LEC # 7
the human genome
MODEL ORGANISMS
Genes with same function in different organisms tend to
be similar or identical in structure and nucleotide
sequence.
Model Organism
 Organisms (non-human species) used for the
study of biological processes
 Show facts or principles that are relevant to an
entire domain of life
 They are often small, have short generation time,
easy to work with in large numbers and cheap to
maintain, produce many offspring
 Used to study human diseases
 EX: DNA Recombinant Technology – models of
human diseases such as bacteria, plants, animals
Prokaryotes (Bacteria)
 Escherichia coli is the classical model of
molecular biology
 It is used to study transcription, translation,
recombination, DNA repair and gene regulation
 Easy to grow; divides every 20 minutes
Yeast
 Baker’s yeast (Saccharomyces cerevisiae) was the
first eukaryote genome to be fully sequences
 Yeasts are useful organism for the study of basic
eukaryotic phenomena (cell cycle regulation,
metabolism, protein folding, and DNA repair)
 More related to animals than plants
 Study of human cells
 Chief limitation is the lack of distinct tissues
Caenorhabditis elegans
 It was chosen as a model organisms for its
simplicity and experimental tractability, with the
initial interest in the development of the nervous
system
 First multicellular organism with its complete
genome sequenced
 Rapid life cycle – egg to adult  3 days
 Cell fertilizing hermaphrodite
 Invariant number of somatic cells; do not divide
 Adult hermaphrodite  302 neuron
 Practafit every cell
 38% of its protein encoding gene has orthologs in
 Forward and reverse genetic have led to the
molecular identification of many genes in
developmental and cell biological process
 Forward genetics – study of phenotype  find
genes that is responsible for particular phenotype
 Reverse genetics – genes and genetic sequence is
known but you need to find its function and how
it affects phenotype
 It is transparent so individual cells are easily
visualized
Fruit Fly
 Drosophila melanogaster is a model used to
study several human diseases
 Extensively used in biomedical research
 Mutant genes identified in the fruit fly that
produce abnormalities of the nervous system
have been found to have human counterparts
 Utilized for the transfer of mutant human disease
genes using recombinant DNA technology
 The manipulability of its genetic system and its
comparable biological complexity to mammals
make it a good model organism
 Provided new insights into cancer,
neurodegenerative diseases, behavior, immunity,
aging and development
Zebrafish (Danio rerio)
 Vertebrate systems such as the zebrafish provide
an accurate model for human disease conditions
 Small and cheaper to maintain than mice
 The embryos are nearly transparent which allows
the observation of the development of internal
structures
 Eggs are fertilized outside the mother’s body,
thus useful for studying early development
 Similar genetic structure to humans
 Has the same major organs and tissues as
humans
 Muscle, blood, kidney and eyes share many
features with human system
Chick Embryo
 Contributed to the knowledge of the immune
system, virology, cell biology, cancer and genetics
 They are used to study development
 Embryo can easily be seen
 expression by
Mouse interfering with
 Used to study aspects of human biology and translation to not be
a protein product
medicine
 Fast generation time
 Closest mammalian model organism to humans
 Transgenic animals
 The advantage of the mouse system is the ability easily generated
to make targeted gene knockouts  Mosaic analysis
 Gene knockouts – utilized during reverse genetic; Zebrafish  Simplest vertebrate  Cannot easily
gene will be rendered non functional  effect on with good genetics make
phenotype  Easy examination of transgenic
morphological animals
 Rats (Rattus norvegicus) was once the animal of
defects (clear
choice decades ago but became unpopular
embryos)
because its genome cannot tolerate insertion of  Embryological
foreign DNA near the extent of the mouse manipulations
genome possible
 Organ systems
Arabidopsis thaliana similar to other
vertebrates (eyes,
 Commonly known as thale cress
heart, blood, GIT)
 A sophisticated model for the plant kingdom  Rapid vertebrate
 Small size, easy genetics, and with prolific seed development
production through self pollination Chicken  Availability, low cost  Limited
 Recognized because of its small genome  Accessibility, genome data
outside of mother at present
 Well suited for
Advantages and Limitations of some Model
embryological
Organisms manipulation
 Easily transfected by
Organism Advantages Disadvantages
avian retroviruses -
Yeast  Excellent genetics  No distinct
virology
 Genes can be easily tissues
Mouse  Mammal with brains  Forward
cloned
similar to human genetics
 Genome sequence
 Reverse genetics difficult
complete
 Developmental  Embryonic
 Possess all basic
overview is same for manipulations
eukaryotic
all mammals difficult (inside
organelles
 Construction of mother)
 Cell cycle control
chimeric embryos  Development
similar to animals
possible and life cycle
Nematode  Excellent genetics  Limited
 Availability of relatively slow
 Hermaphrodites external
material at all stages (months)
 RNAi effective morphology
 Source of primary
 Genome sequence  Less similar to
cells for culture
complete human than
Humans  Many diseases, self-  Fetal material
 Few cells: 959 cells, flies
reporting mutants difficult
302 neurons  Some
 Some good family  No
 All cell lineages are embryological
pedigrees experimental
known manipulations
 Genome sequence access
difficult
complete
Fruit fly  Genome sequence  Embryological
complete manipulations
 RNAi effective – difficult
RNA interference =
down regulate gene