A short introductory presentation on Yeast Bioinformatics, focussing on the Yeast Genome and its future applications. Intended as a starting material to learn more about Saccharomyces Genomics.

1. A BASIC INTRODUCTION TO YEAST
GENOME BIOINFORMATICS
Aman Nanavaty

2. ACKNOWLEDGEMENT
I would like to thank my parents for always
supporting me and guiding me through tough times.
Without their love, support and advice, I would not be
where I am.
I wish to thank my university, Vellore Institute of
Technology (VIT Vellore) for providing me quality
education in the fields of biotechnology,
bioinformatics and related biosciences. I have gained
immeasurable knowledge as well as a fresh
perspective during my tenure here.
I would also like to thank my professor for her
constant support and expert advice. Without her
guidance and key insights, this review would not be
possible.

3. INTRODUCING YEASTS
Yeasts are eukaryotic single celled microbes that are part of the fungus
kingdom. It is estimated that the 1500 known yeasts constitute 1% of all
known fungi. Yeasts evolved from ancient multicellular organisms and
have been exploited by humans for over 5000 years. Yeasts have a typical
diameter of 3-4 micrometers, although it differs greatly among individual
yeasts. They are most notable for being able to form psuedohyphae,
strings of connected budding cells. Most yeasts reproduce via asexual
means, such as budding or spore release. In harsh, nutrient-limited
conditions, many yeasts reproduce sexually by forming meiotic spores.
Yeasts have been used for thousand of years by ancient civilisations for
wine, beer and bread. In the modern world, yeasts are used to produce
bioethanol and are added as food additives. Yeasts are
chemoorganotrophs, using organic carbon compounds as energy
sources without using sunlight. Yeasts are able to metabolise a wide
range of compounds as energy source, such as pentose sugars (ribose),
hexoses (glucose), alcohols, organic acids and disaccharides (maltose).
They are tolerant of a wide range of pH and temperature, with
Leucosporidium frigidum able to grow at a temperature of -2° C. Candida
slooffi, prefers higher temperatures above 30° C. Yeasts are found in a
variety of places, such as plant exudates (plant sap), human skin, fruit
skins (berries & apples), mammalian guts and even deep-sea
environments. In addition to performing fermentation, they can also
produce certain bioactive substances such as glutathione, glucans and
vitamins.

4. YEAST SPECIES OF
LABORATORY IMPORTANCE
1. Schizosaccharomyces pombe- Fission Yeast, extensively used as
model organism for studies on cellular processes, entire genome
sequenced
2. Saccharomyces cerevisiae- Bakers Yeast, widely used in bakeries and
breweries due to its excellent fermentation capabilities, also used as
model organism for cellular processes, entire genome sequenced
3. Cryptococcus neoformans- Pathogenic species that causes
cryptococcosis, normally resides in avian droppings, entire genome
sequenced
4. Candida albicans- opportunistic pathogen that causes Candidiasis,
often infects HIV- weakened host, part of natural skin flora, entire
genome sequenced
5. Candida glabrata- Haploid yeast species, can cause Candidiasis and
Candidemia in humans, closely related to S. cerevisiae
6. Saccharomyces paradoxus- Wild Yeast species, very closely related
to S. cerevisiae, used in phylogenetic studies to compare evolutionary
relationships with laboratory yeasts

5. CHARACTERISTICS OF THE
YEAST GENOME
While different yeasts have different genome structures, there are a few
generalisations that apply to them:
Average Genome Size of 12-20 Mb
Approximately 40% G+C content
Gene density in the range of 50-70%
Chromosome Number in the range of 8-13
4000+ ORFs
Not all yeast species have similar genomes. Schizosaccharomyces
pombe has only 3 chromosomes while Saccharomyces cerevisiae has 16
chromosomes. S. pombe has 4929 ORFs, S. cerevisiae has 6275 ORFs, K.
lactis has 5329 ORFs and A. gossypii has 4718 ORFs. S. cerevisiae has
12.1 Mb genome while K. lactis has a 10.6 Mb genome. Since yeasts have
colonised a wide range of habitats such as fruit skin, depths of the
oceans, insect guts and mammalian skin, they have been subjected to
different conditions that have uniquely shaped their genomes. This is why
yeasts found in mammalian guts are similar, but different to ones found in
insect guts.

