MOLECULAR PHYLOGENY
Molecular phylogenetics is the science of using DNA and protein
sequences from different species or populations to infer their evolutionary
relationships, which are represented as a phylogeny or tree. The field
originated in the 1960s when protein sequences became available and
have gone through explosive growth in recent years due to accumulation
of genomic sequence data. Major methods of phylogeny inference include
parsimony, which infers the tree by minimizing the required number of
character changes, distance-based cluster algorithms, as well as
statistical inference methods such as maximum likelihood and Bayesian.
Molecular phylogenetics had a huge impact on studies of human evolution
by showing in the 1990s that homo sapiens is closely related to the
African apes (chimpanzees and gorillas), and continue to provide
important tools for the interpretation of genomic data from the humans
and the apes.
BIOINFORMATICS
Bioinformatics is the application of computer technology to the
understanding and effective use of biological and biomedical data. It is the
discipline that stores, analyses and interprets the big data generated by
life-science experiments, or collected in a clinical context. This
multidisciplinary field is driven by experts from a variety of backgrounds:
biologists, computer scientists, mathematicians, statisticians and
physicists.
The classic data of bioinformatics include DNA sequences of genes or full
genomes; amino acid sequences of proteins; and three-dimensional
structures of proteins, nucleic acids and protein–nucleic acid complexes.
Additional “-omics” data streams include: transcriptomics, the pattern
of RNA synthesis from DNA; proteomics, the distribution of proteins
in cells; interactomics, the patterns of protein-protein and protein–nucleic
acid interactions; and metabolomics, the nature and traffic patterns of
transformations of small molecules by the biochemical pathways active in
cells. In each case there is interest in obtaining comprehensive, accurate
data for particular cell types and in identifying patterns of variation within
the data.
Bioinformatics has been driven by the great acceleration in data-
generation processes in biology. Genome sequencing methods show
perhaps the most dramatic effects. In 1999 the nucleic acid sequence
archives contained a total of 3.5 billion nucleotides, slightly more than the
length of a single human genome; a decade later they contained more
than 283 billion nucleotides, the length of about 95 human genomes. The
U.S. National Institutes of Health has challenged researchers by setting a
goal to reduce the cost of sequencing a human genome to $1,000; this
would make DNA sequencing a more affordable and practical tool for U.S.
hospitals and clinics, enabling it to become a standard component
of diagnosis.
Restriction fragment length polymorphism (RFLP)
Restriction fragment length polymorphism (abbreviated RFLP) refers to
differences (or variations) among people in their DNA sequences at sites
recognized by restriction enzymes. Such variation results in different sized
(or length) DNA fragments produced by digesting the DNA with a
restriction enzyme. RFLPs can be used as genetic markers, which are
often used to follow the inheritance of DNA through families.
RFLPs have been very useful to use as markers for following a genomic
DNA, either from human or other animals. What is it, though? So basically,
if you follow the sequence of DNA, particular sites, a series of four to eight
nucleic acids, results in a restriction site where an enzyme from bacteria
can actually bind and cleave that DNA. So why is that useful? Well, we can
take advantage of this fact to actually look for differences between people
if they have that restriction enzyme site or not. So a single base difference
between two people could result in either the presence or absence of that
restriction site. So then, if you isolate that piece of DNA surrounding that
site from two people, from one of them it will be cut by the enzyme and
the other one it won't. And that results in a polymorphism, or difference
between those two people. We typically see these, or we monitor these,
by isolating the DNA, cutting it with that bacterial restriction enzyme, and
running it on a gel using electrophoresis. In one person, without the
enzyme site you'll see one band, and the person that has the enzyme site,
you'll see two bands, representing the two cleaved products. So these
differences in nucleic acid sequences and restriction enzyme binding sites
just mean that there's a difference in the sequence between those two
people. That sequence difference doesn't necessarily mean that there's a
disease associated with it. It's a polymorphism that we could use to follow
the inheritance of DNA.
Single nucleotide polymorphisms (SNPs)
Single nucleotide polymorphisms, frequently called SNPs (pronounced
“snips”), are the most common type of genetic variation among people.
