Biology Reference
In-Depth Information
Molecular Markers
DNA consists of two strands connected by “rungs” of complementary bases (i.e., it is
double stranded). Each strand contains approximately 3 billion bases. If we consider the total
number of bases contained in both strands, the count doubles to 6 billion.
Probably within the next five to ten years, it will be possible to analyze all 6 billion bases
contained within a single human individual's genome at once. However, at present, both cost
and technology are limiting factors, so we take shortcuts to obtaining genetic information by
targeting molecular
markers
instead. A “marker” is any informative region of the genome
that is either nonprotein coding and therefore selectively neutral, or is protein coding and
therefore potentially subject to selection. The particular research interests dictate whether
or not any particular region of the genome is informative, and therefore if it may qualify
as a “marker.”
Currently, researchers regularly utilize three types of markers
dSNPs
,
STRs
, and more
rarely,
elementsd
each of which will be explained further in this section. Though the
human genome literally consists of linear arrays of bases arranged into chromosomes, this
doesn't mean that all genomic regions behave in the same way, or that they impart the
same kind of information. Some genomic sites develop mutational changes frequently (i.e.,
from one generation to the next) and others do not; the difference has to do with the biochem-
istry of the genomic regions themselves. Some genomic regions even contain molecular tools
to virtually “cut and paste” themselves from one part of the genome to another!
Alu
SINGLE NUCLEOTIDE POLYMORPHISM (SNP)
The simplest form of genetic variant is a
S
ingle
N
ucleotide
P
olymorphism, or SNP
(pronounced “snip”). An SNP is a difference in a single base in a particular location on the
genome (i.e., at a particular nucleotide position). At the moment, researchers are not inter-
ested in
unique
SNPs (those present only in a single or in a very few individuals) precisely
because they cannot be used to provide information about any random individual drawn
from a population sample. This may change as the cost of obtaining and storing information
on whole genomes decreases.
SNPs can take one of three forms: a single base change (for example, some individuals
have an A at a genomic site while others may have a C, G, or T), an insertion of base, or a dele-
tion of a base in a DNA sequence. SNPs are common throughout both nuclear and mitochon-
drial genomes.
Though they are common, the chances of a SNP developing as the result of a mutation is
low; it is estimated that an SNP will occur once in every 10
8
bases per generation (
Kruglyak,
1999
). Because it is relatively unusual for a new mutational change to occur in any particular
genomic location in an individual,
and
for it to become prevalent in a population over time,
SNPs tend to be most useful in addressing questions of long-term evolutionary significance.
For example, if researchers were to find two individuals in a population sharing an A at
a particular genomic site, we would assume that they likely share that A because at some
point back in time they shared an ancestor who had developed the “A” mutation, and not
because they both happened to develop the mutation independently.
Also, because SNP differences are so rare relative to other DNA markers, and because any
single individual will only present at most one of four possibilities at that SNP site (an A, G,
