METAGENOMICS
Metagenomics or environmental genomics or
ecogenomics or community genomics is the study
of genetic material recovered directly from
environmental samples. It is defined as the the
comprehensive study of nucleotide sequence,
structure, regulation, and function”.
Metagenomics enables studies of organisms that are
not easily cultured in a laboratory as well as studies
of organisms in their natural environment. The term
"metagenomics" was first given by Jo Handelsman.
Metagenomics is a new field combining
molecular biology and genetics in an
attempt to identify, and characterize the
genetic material from environmental
samples and apply that knowledge. The
genetic diversity is assessed by isolation of
DNA followed by direct cloning of
functional genes from the environmental
sample.
© 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458
What is Metagenomics?
Traditional microbial genomics
Sequence the genome of one organism at a time
Use cultures to isolate microbe of interest
Metagenomics
Extract sequence data from microbial
communities as they exist in nature
Bypass the need for culture techniques
Sequence all DNA in sample
Select DNA based on universal sequences
© 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458
Techniques in Metagenomics
Isolate DNA
Depends on sample
type
Clone DNA
Insert into plasmid
Develop sample library
Screen or sequence
From Figure 2 in Daniel, R. (2005) "The
Metagenomics of Soil" Nature Reviews Microbiology
3: 470-478.
Analysis of Metagenomics Data
Metagenomes are big
Soil has as many as 40,000 individual microbial species
Soil metagenome orders of magnitude bigger than
human genome
Analyzing the metagenome
Screens
Phylogenetic studies
Sequencing uncultivated organisms
Studying metagenome under different conditions
Applications
$2.3 billion in sales of industrial enzymes in
2003
Discovery of novel enzymes and catalysts with
industrial uses by screening thousands of
microbial species simultaneously
Look for pharmacologically interesting genes
(e.g. antibiotics) that exist in organisms that
cannot be cultured
© 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458
Pharmacogenetics and
Pharmacogenomics
Pharmacogenetic versus
Pharmacogenomic
No universally accepted definitions of either
Often used interchangeably
Pharmacogenetics used for more than 40 years to denote the science
about how heritability affects the response to drugs.
Pharmacogenomics is new science about how the systematic
identification of all the human genes, their products, interindividual
variation, intraindividual variation in expression and function over time
affects drug response/metabolism etc.
The term pharmacogenomics was coined in connection with the human
genome project
Most use pharmacogenetics to depict the study of single genes and their
effects on interindividual differences in (mainly) drug metabolising
enzymes, and pharmacogenomics to depict the study of not just single
genes but the functions and interactions of all genes in the genome in the
overall variability of drugs response
Pharmacogenetics
“Pharmacogenetics is the study of how
genetic variations affect the
disposition of drugs, including their
metabolism and transport and their
safety and efficacy”
J. Hoskins et. al NRC 2009
Pharmacogenetics involves both PK
and PD
Pharmacokinetic
“The process by which a drug is absorbed,
distributed, metabolized, and eliminated by the
body”
Pharmacodynamic
“the biochemical and physiological effects of
drugs and the mechanisms of their actions”
Goals of
Pharmacogen(etics)omics
Maximize drug efficacy
Minimize drug toxicity
Predict patients who will respond to
intervention
Aid in new drug development
Genomics, Proteomics and
Metabolomics
Genomics
The complete set of DNA found in each cell is
known as the genome
Most crop plant genomes have billions of
nucleotide bases
Arabidopsis thaliana has 120 million bases that
encode approximately 25,000 genes
The entire Arabidopsis genome was sequenced in
2000
Other Plant Genomes are being
sequenced
Large scale sequencing: rice, alfalfa
Grass ESTs: rice, maize, barley, wheat, millet,
sorghum, forage grasses
Dicot ESTs: alfalfa, bean, beet, cassava, cotton,
lettuce, potato, rapeseed, soybean, sunflower,
tomato, ice plant
Tree ESTs: apple, cherry, pine, poplar
Functional Genomics
Determining the role of genes through gene
disruption (knockouts, underexpression and
overexpression
Many genes have multiple copies
Proteomics
The complete set of proteins found in each cell
is known as the proteome
Approximately 25,000 proteins in a plant cell
Proteins concentration (and activity) may be
different than gene expression due to post-
translational modification
Metabolomics
The complete set of metabolites (5000 +)
found in each cell is known as the metabolome
Use high-throughput mass spectrometry to
analyze the metabolic components of the cell
Useful for determining the effects of the
environment or gene transformation on the
metabolism of the plant
Bioinformatics
The analysis of large volumes of genomic,
proteomic and metabolomic data requiring
sophisticated algorithms and powerful
computers
Rapidly evolving field with an extreme
shortage of skilled workers to write programs
and analyze data
Conclusions
Genomics, proteomics and metabolomics will
give an integrated, wholistic view of the cell
Can be used to monitor or modify organisms in
a comprehensive way
Bioinformatics will be the key to
understanding the plethora of information and
modeling the cell
