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Genome and Environment Back to Top Syllabus

Genes, Environment, and Chance

The 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.

Polymorphism Class Environmental exposure Associated disease
CYP1A1 Activation Smoking Lung cancer
NAT2 Detoxification Smoking Bladder, breast cancer
GSTT1 (null) Detoxification Chlorinated solvents Cancer, toxicity
Paraoxonase Detoxification Nerve agents, pesticides Nervous system damage
HLA-H Nutritional factors Iron in diet Hemochromatosis
TGF-alpha Growth factor Maternal smoking Cleft lip & palate
Locus on chrom. 17 in mice Immune/inflammatory response Ozone Lung inflammation
HLA-DP bet1 marker Immune response Beryllium Chronic beryllium disease (lung disorder)
ALAD Biosynthesis Lead Lead poisoning
Jocelyn Kaiser, Science Magazine,  278:569 - 570,  24 Oct 1997
Genes contain 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)

Experiments 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

For thousands 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.

Yet for most of this time, humans had no idea how traits were inherited.  Why?
Offspring 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 orchids:

Orchid Photos
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%).

But 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 called chromosomes.

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 -- Thomas Watson and Frances Crick determined the double-helical structure of DNA, and 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.

2002 --Completion of the human genome?

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.

The genome of Escherichia coli contains 4.6 million base pairs, encoding 4,400 genes.

The human genome contains 3 billion base pairs in the nucleus, but only 60,000 genes (estimated), taking up 3% of the sequence.  The rest includes regulator regions and large stretches of repetitive sequence of unknown function.

The entire genome has been sequenced for several microbes, and for one simple animal, Caenorhabditis elegans.
Take a closer look at three genomes:

T. A. Brown, Genomes, BIOS

Genomes from 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.

Chromosome Structure Back to Top Syllabus

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).

From Bacterial Diversity

The 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.

From Bacterial Diversity

Eukaryotic cells contain their DNA within the nuclear membrane.
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).
From Virtual Fly Lab

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 per nucleosome.

Life, the Science of Biology, by Purves, Orians, & Heller, 5th ed., 1997
Click on 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 ribbon:

Life, the Science of Biology, by Purves, Orians, & Heller, 5th ed., 1997

The ribbon 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).

In mitosis, the chromosomes appear as the thick rod-shaped bodies which can be stained and visualized under light microscopy.
The 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.

Cell division

For 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?)

Two different mechanisms do this in cells:

Bacterial cell fission, in which the circular chromosome is replicated.

Eukaryotic cell cycle, including Mitosis, in which multiple linear chromosomes are separated and passed on.

Bacterial cell fission

Replication of the chromosome starts at the origin attached to the cell wall, near the midpoint of the cell. Replication occurs bidirectionally around the chromosome, as the cell elongates. New replicating forks can start before the first cell division takes place; this phenomenon allows an extremely rapid rate of reproduction.

Eukaryotic cell growth
In eukaryotes, 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.

The big 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.

For more information on telomerase, go here.
Telomerase gene can extend life of human cells, perhaps preventing aging!  (Or will it cause virulent cancer?)

Eukaryotic Cell Division--Mitosis Click on picture for stages:

Trent University, Biology Department

Mitosis -- The Movie

Division to produce sex cells

T. A. Brown, Genomes, BIOS

What happens to chromosome copy number (ploidy) during DNA replication followed by mitosis or meiosis?
Mitosis: 2N -> 4N -> 2N
Meiosis: 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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