Comparative genome and proteome analysis of anopheles gambiae and drosophila melanogaster
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Comparative Genome and Proteome Analysis of Anopheles gambiae and Drosophila melanogaster.

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Comparative genome and proteome analysis of anopheles gambiae and drosophila melanogaster l.jpg

Comparative Genome andProteome Analysis of Anophelesgambiae and Drosophilamelanogaster

Evgeny M. Zdobnov, Christian von Mering, Ivica Letunic, David Torrents, Mikita Suyama, Richard R. Copley, George K. Christophides, Dana Thomasova, Robert A. Holt, G. Mani Subramanian, Hans-Michael Mueller,

George Dimopoulos, John H. Law, Michael A. Wells, Ewan Birney, Rosane Charlab, Aaron L. Halpern, Elena Kokoza, Cheryl L. Kraft, Zhongwu Lai, Suzanna Lewis, Christos Louis, Carolina Barillas-Mury, Deborah Nusskern, Gerald M. Rubin, Steven L. Salzberg, Granger G. Sutton, Pantelis Topalis, Ron Wides, Patrick Wincker, Mark Yandell, Frank H. Collins, Jose Ribeiro, William M. Gelbart, Fotis C. Kafatos, Peer Bork

Presented by Leon G Xing

SCIENCE VOL 298 4 OCTOBER 2002


Why anopheles gambiae l.jpg
Why Anopheles gambiae?

  • It is the principal vector of malaria

  • It carries many other infectious diseases

  • Malaria afflicts more than 500 million people

  • Morethan 1 million people die each year from malaria



Why drosophila melanogaster l.jpg
Why Drosophila melanogaster

  • One of the most intensively studied organisms in biology

  • Serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes

  • Modest genome size ~ 180 MB

  • Its genome has been sequenced in 2000


Mosquito vs fruit fly l.jpg
Mosquito vs. Fruit Fly

  • They diverged about 250 million years ago

  • (Human and pufferfish diverged about 450 million years ago)

  • Share considerable similarities

  • Half of the genes in both genomes

    are interpreted as orthologs

  • Average sequence identity about 56%,


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Mosquito vs. Fruit Fly

  • Anopheles genome is twice the size of Drosophila

  • Female Anopheles feeds on blood (Hematophagy), which is essential for egg development and propagation

  • Viruses and parasites use Anopheles as a vehicle for transmission


Orthologs l.jpg
Orthologs

  • Genes in different species that evolved from a common ancestral gene by speciation

  • Typically retain the same function in the course of evolution


Paralogs l.jpg
Paralogs

  • Genes related by duplication within an organism and have evolved a related but different function


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Predict the function of a new protein

  • A powerful approach is to use bioinformatics and domain database searches to find its characterized orthologs

  • We know a lot about Drosophila but don’t know much about Anopheles

  • Compare their genomes may deduce a lot of information


Drosophila melanogaster genome l.jpg
Drosophila melanogaster Genome

  • The assembled and annotated genome sequence of 5 Drosophila melanogaster chromosomes is in GenBank

  • It’s the collaboration between Celera and the Berkeley Drosophila Genome Project

  • Published in the March 24, 2000 issue of Science.



Anopheles vs drosophila gene comparison at protein level l.jpg
Anopheles vs DrosophilaGene Comparison at Protein Level

  • The proteins are classified into 4 categories based on:

    • 12,981 deduced Anopheles proteins out of 15,189 annotated transcripts

    • Omit transposon-derived bacterial like sequences, and alternative transcripts


Classification of anopheles proteins l.jpg
Classification of Anopheles proteins

  • 1:1 orthologs:

    • Anopheles proteins with one clearly identifiable counterpart in Drosophila and vice versa

    • 47% of the Anopheles

    • 44% of the Drosophila proteins


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Classification of Anopheles proteins

  • “Many-to-many” orthologs.

    • Gene duplication has occurred in one or both species after divergence

    • Includes 1779 Anopheles proteins


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Classification of Anopheles proteins

  • The third category:

    • Have homologs in Drosophila and/or other species but without easily discernable orthologous relationships

    • 3590 Anopheles predicted proteins


Classification of anopheles proteins16 l.jpg
Classification of Anopheles proteins

  • The fourth category

    • Has little or no homology in Drosophila but instead have best matches to other species.

    • 1283 proteins


Classification of anopheles proteins17 l.jpg
Classification of Anopheles proteins

  • Remaining proteins:

    • No detectable homologs in any other species with a fully sequenced genome;

    • 1437 in Anopheles

    • 2570 in Drosophila

    • Might be new or quickly evolving genes.



Some notes l.jpg
Some Notes

  • The numbers and derived estimates are approximations.

