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Genetics summary chapter 10 VU amsterdam
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This summary covers complete chaper 10 of genetics at the Vrije Universiteit Amsterdam.
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Chapter 10Chromosomes are the structures within living cells that contain the genetic material. The term
genome refers to the entire complement of genetic material in an organism or species (the total
amount of genetic information in the chromosomes of an organism, including its genes and other
functional and non-functional sequences). For bacteria, the genome is typically a single circular
chromosome. For eukaryotes, genetic material is found in different cellular compartments. The
nuclear genome in humans includes 22 autosomes, and one pair of sex chromosomes which consist
of XX or XY. Eukaryotes also have a mitochondrial genome, and plants have a chloroplast genome.
The primary function of the genetic material is to store the information needed to produce the
characteristics of an organism. The sequence of bases in a DNA molecule stores information. To fulfil
their role at the molecular level, chromosomal sequences facilitate 4 important processes:
1. The synthesis of RNA and cellular proteins,
2. The replication of chromosomes,
3. The proper segregation of chromosomes
4. The compaction of chromosomes so that they fit in living cells.
The genome of eukaryotes is made up of a single, haploid set of chromosomes. Bacteria are haploid.
Mitochondrial or chloroplast genomes are single circular DNA containing its genes and other
sequences. Viral genome is made of DNA/RNA.
Bacterial chromosomes
In most species, the chromosomal DNA is a circular molecule, though some bacterial species have
linear chromosomes. Although bacteria usually contain a single type of chromosome, more than one
copy of that chromosome may be found within one bacterial cell. A typical bacterial chromosome is a
few million base pairs in length. A bacterial chromosome commonly has a few thousand different
genes, which are interspersed throughout the entire chromosome. Protein-encoding genes
(structural genes) account for the majority of bacterial DNA.
- Intergenic regions: stretch of DNA sequences located between genes. Intergenic regions are
a subset of noncoding DNA.
Other sequences in chromosomal DNA influence DNA replication, gene transcription, and
chromosome structure. For example, bacterial chromosomes have an origin of replication – a
sequence of DNA at which replication is initiated on a chromosome, plasmid or virus. Also, a variety
of repetitive sequences – are patterns of nucleic acids (DNA or RNA) that occur in multiple copies
throughout the genome – have been identified in many bacterial species. These sequences are found
in multiple copies and are usually interspersed within the intergenic regions throughout the bacterial
chromosome. Repetitive sequences may play a role in a variety of genetic processes, including:
- DNA folding,
- DNA replication,
- Gene regulation,
- Genetic recombination
Some repetitive sequences are transposable elements (jumping genes): a DNA sequence that can
change its position within a genome. They increase genetic diversity and play an important part in
evolution.
Inside a bacterial cell, a chromosome is highly compacted and found within a region of the cell called
the nucleoid. Depending on the growth conditions and phase of the cell cycle, bacteria may have 1-4
identical chromosomes per cell. In addition, the number of copies varies depending on the bacterial
species. Each chromosome is found within its own distinct nucleoid in the cell. Unlike the eukaryotic
, nucleus, the bacterial nucleoid is not a separate cellular compartment surrounded by a membrane.
Rather, the DNA in a nucleoid is in direct contact with the cytoplasm of the cell.
To fit within a bacterial cell, the chromosomal DNA must be compacted about 1000-fold. The loops
that eliminate from the core (chromosome picture) are called microdomains. They are typically
10,000 bp in length. The length and boundaries of these microdomains are thought to be dynamic,
changing in response to environmental conditions. In E. Coli, the microdomains are further organised
in macrodomains. To form microdomains and macrodomains, bacteria use a set of DNA-binding
proteins called nucleoid-associated proteins (NAPs) that facilitate (vermakkelijken) chromosome
compaction and organization. These proteins either bend the DNA or act as bridges that cause
different regions of DNA to bind to each other. NAPs also facilitate chromosome segregation and play
a role in gene regulation. Examples of NAPs are H-NS and SMC proteins. SMCs are also found in
eukaryotes. However, it is important to note that not every bacterial species have their
chromosomes organized in microdomains and macrodomains.
DNA supercoiling further compacts the bacterial chromosome
Because DNA is a long thin molecule, twisting forces can dramatically change its conformation. This
effect is similar to what happens when you twist a rubber band. If twisted in one direction, a rubber
band eventually coils itself into a compact structure as it absorbs the energy applied by the twisting
motion. Because the two strands of DNA already coil around each other, the formation of additional
coils due to twisting forces is referred to as DNA supercoiling. The DNA within microdomains is
further compacted because of DNA supercoiling.
Because B DNA is a right-handed helix, underwinding is a left-handed twisting motion, and
overwinding is a right-hand motion. The underwinding force can cause: fewer turns and the
formation of a negative supercoil. A right-handed twist (overwinding) can produce more turns and a
positive supercoil.
- The different DNA conformations due to supercoil are called topoisomers of each other.
Chromosome function is influenced by DNA supercoiling
The chromosomal DNA in living bacteria is negatively supercoiled. Negative supercoiling has
important consequences. As already mentioned, the supercoiling of chromosomal DNA makes it
much more compact. Therefore, supercoiling helps to greatly decrease the size of the bacterial
chromosome. In addition, negative supercoiling also affects DNA function. To understand how it does
so, remember that negative supercoiling is due to an underwinding force of the DNA. Therefore,
negative supercoiling creates tension on the DNA strands that may be released by their separation.
Although most of the chromosomal DNA is negatively supercoiled and compact, the force of the
negative supercoiling may promote DNA separation in small regions. This increases genetic activities
such as replication and transcription that require the DNA strands to be separated.
DNA gyrase (topoisomerase II)
In 1976, Martin Gellert and colleagues discovered the enzyme DNA gyrase, also known as
topoisomerase II. This enzyme, which contains 4 subunits (2 A and 2 B subunits) introduces negative
supercoiling (or relaxes positive supercoiling) using energy from ATP. To alter supercoiling, DNA
gyrase has two sets of jaws that allow it to grab into two regions of DNA.
1. DNA binds to the lower jaws
2. DNA wraps around the A subunits in a right-handed direction. (the A subunits are the lower
jaws)
3. Upper jaws clamp onto DNA
4. DNA held in lower jaws is cut. DNA held in upper jaws is released and passes downward
through the opening in the cut DNA. This process uses 2 ATP molecules.
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