6. WHY ARE YEASTS CHOSEN
AS MODEL ORGANISMS
Of all the 1500 known yeasts, scientists mainly use 2 yeast species as
model organisms, namely Schizosaccharomyces pombe and
Saccharomyces cerevisiae. Scientists have been able to describe many
key processes such as cell division and DNA replication by studying
these processes in S. pombe and S. cerevisiae. They have been chosen
as model organisms as their genomes are relatively small, have short
generation times and can be grown efficiently in laboratory conditions. S.
cerevisiae has a doubling time of around 2 hours, while S. pombe has a
doubling time of around 4 hours. S. pombe and S. cerevisiae diverged
from each around 300 to 600 million years ago. The ease of culturing of
these yeasts has facilitated research in the fields of genetics and
molecular biology. Cell Cycle, Cytokinesis, DNA Repair, Ageing and
Meiosis were all studied by using S. cerevisiae. Almost all of our
knowledge on eukaryotic division and replication processes comes from
research on S. pombe and S. cerevisiae. For example, the regulation of
the cell cycle in eukaryotes was elucidated by studies of cell cycle
regulators in S. pombe. Since the mechanisms of cell cycle regulation as
well as DNA repair are common in yeasts and humans, studying these
processes in yeasts can help us understand human cell cycle regulation
and DNA repair.
CELL CYCLE OF S. pombe CELL CYCLE OF S. cerevisiae

7. PROMINENT YEAST
GENOME DATABASES
The most widely-used Yeast Genome Databases are:
1. Candida Genome Database (CGD) - for Candida species
2. Saccharomyces Genome Database (SGD) - for budding yeast,
Saccharomyces cerevisiae
3. PomBase - for fission yeast, Schizosaccharomyces pombe
4. EnsemblFungi
5. PubMLST
Alternatively, details about the genomes of many yeasts such as Candida
tropicalis and Cryptococcus neoformans can be found in the National
Institute of Health (NIH) website.
Candida Genome Database (CGD) provides correct and descriptive
information on the genomes of Candida species, such as Candida
albicans and Candida auris.
PomBase is an extremely useful biological database that is renowned
worldwide. It is a complete source of quality genetic information of S.
pombe, while also being free for everyone. It stores all relevant details
such as number of genes, human homologs, etc. for quick reference.
SGD is the go-to destination for retrieving genetic information on S.
cerevisiae. It houses the complete DNA sequence, mutant phenotypes
and gene products. SGD is free and available for all.
These databases are regularly updated and refreshed in order to provide
new novel information. PomBase, in particular, is community curated and
hence stores a wide range of fresh and complete information of S. pombe
genome.

8. ROLE OF YEAST GENOME
IN RESEARCH STUDIES
Yeasts such as S. cerevisiae and S. pombe are used as model organisms
to study:
Mechanism of Cell Cycle Regulation in Eukaryotes, roles of Cyclins and
cellular checkpoints
Eukaryotic Gene Splicing
Different Pathways of DNA repair
Phases of Cell Division
Meiosis
ROS-induced chronological ageing
Telomere Function
Disease pathways in Humans
Since yeasts and humans share many common genes that are involved in
the cell cycle and meiosis, it is prudent to use yeasts as model organisms
in studies of multicellular eukaryotes. The mechanisms of gene splicing
in eukaryotes were fully described after elaborate studies on the gene
splicing in yeasts such as S. pombe and S. cerevisiae.
The Genome Project entailed the elucidation of entire fungal genomes,
mainly concentrating on yeasts. The genomes of S. pombe, C.
neoformans and S. cerevisiae were fully sequenced through elaborate
and comprehensive analytical studies.
The pathogenesis of Cryptococcus species and their effects on humans
have been described with the help of vast biological databases
specialised in yeast genomes. Even today, novel yeasts are being studied
for their potential applications in industry as well as their potential
pathogeny.

9. FUTURE APPLICATIONS
Yeasts are extremely useful organisms, serving as model organisms,
sources of crucial biochemical compounds and helping ecological
balance. Many yeasts of the Schizosaccharomyces and Saccharomyces
Genus are often used in fermentation processes involved in wineries and
breweries. The species of yeast used depends on the conditions and type
of product wanted. Individual yeasts have different optimal conditions
and hence there is no yeast that is used in all alcohol industries. By using
information from yeast genome databases such as SGD, PomBase and
EnsemblFungi, we can combine desirable traits by introducing
corresponding genes into a template yeast. Genetic Engineering is now
possible, enabling us to produce a superior yeast that thrives in all
conditions, is multi-faceted and has higher yield. By selecting suitable
genes that encode for desirable traits from the extensive online
databases, we can proceed with plasmid manipulation to produce a
superior, better GEM yeast.
By understanding the mechanisms of cell division, cell cycle regulation,
meiosis and biological ageing in yeasts, scientists are able to better
understand them in humans and design creative medical treatments that
can efficiently treat genetic disorders and cancers. Also, researchers
have been able to describe previously unknown regions of the human
genome by studying their yeast counterparts. The shared genome
similarity between yeasts and humans has enabled scientists to learn
more about cellular processes and mechanisms.
Yeasts are also being utilised in production of bio-ethanol and in
aquariums as a source of CO2. Environmental biotechnologists are also
studying the ability of yeasts to degrade harmful xenobiotics in soil and
water.

10. THANK YOU