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