Genes, Environment, and Chance
character of all living organisms result from the interaction of environment and genes. For example, the risk of colon
cancer is increased by dietary factors such as high fat and low
fiber. But a certain genetic allele
(version of a gene sequence) in certain individuals confers a high risk
of colon cancer, even with a low-risk diet.
Kaiser, Science Magazine,
278:569 - 570, 24 Oct 1997
the information of a cell that is inherited by future cells. Each
cell needs to copy its chromosome exactly and pass on an identical copy
to each daughter cell. Of course rare "mistakes" occur -- cells actually have evolved to favor rare mistakes.Why?
(See Week 8, Molecular Evolution)
|A SAMPLING OF ENVIRONMENTAL GENES
lip & palate
|Locus on chrom. 17 in mice
|HLA-DP bet1 marker
beryllium disease (lung disorder)
designed to demonstrate the genetic or environmental component of a
trait generally aim to keep all components constant except the one
tested. As a result, someone who studies Down's Syndrome might
conclude that the basis of intelligence is genetics; whereas someone
studying lead poisoning would conclude that the basis of intelligence
is environmental. Actually, all traits -- appearance, development,
behavior -- depend on BOTH genes and environment.
Chance also determines the development of
an organism. For example individuals with the chromosome abnormality of
Down's Syndrome may develop by chance to a wide range of levels -- some
develop so badly they die before birth; others have severe heart
defects and other physical problems; mental delays vary from severe to
minor; some show few physical problems, and can attend college. None of
this variation can be predicted from the genes, only from chance
effects in development.
Levels of organization
in living systems
The content of
the Biology core courses can be viewed as a continuum:
History of Genetics
of years, humans have acted as agents of genetic selection, by breeding
offspring with desired traits. All our domesticated animals (dogs,
horses, cattle) and food crops (wheat, corn) are the result.
most of this time, humans had no idea how traits were inherited.
resemble parents (or don't) in bewilderingly complex ways. That
is because individuals in nature contain many genes,
and many different versions (alleles) of each gene. Consider these three individual
In 1866, Gregor Mendel
discovered independent assortment of traits, dominant and recessive
expression. Traits appear in pairs; separate independently in the
gametes; recombine in pairs, in offspring. (Today we know Mendel only
studied unlinked traits: on separate chromosomes, or so far apart that
crossover frequency approached 50%).
- What happens when you breed them? Try it out -- Orchid
cross. (To cross, click on one of the orchids.)
Mendel's work was lost. Only in the past century did humans learn
the fundamental mechanisms of heredity:
How and why
organisms resemble their parents; and how the inherited information
functions to make organisms look and behave as they do.
|1902 -- Walter Sutton and Theodore Boveri,
using dyes synthesized by the German organic chemistry industry,
observed that "colored bodies" in cells behaved in ways parallel to the
hypothetical agents of heredity proposed by Mendel. These bodies were
1905 -- Nettie Stevens observed in Tenebrio
beetles that all pairs of homologous chromosomes are the same size,
except for one pair which determines sex -- X, Y.
1909 -- Thomas H. Morgan correlates the X
chromosome with sex-linked inheritance of the white eye trait in Drosophila
-- a strain of flies discovered by an undergraduate lab
assistant, cleaning out old bottles of flies in Morgan's lab. Morgan
went on to make many important discoveries in fly genetics and linkage
analysis that apply to all diploid organisms.
1941 -- Beadle and Tatum determined in
Neurospora that each gene encodes one product (protein). (Later, we
learned that RNA can be a product, not always transcribed to protein;
for example, a ribosomal RNA.)
1944 -- Oswald Avery identified DNA as the
genetic material. Pieces of DNA can transfer genes into bacteria cells,
and transform them genetically.
||1953 -- Rosalind Franklin and Maurice Wilkins showed that DNA is a double helix.
Thomas Watson and Frances Crick determined the
structure of the base pairs which enable replication producing two
identical daughter helices.
1961 -- Jacob and Monod figured out regulation
of the lac operon.
1960's -- Barbara McClintockdiscovered
transposable elements in corn; later found in bacteria and animals.
1970 -- Temin and Balitimore discovered
reverse transcriptase in retroviruses; an enzyme later used to clone
genes based on the RNA encoding the product.
1977 -- Maxam, Gilbert, Sanger, others --
developed methods to sequence DNA.
|1981 -- The first transgenic mammals were made.
1987 -- Kary Mullis invented the polymerase
chain reaction (PCR), using a thermostable enzyme from a thermophilic
bacterium discovered by Thomas Brock at a geyser in Yellowstone. Mullis
sold the process to a pharmaceutical company, and earned very little.
Brock didn't earn a cent.
1995 -- The first bacterial genome sequence,
Haemophilus influenzae, was completely determined.
1996 -- Ian Wilmut cloned
the lamb Dolly from adult
mammary gland tissue.
1999 -- Completion of the first sequence of a
human chromosome, number 22.
2000 --Completion of the
2010 -- Whole organs
grown in culture?
2020 -- Chimp/human
hybrids demand human rights?
2050 -- Self-aware
computers demand human rights?
