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COMPARATIVE
GENOMICS
Presenting by;
Shahbaz.
Government College University Faisalabad.
GENOMICS
■ The study of genome of an organism is called genomics.
In the field of molecular biology and genetics genome is the
genetic material of an organism.
It basically involve analysis of nucleotide sequence of genomes
using computational methods (sequencing of genome).
IMPORTANCE OF GENOMICS
Provides a map of the genetic make up of a cell.
• Gives an idea of how the cell responds at the
genetic level to different situations.
•This enables researchers to compare the
genomes of different organisms, to see how the
genes function in different circumstances, how
they interact, how they control over one another
or how differences in the genomes are reflected
in the phenotype.
BROAD COVERAGE OF GENOMICS
Structural genomics: Understanding the
content of genome and is concerned with
genome mapping, genome sequencing and
genome manipulations.
• Functional genomics: Identification of genes
and their respective functions
• Comparative genomics: Analysis and
comparison of genomes from different
species. It includes animal genomics, plant
genomics, microbial genomics etc..
WHAT IS COMPARATIVE GENOMICS?
Analyzing & comparing genetic material from different species
to study
■ evolution, gene function, and inherited disease
■ Understand the uniqueness between different species
Introduction
Comparative genomics is a large-scale, holistic approach that
compares two or more genomes to discover the similarities and
differences between the genomes and to study the biology of
the individual genomes
Continue…
 The subject of comparative genomics impinges on
■ – Evolutionary biology and phylogenetic reconstructions of the tree of
life,
■ – Drug discovery programs,
■ – Function predictions of hypothetical proteins
■ – Identification of genes, regulatory motifs and other non-coding DNA
■ motifs
■ – Genome flux and dynamics
WHYWE MAKE COMPARISON
■ Comparative genomics is a field of biological research in
which the genome sequences of different species —human,
mouse, and a wide variety of other organisms from bacteria
to chimpanzees — are compared.
■ By comparing the sequences of genomes of different
organisms, researchers can understand what, at the
molecular level, distinguishes different life forms from each
other.
WhyThis Comparison?
■ Comparison of whole genome sequences provides a highly
detailed view of how organisms are related to each other at
the genetic level. How are genomes compared and what can
these findings tell us about how the overall structure of genes
and genomes have evolved?
Continue…
■ Comparative genomics also provides a powerful tool for
studying evolutionary changes among organisms, helping to
identify genes that are conserved or common among species,
as well as genes that give each organism its unique
characteristics.
Muhammad Irfan please come, and
Proceed
HOW ARE GENOMES COMPARED?
A simple comparison of the general features of genomes such as
■ genome size,
■ number of genes, and
■ chromosome number presents an entry point into
comparative genomic analysis
WHAT IS COMPARED?
■ Gene location
■ Gene structure
 Exon number
 Exon lengths
 Intron lengths
 Sequence similarity
■ Gene characteristics
 Splice sites
 Codon usage
 Conserved synteny
Related terms..
■ Homology
■ Homologous
■ Orthologous
■ Paralogous
■ Xenologous
■ Analogoues
■ Horizontal gene transfer
RelatedTerms
 Homology is the relationship of any two characters (such as
two proteins that have similar sequences) that have
descended, usually through divergence, from a common
ancestral character
 Homologues are thus components or characters (such as
genes/proteins with similar sequences) that can be attributed
to a common ancestor of the two organisms during evolution.
Homologues can either be orthologues, paralogues, or
xenologues.
Continue…
Orthologues are homologues that have evolved from a common ancestral
gene by speciation.They usually have similar functions.
Paralogues are homologues that are related or produced by duplication
within a genome.They often have evolved to perform different functions.
Xenologues are homologues that are related by an interspecies
(horizontal transfer) of the genetic material for one of the homologues
Horizontal (Lateral) GeneTransfer is the movement of genetic material
between species (or genus) other than by vertical descent.
The Rest of the topic will present
Shehbaz
Methods for comparative genomics
1. Comparative analysis of genome structure
2. Comparative analysis of coding regions
3. Comparative analysis of non-coding regions
Comparative analysis of genome
structure
A. Analysis of the global structure of genomes, such as nucleotide
composition, and gene ordering offer insight
into the similarities and differences between genomes.
This provide information on the organization and evolution of the
genomes, and highlight the unique features of individual genomes
B. The structure of different genomes can be compared at three levels:
– Overall nucleotide statistics,
– Genome structure at DNA level.
