KAP
Biology Dept
Kenyon College
Genomes and Chromosomes
Fall Section Spring Section 1 Spring Section 2
Genomes
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 30,000 to 40,000 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 as well as a number of animals and plants. For example:

Human (Homo sapiens)
Mouse (Mus musculus)
Fruit Fly (Drosophila melanogaster)
Nematode (Caenorhabditis elegans)
Arabidopsis -- model plant

Take a closer look at three genomes:


T. A. Brown, Genomes, BIOS
  • Genomes of microbes usually contain mainly genes encoding proteins.
  • 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.
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.
  • The chimpanzee's genome could give us cancer-resistant genes.
  • To create "model systems" for human diseases, we could put human disease genes into chimps.

  • What might the chimps have to say about it?


Chromosome Structure

Prokaryotes
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

Eukaryotes
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.
 

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