A genome is the total of all genetic sequence
in an organism. See The
Human Genome Project.
of Escherichia coli contains 4.6 million base pairs, encoding
genome contains 3 billion base pairs in the nucleus, but only
30,00-40,000 genes (estimated), taking up 3% of the sequence. The
rest includes regulator regions and large stretches of repetitive
sequence of unknown function.
genome has been sequenced for several microbes as well as several
animals and plants. Examples include:
Human (Homo sapiens)
Take a closer
look at three genomes:
Mouse (Mus musculus)
Fruit Fly (Drosophila melanogaster)
Nematode (Caenorhabditis elegans)
-- model plant
T. A. Brown, Genomes,
different organisms have a lot in common. Thus, we can use
model systems to make hypotheses about the biology of humans. We
can learn a surprising amount of human biology from genomes of yeast, C.
elegans, Drosophila, and the mouse. The latest model
genome proposed is the chimpanzee.
of microbes usually contain mainly genes
- Multicellular eukaryotes (animals and plants) have
their genes interspersed between large stretches of repetitive sequence (Satellite DNA).
- Genes of humans and other eukaryotes are interrupted
by introns of unknown function.
- As genomes evolve, some genes accidentally make extra
copies, which degenerate through mutations, becoming pseudogenes.
chimpanzee's genome could give us cancer-resistant genes.
create "model systems" for human diseases, we could put human disease
genes into chimps.
might the chimps have to say about it?
Prokaryotic cells (bacteria) contain their
chromosome as circular DNA. Usually the entire genome is a single circle,
but often there are extra circles called plasmids. The DNA is accessible to enzymes
that make RNA and protein (see Week 4, 5).
bacterial DNA is packaged in loops back and forth. The bundled
DNA is called the nucleoid. It concentrates the DNA in part of the cell,
but it is not separated by a nuclear membrane (as in
eukaryotes.) The DNA does form loops back and forth to a protein core, attached to the cell wall.
contain their DNA within the nuclear
|The DNA double helix is bound to proteins called histones. The
histones have positively charged (basic) amino acids to bind the
negatively charged (acidic) DNA. Here is an SDS gel of histone
proteins, separated by size (those migrating down farthest are smaller).
The DNA is wrapped around the histone core of eight
protein subunits, forming the nucleosome. The nucleosome is clamped by histone
H1. About 200 base pairs (bp) of DNA coil around one
histone. The coil "untwists" so as to generate one negative superturn
Science of Biology, by Purves, Orians, & Heller, 5th ed., 1997
image to see molecular structure
from Protein Data Bank (pdb 1aoi)
This form of DNA is active
chromatin; it can be "expressed"
(transcribed and translated) to make RNA and proteins (Week 4, 5).
After DNA has been replicated for mitosis (cell
division), the chromatin condenses.The nucleosomes zig-zag back and forth to form a flat
Science of Biology, by Purves, Orians, & Heller, 5th ed., 1997
forms a coil, which then loops back and forth attached to a nuclear matrix --
similar to the protein core of bacteria, but greatly extended.
During mitosis, several more layers of coiling result in fully condensed chromatin
(see textbook Ch. 9).
mitosis, the chromosomes appear as the thick rod-shaped bodies which
can be stained and visualized under light microscopy.
modern way to visualize condensed chromosomes is by FISH -- fluorescence in situ hybridization. In this method, fluorescent antibody-tagged
DNA probes hybridize to their complementary sequences in the
chromosomes. By using FISH probes with different colored
fluorophores, one can color each human chromosome independently, and
thus identify all 23 chromosomes. This is called chromosome painting.
reproduction, all cells need to copy their chromosomes exactly and pass
on an identical copy to each daughter cell. (Of course rare "mistakes"
occur -- cells actually have evolved to favor
rare mistakes. Why?)
different mechanisms do this in cells:
cell fission, in which the circular chromosome is replicated.
cell cycle, including Mitosis, in which multiple linear chromosomes
are separated and passed on.
Pathogenic E. coli attached
to human cell.
of the chromosome starts at the origin attached to the cell wall, near one pole of the cell.
Replication occurs bidirectionally around the chromosome, as the cell
replicating forks can start before the first cell division takes place.
This phenomenon allows an extremely rapid rate of reproduction.
DNA replication actually occurs in S phase of interphase. Interphase: G1,
growth; S, semiconservative synthesis of DNA; G2,
preparation for mitosis. Mitosis only
separates the newly replicated chromosomes; DNA replication
does not occur during mitosis.
problem with eukaryotes is that they have to replicate linear
chromosomes with special ends called telomeres. To
do this, they need to use a special enzyme called telomerase,
actually related to the reverse transcriptase of HIV virus.
Telomerase activity may play a crucial role in human aging; if the
chromosome ends fail to replicate properly, the chromosomes gradually
lose parts of their end sequence.
information on telomerase, go here.
gene can extend life of human cells, perhaps preventing aging!
(Or will it cause virulent cancer?)
Cell Division--Mitosis Click on picture for
Mitosis -- The Movie
produce sex cells
T. A. Brown, Genomes,
to chromosome copy number (ploidy) during DNA replication followed by
mitosis or meiosis?
-> 4N -> 2N
-> 4N -> 2N -> 1N
(1) Bacteria can divide TWICE in the time it takes to
complete replication of
their entire circle of DNA. (This is one reason kids
get sick so fast after
eating E.coli-contaminated hamburger.)
How is this possible? Can animal cells do the same
thing? Why or why not?
(2) Suppose that in a field of cells in tissue culture,
about five percent of cells show the condensed chromosomes of mitosis.
If the duration of mitosis is five minutes, what is the overall
generation time of the cells?
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