Comparison of overall nucleotide
statistics
 Overall nucleotide statistics, such as
– Genome size,
– Overall (G+C) content,
– Regions of different (G+C) content,
– Genome signature such as codon usage biases,
– Amino acid usage biases, and the ratio of observed dinucleotide
frequency and
–The expected frequency given random nucleotide
distribution.
Comparison of genome structure at DNA
level
Chromosomal breakage and exchange of chromosomal
fragments are common mode of gene evolution.They can be
studied by comparing genome structures at DNA level.
– Identification of conserved regions and genome rearrangement events
– Analysis of breakpoints
– Analysis of content and distribution of DNA repeats
Comparison of genome structure at
gene level
Chromosomal breakage and exchange of chromosomal
fragments cause disruption of gene orderTherefore gene order
correlates with evolutionary distance between genomes
Comparative analysis of coding regions
I. Identification of gene-coding regions
II. comparison of gene content
III. comparison of protein content
IV. Comparative genome based function prediction
Number of algorithms that have been use in comparative
genomics to aid function prediction of genes.
Comparative Genomics in Drug
Discovery
1. Comparative genomic studies throw important light on the
pathogenesis of organisms, throwing up opportunities for
therapeutic intervention as well as help in understanding and
identifying disease genes
2. One of the most important fallouts of comparative analyses at a
genome-wide scale is in the ability to identify and develop novel
drug targets
Continue…
3. If one is looking for antibacterial, antifungal, or antiprotozoal
proteins to be used as targets, comparative genome analysis can
reveal virulence genes, uncharacterized essential genes, species-specific
genes, organism-specific genes, while ensuring that the
chosen genes have no homologues in humans
Looking Beyond…
 As comparative genomics moves from between kingdoms to
between genus to between species analysis, the next step is to
carry out comparisons between individuals or strains that are
members of a particular species
 This would allow us to investigate variations at the individual
level and to enable one to determine the propensity of an
individual to respond to a drug or to come down with a disease
or infection
IMPACT OF COMPARATIVE GENOMICS
The impact of comparative genomics will be far reaching.
For example: "The genomic revolution is
having a tremendous impact on the study of natural
variation.
This will not only help us understand biology better, but aid in our
exploitation of natural diversity for
crop improvement,
 plant breeding efforts and
 biodiversity conservation.
 These are all important to the quality of life on earth.
Comparative genomics 2

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Comparative genomics 2

  • 2. GENOMICS ■ The study of genome of an organism is called genomics. In the field of molecular biology and genetics genome is the genetic material of an organism. It basically involve analysis of nucleotide sequence of genomes using computational methods (sequencing of genome).
  • 3. IMPORTANCE OF GENOMICS Provides a map of the genetic make up of a cell. • Gives an idea of how the cell responds at the genetic level to different situations. •This enables researchers to compare the genomes of different organisms, to see how the genes function in different circumstances, how they interact, how they control over one another or how differences in the genomes are reflected in the phenotype.
  • 4. BROAD COVERAGE OF GENOMICS Structural genomics: Understanding the content of genome and is concerned with genome mapping, genome sequencing and genome manipulations. • Functional genomics: Identification of genes and their respective functions • Comparative genomics: Analysis and comparison of genomes from different species. It includes animal genomics, plant genomics, microbial genomics etc..
  • 5. WHAT IS COMPARATIVE GENOMICS? Analyzing & comparing genetic material from different species to study ■ evolution, gene function, and inherited disease ■ Understand the uniqueness between different species
  • 6. Introduction Comparative genomics is a large-scale, holistic approach that compares two or more genomes to discover the similarities and differences between the genomes and to study the biology of the individual genomes
  • 7. Continue…  The subject of comparative genomics impinges on ■ – Evolutionary biology and phylogenetic reconstructions of the tree of life, ■ – Drug discovery programs, ■ – Function predictions of hypothetical proteins ■ – Identification of genes, regulatory motifs and other non-coding DNA ■ motifs ■ – Genome flux and dynamics
  • 8. WHYWE MAKE COMPARISON ■ Comparative genomics is a field of biological research in which the genome sequences of different species —human, mouse, and a wide variety of other organisms from bacteria to chimpanzees — are compared. ■ By comparing the sequences of genomes of different organisms, researchers can understand what, at the molecular level, distinguishes different life forms from each other.
  • 9. WhyThis Comparison? ■ Comparison of whole genome sequences provides a highly detailed view of how organisms are related to each other at the genetic level. How are genomes compared and what can these findings tell us about how the overall structure of genes and genomes have evolved?
