Biomedical Engineering Reference
In-Depth Information
diploid cell assumes a quiescent but viable form, the sporal form. When surrounding
conditions get better, each spore germinates, giving origin to a vital cell. The
S.
cerevisiae
haploid genome is composed by 16 linear chromosomes, for a total of
nearly 1206 Mb, with 5570 genes coding proteins (nearly 70% of the genomic DNA).
The
S. cerevisiae
genome was the first to be sequenced completely [13]. Moreover,
the majority of the ORF (open reading frame) has been annotated, allowing for the
identification and functional characterization of the respective gene products. The
availability of the complete yeast genome sequence allowed for the construction of
mutants knocked out for every gene.
14.1.2.2 Model Characteristics
One of the most relevant advantages rising from
the use of
S. cerevisiae
as a model in high-throughput screenings is given by the
availability of its completely sequenced and almost entirely annotated genome. The
deep knowledge of the yeast genome and the relatively high efficiency of homolog
recombination facilitated the microorganism genetic manipulation, thus providing
many techniques for dissection, manipulation, and transformation of the genome.
Taking advantage of these characteristics, a wide collection of mutants has been
generated. A central role in the study of the effects of molecules and perturbations
is held by the collection composed of strains each deleted for a single gene. Such a
collection has been developed both in homozygote (encompassing deletion of only
nonessential genes) and heterozygote (composed of strains deleted for every gene
annotated) genetic backgrounds. Knowledge of
S. cerevisiae
is not restricted to its
genome but is also supported by a deep knowledge of the metabolism (both aerobic
and anaerobic). Moreover, an encouraging advantage of using
S. cerevisiae
as a model
in high-throughput screenings rises from the availability and economical affordability
of the necessary growing media and handling procedures.
S. cerevisiae
cells show high similarity with higher eukaryotic cells such as human
cells, sharing a substantial evolutionary conservation of the principal biological pro-
cesses (i.e., cell cycle, DNA reparation, several metabolic pathways). By virtue of
these characteristics, the budding yeast has been defined as an “honorary mammal”
[14]. In a recent study [15], the excellence of
S. cerevisiae
as a model organism
has been reassessed at the molecular level by full proteome comparison with several
organisms. The advent of Next-Generation Sequencing (NGS) techniques allowed
for the more rapid and accurate sequencing of complete genomes of every organism,
thus paving the way to disclosure of an almost unexplored universe of genetic and
molecular features. In their work, Karathia et al. [15] compared protein sequences
obtained by an
in silico
translation of newly sequenced genomes of several organisms
with the
S. cerevisiae
protein sequence, which is almost completely annotated. Thus,
they defined the level of conservation of the primary structure of proteins, protein
functions, and the protein pathway, giving a measure of the reliability of yeast to
model the organisms analyzed. It should be noted that the vast majority of essential
genes in
S. cerevisiae
are conserved in many other organisms and in
Homo sapiens
as well (Figure 14.2). These genes code for proteins involved in pivotal reactions
for the survival of the cells, and a malfunction in the respective human orthologs is
often associated with severe diseases [16,17]. The “honorary mammal”
S. cerevisiae