Each SNP represents a difference in a single DNA building block, called a
nucleotide. For example, a SNP may replace the nucleotide cytosine (C)
with the nucleotide thymine (T) in a certain stretch of DNA.
SNPs occur normally throughout a person’s DNA. They occur almost once
in every 1,000 nucleotides on average, which means there are roughly 4
to 5 million SNPs in a person's genome. These variations occur in many
individuals; to be classified as a SNP, a variant is found in at least 1
percent of the population. Scientists have found more than 600 million
SNPs in populations around the world. SNPs differ from substitution
variants, which replace one DNA building block (nucleotide) with another.
Substitution variants usually cause disease and are generally not found in
1 percent of any population. Additionally, SNPs differ from copy number
variants (CNVs), which occur when a whole gene (or other large section of
DNA) is duplicated or deleted. Most commonly, SNPs are found in the DNA
between genes. They can act as biological markers, helping scientists
locate genes that are associated with disease. When SNPs occur within a
gene or in a regulatory region near a gene, they may play a more direct
role in disease by affecting the gene’s function.
GENETIC CONSEQUENCES OF INBREEDING
Inbreeding is the process of mating genetically similar organisms. In
humans, it's associated with consanguinity and incest, in which close
relatives have sexual relationships and children. Inbreeding violates
modern social norms but is fairly common in animals and plants. While
inbreeding generally is considered negative, it also offers some positive
effects.
Inbreeding occurs when two closely related organisms mate with
each other and produce offspring.
The two main negative consequences of inbreeding are an
increased risk of undesirable genes and a reduction in genetic
diversity.
The House of Habsburg may be the best example of the effects of
inbreeding in humans.
Genetic Effects of Inbreeding
When two closely related organisms mate, their offspring have a higher
level of homozygosity: in other words, an increased chance that the
offspring will receive identical alleles from their mother and father. In
contrast, heterozygosity occurs when the offspring
receives different alleles. Dominant traits are expressed when only one
copy of an allele is present, while recessive traits require two copies of an
allele to be expressed.
Homozygosity increases with subsequent generations, so recessive traits
that might otherwise be masked may start appearing as a result of
repeated inbreeding. One negative consequence of inbreeding is that it
makes the expression of undesired recessive traits more likely. However,
the risk of manifesting a genetic disease, for example, isn't very high
unless inbreeding continues for multiple generations.
The other negative effect of inbreeding is the reduction genetic diversity.
Diversity helps organisms survive changes in the environment and adapt
over time. Inbred organisms may suffer from what is called reduced
biological fitness.
Scientists have also identified potential positive consequences of
inbreeding. Selective breeding of animals has led to new breeds of
domestic animals, genetically suited to specific tasks. It can be used to
preserve certain traits that might be lost from out-crossing. The positive
consequences of inbreeding are less well studied in humans, but in a
study of Icelandic couples, scientists found that marriages between third
cousins resulted in a greater number of children, on average than those
between completely unrelated couples.
Disorders from Inbreeding
The risk of a child developing an autosomal recessive disorder increases
with inbreeding. Carriers of a recessive disorder may be unaware they
possess a mutated gene because two copies of a recessive allele are
needed for gene expression. On the other hand, autosomal dominant
disorders are seen in the parents but might be eliminated through
inbreeding if the parents carry the normal gene. Examples of defects seen
with inbreeding include:
Reduced fertility
Reduced birth rate
Higher infant and child mortality
Smaller adult size
Reduced immune function
Increased risk of cardiovascular disease
Increased facial asymmetry
Increased risk of genetic disorders
Examples of specific genetic disorders associated with inbreeding include
schizophrenia, limb malformation, blindness, congenital heart disease,
and neonatal diabetes.
The House of Habsburg may be the best example of the effects of
inbreeding in humans. The Spanish Habsburg dynasty endured for six
centuries, largely from consanguineous marriages. The last ruler of the
line, Charles II of Spain, displayed a number of physical problems and was
unable to produce an heir. Experts believe inbreeding lead to
the extinction of the royal line.