Biochemistry of Genetic Mechanisms

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Biochemistry of Genetic Mechanisms

"Periods of character stasis, strong variations in the rate of
character evolution and the appearance of new morphs controlled by
easily attributable and trivial genetic mechanisms are the mainstay of
species-level taxonomy in the fossil record" (Levinton). Almost all
living organisms use the same basic biochemical molecules (e.g., DNA,
RNA, the same 20 amino acids & ATP) and many identical or nearly
identical enzymes. There are 4 standard nucleotide bases (adenine,
thymine, guanine & cytosine) in DNA. Sugar and phosphate can be bonded
(glued) together; this makes the assembly of the nucleotides along a
long strand possible. This long strand has a backbone made of sugar
and phosphate, which repeats and repeats along a line. The nucleotide
bases attach to the sugar molecules in different sequences along this
line. The nucleotide bases of the DNA molecule form complementary
pairs; the nucleotide base (hydrogen) bonds to another nucleotide base
in a strand of DNA opposite to the original strand of DNA, forming a
complementary chain. This (hydrogen) bonding is specific; adenine
always bonds to thymine (& vice versa) and guanine always bonds to
cytosine (& vice versa). This bonding occurs across the molecule,
leading to a double-stranded system. DNA replicates itself for cell
division and reproduction. Different portions of the DNA on the
chromosome are active at different times during development and adult
life. New life starts small and follows its ontogeny pathway through
phylogeny, guided by developmental genes. The gene is a linear DNA
segment of a chromosome that codes for one protein. The genome is the
entire DNA contained in an organism or a cell, which includes both the
chromosomes within the nucleus and the DNA in mitochondria.

DNA is decoded in two steps. Transcription of DNA into a form of
complementary purine or pyrimidine nucleotides of RNA is followed by
translation into a sequence of amino acids. Organisms utilize DNA
triplet code; three nucleotide bases code for an amino acid. These
triplets are called codons; each one codes for a specific amino acid in
life's 20 amino acids used to construct proteins. Not only are the
same codons assigned to the same amino acids, they are also assigned to
the same "start" and "stop" signals in the vast majority of
genes in animals, plants, and microorganisms. Some exceptions have
been found.
The genetic code can be examined further; it is almost universal. The
genetic code can be expressed as either DNA codons or RNA codons. The
genetic code consists of 64 triplets of nucleotides. Each of the 64
codons specifies one of 20 amino acids or else serves as a punctuation
mark signaling the end of a message. Having this many triplets
produces some redundancy in the code, most of the amino acids being
encoded by more than one codon. The genetic code is also degenerate;
i.e., there is some flexibility as to which base occupies a particular
position, so there is another way to have more than one codon per amino
acid. Given 64 codons, punctuation marks and 20 amino acids, there
are 10 to the 83rd power possible genetic codes. As stated
previously, the gene, the DNA portion of the chromosome that makes a
protein, acts as a template for the synthesis of RNA in transcription.
Only a part of this DNA is transcribed to produce nuclear RNA (nRNA),
and only a minor portion of the nuclear RNA survives the RNA processing
steps. In most mammalian cells, only 1% of the DNA sequence is copied
into a functional RNA (mRNA).
One of the most important stages in RNA processing is RNA splicing. In
many genes, the DNA sequence coding for proteins, called "exons,"
may be interrupted by stretches of non-coding DNA, called
"introns." In the cell nucleus, the DNA that includes all the
exons and introns of the gene is first transcribed into a complementary
RNA copy of "nuclear RNA" or nRNA (previously discussed). In a
second step, introns are removed from nRNA by the process of RNA
splicing. The edited sequence is "messenger RNA," or mRNA. The mRNA
leaves the nucleus and travels to the cytoplasm, where it encounters
the ribosomes. The mRNA, which carries the gene's instructions,
dictates the production of proteins by the ribosomes. The amino acids
used to make the proteins are carried to the ribosome site by "transfer
RNAs."