  • 10. Continue… ■ Comparative genomics also provides a powerful tool for studying evolutionary changes among organisms, helping to identify genes that are conserved or common among species, as well as genes that give each organism its unique characteristics.
  • 11. Muhammad Irfan please come, and Proceed
  • 12. HOW ARE GENOMES COMPARED? A simple comparison of the general features of genomes such as ■ genome size, ■ number of genes, and ■ chromosome number presents an entry point into comparative genomic analysis
  • 13. WHAT IS COMPARED? ■ Gene location ■ Gene structure  Exon number  Exon lengths  Intron lengths  Sequence similarity ■ Gene characteristics  Splice sites  Codon usage  Conserved synteny
  • 14.
  • 15. Related terms.. ■ Homology ■ Homologous ■ Orthologous ■ Paralogous ■ Xenologous ■ Analogoues ■ Horizontal gene transfer
  • 16. RelatedTerms  Homology is the relationship of any two characters (such as two proteins that have similar sequences) that have descended, usually through divergence, from a common ancestral character  Homologues are thus components or characters (such as genes/proteins with similar sequences) that can be attributed to a common ancestor of the two organisms during evolution. Homologues can either be orthologues, paralogues, or xenologues.
  • 17. Continue… Orthologues are homologues that have evolved from a common ancestral gene by speciation.They usually have similar functions. Paralogues are homologues that are related or produced by duplication within a genome.They often have evolved to perform different functions. Xenologues are homologues that are related by an interspecies (horizontal transfer) of the genetic material for one of the homologues Horizontal (Lateral) GeneTransfer is the movement of genetic material between species (or genus) other than by vertical descent.
  • 18. The Rest of the topic will present Shehbaz
  • 19. Methods for comparative genomics 1. Comparative analysis of genome structure 2. Comparative analysis of coding regions 3. Comparative analysis of non-coding regions
  • 20. Comparative analysis of genome structure A. Analysis of the global structure of genomes, such as nucleotide composition, and gene ordering offer insight into the similarities and differences between genomes. This provide information on the organization and evolution of the genomes, and highlight the unique features of individual genomes B. The structure of different genomes can be compared at three levels: – Overall nucleotide statistics, – Genome structure at DNA level.
  • 21. Comparison of overall nucleotide statistics  Overall nucleotide statistics, such as – Genome size, – Overall (G+C) content, – Regions of different (G+C) content, – Genome signature such as codon usage biases, – Amino acid usage biases, and the ratio of observed dinucleotide frequency and –The expected frequency given random nucleotide distribution.
  • 22. Comparison of genome structure at DNA level Chromosomal breakage and exchange of chromosomal fragments are common mode of gene evolution.They can be studied by comparing genome structures at DNA level. – Identification of conserved regions and genome rearrangement events – Analysis of breakpoints – Analysis of content and distribution of DNA repeats
  • 23. Comparison of genome structure at gene level Chromosomal breakage and exchange of chromosomal fragments cause disruption of gene orderTherefore gene order correlates with evolutionary distance between genomes
  • 24. Comparative analysis of coding regions I. Identification of gene-coding regions II. comparison of gene content III. comparison of protein content IV. Comparative genome based function prediction Number of algorithms that have been use in comparative genomics to aid function prediction of genes.
  • 25. Comparative Genomics in Drug Discovery 1. Comparative genomic studies throw important light on the pathogenesis of organisms, throwing up opportunities for therapeutic intervention as well as help in understanding and identifying disease genes 2. One of the most important fallouts of comparative analyses at a genome-wide scale is in the ability to identify and develop novel drug targets
  • 26. Continue… 3. If one is looking for antibacterial, antifungal, or antiprotozoal proteins to be used as targets, comparative genome analysis can reveal virulence genes, uncharacterized essential genes, species-specific genes, organism-specific genes, while ensuring that the chosen genes have no homologues in humans
  • 27. Looking Beyond…  As comparative genomics moves from between kingdoms to between genus to between species analysis, the next step is to carry out comparisons between individuals or strains that are members of a particular species  This would allow us to investigate variations at the individual level and to enable one to determine the propensity of an individual to respond to a drug or to come down with a disease or infection
  • 28. IMPACT OF COMPARATIVE GENOMICS The impact of comparative genomics will be far reaching. For example: "The genomic revolution is having a tremendous impact on the study of natural variation. This will not only help us understand biology better, but aid in our exploitation of natural diversity for crop improvement,  plant breeding efforts and  biodiversity conservation.  These are all important to the quality of life on earth.