Biology Reference
In-Depth Information
3. RISING ABOVE THE LIMITATIONS
3.1. Genomics
A major cause of the above limitations was that there existed no complete
understanding of inventory of all the components of a living cell, even though
such an inventory had been identified in principle, i.e. the DNA: the DNA
contains the information for all the proteins in the cell and the proteins catalyse
all the reactions. It was thought that in principle, the sequence of the DNA
should determine everything that happens in the living cell, under any given set
of environmental conditions. It became quite important therefore to sequence
all the DNA of a living organism, and in the 1990s of the previous century,
large consortia of researchers embarked on accomplishing this aim in activities
referred to as 'genomics'. It may seem that genomics was not much different
from the molecular biology that preceded it. Indeed, many of the most active
scientists in genomics continued to be molecular biologists as well. Yet, for
our discussion here, the transition between molecular biology and genomics
has been quintessential. Genomics went after the determination of the complete
DNA sequence of an organism, rather than of DNA sequence of many of its
components, i.e. genomics went for the system rather than for its components.
By 1995, the first complete sequences of the genomes of free-living organisms
(cf mitochondria in 1981 (Anderson et al., 1981)) became available (Fleischmann
et al., 1995), and importantly also the sequences of the two best-known model
organisms soon followed, i.e. the eukaryote yeast (Goffeau et al., 1996) and
the bacterium
Escherichia coli
(
E. coli
) (Blattner et al., 1997). By 2001, the
DNA sequence of humans was nominally established and sequences of many
organisms have become known as we write this. In essence, the DNA sequence
of any organism can now be determined. Because of the homology discussed
above and thanks to bioinformatics, the function of many genes can be proposed
with appreciable success rates when the homology to genes of known function
is close. Although for half of all sequenced genes (this fraction differs between
organisms), the function is uncertain or unclear, this fraction is considered to
be on the decrease. (We would stress, of course, that many genes with some
'known' functions will turn out to have other functions that are as yet unknown.)
Knowing most of the genes of an organism provided a strong motivation for
what has been called 'functional genomics', i.e. for determining whether those
genes function in terms of being expressed and what their role is. Because of
the strong tendency of nucleic acids of complementary sequence to react with
each other, this was possible in principle by making populations of small RNA
molecules each of which was complementary to part of one of all the genes in
the genome. A breakthrough came when those probe molecules could be spotted
as an array onto a slide and could be provided with a fluorescent tag that lights
up when an mRNA molecule hybridized. This nucleotide array technology is