Closer examination of RNA splicing, where introns (the internal
sequences interrupting protein-encoding parts on the long strands of
precursor RNA) are processed (by the removal of these apparently
functionless internal "spacer" sequences), reveals that this
functionless spacer material does have some function. Nucleic acids
have potential to form intra-strand stem-loop structures if the
complementary nucleotide bases are suitably located. For many taxa, if
transcription is to the right, the top (mRNA synonymous) DNA strand has
purine-rich loop potential; if transcription is to the left, the top
(template) strand has pyrimidine-rich loop potential. The general
function of stem-loops is moderating recombination. In other words,
the order of nucleic acid bases has potential to form stem-loop
structures; these facilitate error-correction in recombination. In
rapidly evolving genomes, nucleotide base-order dependent stem-loop
potential is as important as other functions. Nucleotide base order
serves either recognition for regulatory factors or the encoding of a
protein. There appears to be circumstances under which nucleotide base
order synergizes with, or antagonizes, nucleotide base composition in
determining total stem-loop potential. There is room for conflict
(base order serves many local "strategies", whose demands may conflict)
between the "desires" of a sequence to encode both a protein (+
non-messenger RNA) and stem-loop potential. The conflict would be
particularly apparent in the case of genes under very strong positive
phenotypic (Darwinian) selection, as in the case of genes affected by
"arms races" with predators or prey. The stem-loop potential of a DNA
sequence is unlikely to be just a passive and indirect consequence of
the action of various evolutionary pressures on DNA. There appear to
be powerful genome-wide pressures which actively confer or inhibit the
potential to form stem-loops. Many organisms share the same introns
and types of repeats. .
There are 3 types of RNA; all are involved in protein synthesis. In
addition to mRNA, and the previously-mentioned transfer RNA (tRNA) that
carries the amino acids to the ribosome, there is ribosomal RNA (rRNA).
Ribosomes are the sites where the cell assembles proteins according to
genetic instructions. A bacterial cell may have a few thousand
ribosomes; a human cell has a few million ribosomes. Cells that have
high rates of protein synthesis have particularly great numbers of
ribosomes. Cells active in protein synthesis also have prominent
nucleoli, which make the ribosomes. Ribosomes are particles composed
of about 60% rRNA and 40% protein (enzymes). Ribosomes are suspended
in the cytosol and are also bound to the endoplasmic reticulum. These
ribosomes are respectively called free ribosomes and bound ribosomes.
They translate the information encoded in messenger RNA (mRNA) into a
polypeptide. The sequence of amino acids in a polypeptide is dictated
by the codons in the messenger RNA (mRNA) molecules from which the
polypeptide was translated. A number of ribosomes may be attached to
the same messenger, each manufacturing its own chain of polypeptides.
Transfer RNA carries the amino acids, as high-energy esters, to the
ribosome. The genetic code is the same in all living organism; it has
been demonstrated that eukaryotic ribosomes are able to translate
bacterial mRNAs correctly.
In the ribosome, the tRNA base pairs with in a specific way with the
mRNA (the template RNA). A particular sequence of nucleotides can
specify a particular sequence of amino acids by means of transfer RNA
(tRNA) molecules, each specific for one amino acid and for a particular
triplet (codon) of nucleotides in mRNA. The family of tRNA molecules
enables the codons in a mRNA molecule to be translated into the
sequence of amino acids in the protein. At least one kind of tRNA is
present for each of the 20 amino acids used in protein synthesis. Some
amino acids use two or three different kinds of tRNA; most cells
contain as many as 32 different kinds of tRNA. The amino acid is
attached to the appropriate tRNA by an activating enzyme specific for
that amino acid as well as for the tRNA assigned to it. Each kind of
tRNA has a sequence of 3 unpaired nucleotides, the anticodon, which can
bind, following the rules of base pairing, to the complementary triplet
of nucleotides (codon) in a messenger RNA (mRNA) molecule. As DNA
replication and transcription involve base pairing of nucleotides
running in opposite direction, the reading of codons in mRNA also
requires that the anticodons bind in the opposite direction.
Proteins are formed by peptide linkages between the amino acids.
Proteins are the basic components of protoplasm in the cells of animals
and plants; they are the "building blocks" of the structural
components of the body; collagen is an important structural protein.
