
•Transposons may play a role in evolution
•More abundant transposons in humans
show “recent” transposon activity
Conclusions:
•Transposons may play a role in evolution
•More abundant transposons in humans
show “recent” transposon activity
What affect do transposons have in humans?
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Fig 3
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E. Mills et al. The
American Journal of Human Genetics 78: 671-679
Does transposition cause disease?
Tbl 1
Which transposable elements are active in the human genome? (2007) Ryan E. Mills et al. Trends in
Genetics 23: 183-191
An active copy of the L1 transposon
‘jumped’ into the factor VIII gene and
caused hemophilia
Diseases caused by transposon insertion:
•Duchenne muscular dystrophy
•Coffin-Lowry syndrome
•Fukuyama-type congenital muscular dystrophy
(FCMD)
•colon cancer
•chronic granulomatous disease
•X-linked dilated cardiomyopathy
•familial hypocalciuric hypercalcemia and neonatal
severe hyperparathyroidism
•neurofibromatosis type 1
Which transposons are mobile?
Active human transposons have been
estimated to generate about one new
insertion per 10–100 live births
Which transposons are mobile?
Tbl 1
Which transposable elements are active in the human genome? (2007) Ryan E. Mills et al. Trends in
Genetics 23: 183-191
Comparative genomics also has been used to
identify recently mobilized transposons in
genetically diverse humans. For example, over 600
recent transposon insertions were identified by
examining DNA resequencing traces from 36
genetically diverse humans.
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Conclusions:
•Transposons may play a role in evolution
•More abundant transposons in humans
show “recent” transposon activity
•Transposons are still active, and can cause
mutations and disease.
Exam #2 W 7/9 in class