Proteins are involved in every cellular process. Many hormones and
nearly all enzymes are proteins. Enzymes enhance chemical reactions at
life-friendly temperatures. Proteins are also involved in transport
(hemoglobin), storage (casein), contraction (actin/myosin), protection
(antibodies) and defensive toxins. Protein molecules contain nitrogen
(+ some sulfur). Nitrogen-fixing bacteria (e.g. on bean/legume roots)
and blue-green algae convert inert atmospheric nitrogen and bind it
with hydrogen, creating ammonia (NH3). NH3 is a more
biochemically-available form of nitrogen. NH3 is oxidized by nitrite
(NO2-) forming and nitrate (NO3-) forming bacteria. Green plants
absorb nitrates and reduce them to ammonium ions (NH4+). Ammonium ions
are used to make amino acids in the chemistry of respiration.
Not all cellular DNA is in the nucleus; some is in the mitochondria.
Mitochondria also contain RNA as well as enzymes for protein synthesis.
Mitochondrial DNA and RNA are inherited maternally and bear a closer
resemblance to bacterial nucleic acid than to animal nucleic acid.
Mitochondria conduct cellular respiration. The major function of
mitochondria is to convert food energy to the chemical energy of the
cell, adenosine triphosphate (ATP). Human mitochondria have
information contained in approximately 16,500 nucleotides (paired), 2
ribosomal and 22 transfer RNAs. Mitochondrial DNA codes for the
synthesis of 13 proteins, all components of the oxidative
phosphorylation system. Mitochondrial DNA does not contain information
for all mitochondrial proteins; most are coded by nuclear genes. Most
mitochondrial proteins are synthesized in the cytosol, from
nuclear-derived mRNAs. They are then transported to the mitochondria,
where they contribute structural and functional elements to the
organelle.
Mutations are caused by both chemical and physical agents, although the
action of physical agents (e.g. ionizing radiation) can usually be
explained by a chemical mechanism. Regardless of the agent that causes
the mutation, none is selective in the sense that it will mutate 1 gene
and not another. All genes are composed of 4 different types of purine
or pyrimidine bases; an agent that may specifically react with only 1
of the 4 could potentially cause mutations in every gene. Mutations
may be produced in many ways. Nucleotide bases may be deleted or new
ones may be inserted. More frequently, existing bases are chemically
modified so that on replication, improper base pairing will cause a
different base to appear at the modified position. Mutations are
random events. During evolution, environmental selection eliminated
large numbers of harmful mutations. Most of the time, the insertion of
the wrong amino acid would cause an inability in the function of a
protein. If the amino acid replacement occurs at a less important
position, activity may not be affected at all (neutral variation).
There may even be a beneficial improvement in activity. On occasion, a
small number of helpful mutations gave life survival value. As life
becomes more complex, greater numbers of mutations (understandably)
become increasingly harmful.
Unlike mutation agents that alter the molecular structure of DNA, there
are agents that promote the expression of genetic information coded in
the DNA. Promoting agents include a variety of substances, such as
hormones, protein growth factors, and plant products. These substances
influence genetic expression by binding to receptors on cell surfaces,
or in the cytoplasm, or in the nucleus. The action of promoting agents
is reversible. In-between mutation agents and promoting agents are
initiating agents. Initiating agents alter DNA structure and may cause
somatic mutations over the lifetime of an individual. Irreversible
changes similar to a mutation can occur, but phenotypic change is not
necessarily obligatory. It programs the cells so that exposure to a
promoting agent causes a response, as in the formation of cancerous
cells.
The biochemistry of genetic mechanisms is a part of the biochemistry of
metabolism. Metabolism, the total sum of all chemical processes in
living organisms, includes not only the biochemistry of genetic
mechanisms, but it also includes other areas of protoplasm production
(growth/development) and maintenance (vital function), as well as
respiration (energy production), and detoxification (rendering waste
products harmless). Metabolism requires a power source. The
metabolism of the more familiar surface life is dependent on the
biochemistry of photosynthesis.


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