  • Annotation of genomes is an ongoing effort

  • Some Anopheles genes have not been sequenced yet

  • Highly polymorphic regions or in highly repetitive contexts prone to errors

  • > 70% accuracy


The core of conserved proteins l.jpg
The core of conserved proteins

  • The 1:1 orthologs (6089 pairs) can be considered the conserved core

  • The average sequence identity is 56%

  • Humans and pufferfish share 61%

  • Indicates that insect proteins diverge at a higher rate



Orthologous proteins constitute a core of conserved functions l.jpg
Orthologous proteins constitute a core of conserved functions

  • Early embryogenesis are conserved between Drosophila and Anopheles

  • 315 early developmental genes in Drosophila vs 251 genes showed a clear single ortholog in Anopheles


Orthologous proteins l.jpg
Orthologous proteins functions

  • 85% of the developmental genes havesingle orthologs

  • 47% for the genome as a whole


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Protein family expansions and reductions functions

  • Due to adaptations to environment and life strategies

  • Leads to changes in cellular and phenotypic features

  • Implies duplicationsafter speciation


Protein family expansions and reductions example l.jpg
Protein family expansions and reductions example functions

  • Epsilon subunit of the adenosine triphosphate-synthase complex

  • Encoded by two genes in both Anopheles and Drosophila

  • They might share a single-copy ancestral gene

  • After speciation they were duplicated independently later


Expansions of proteins with fbn like domains in anopheles l.jpg
Expansions of proteins with FBN-like domains in functionsAnopheles.

  • Fibrinogen (FBN) are found originally in human blood coagulationproteins

  • A large expansion of mosquitoproteins contains a domain resembling the COOH-terminus of thebeta and gamma chains of FBN


Expansions of proteins with fbn like domains in anopheles27 l.jpg
Expansions of proteins with FBN-like domains in functionsAnopheles.

  • Phylogenetictree of 58 Anopheles and 13 Drosophila FBN genes

  • They largely belong to two distinct species-specificclades

  • Identified only two1:1 orthologous relationships


The significant implication of fbn gene expansion l.jpg
The significant implication of FBN gene expansion functions

  • The massive expansion of the Anopheles gene FBN familymight be associated with particular aspects of the mosquito's biology

  • That is, hematophagy and exposure to Plasmodium

  • Blood meal is a challenge associated with microbial flora in the gut and blood coagulation


The implication of fbn gene expansion l.jpg
The implication of FBN gene expansion functions

  • The bacteria-bindingproperties of FBNs might be important in controllingor aggregating bacteria in the midgut

  • These proteins might be used as competitive inhibitors i.e. anticoagulants

  • Some mosquito FBN proteins are up-regulated by invading malariaparasites



Gene losses in insects l.jpg
Gene losses in insects functions

  • Some genes are absent in both Anopheles and Drosophila but are present in other eukaryotes

  • Criteria: genes must be present in at least one animal but also in fungi or plants



Gene genesis and gene loss l.jpg
Gene genesis and gene loss functions

  • 1437 predicted genes in Anopheles haveno detectable homology with genes of other species

  • 522 of thesehave putative paralogs only within Anopheles

  • At least 26of such genes expressed in the adult female salivary glands


Strategy for identifying gene losses l.jpg
Strategy for identifying gene losses functions

  • Search for genes that are present in only one of the two insects but thatdo have orthologs in other species


Gene losses l.jpg
Gene Losses functions

  • Widespread orthologs missingfrom both Anopheles and Drosophila are putativeinsect-specific gene losses

  • Example:

    • Insects are known to unable to synthesize sterols

    • Absence of severalenzymes involved in sterol metabolism


Gene losses example l.jpg
Gene Losses example functions

  • Absence of the DNA repair enzyme uracil-DNA glycosylase in insects

  • DNA methylation can lead to spontaneousdeamination of cytosine to uracil

  • Drosophila has long been known to have no or only very littleDNA methylation


Cladogram based on orthologs l.jpg
Cladogram based on functionsOrthologs


Intron gain and loss l.jpg
Intron gain and loss functions

  • Drosophila are known to have a reduction of noncoding regions

  • 11,007 outof 20,161 Anopheles introns in 1:1 orthologs have equivalent positionsin Drosophila

  • Almost 10,000 introns have either beenlost or gained


The drosophila dscam gene l.jpg
The functionsDrosophilaDscam gene

  • Able to encode up to 38,000 proteinsthrough extensive alternative splicing

  • Three different cassettes of duplicatedexons that can generate exponential combinations of splice variants

  • The numbers of exons within the cassettes are at least similarin Anopheles


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Microsynteny functions

  • Through evolution genome structure may vary greatly, but smallregions of conserved gene will be retained

  • Microsynteny studies the localized region of sequences with high similarity



Mapping of orthologs and microsynteny blocks to chromosomal arms in anopheles and drosophila l.jpg
Mapping of orthologs and microsynteny functionsblocks to chromosomal arms in Anophelesand Drosophila.


Chromosome mapping l.jpg
Chromosome mapping functions

  • Both Anopheles and Drosophila have five major chromosomal arms(X, 2L, 2R, 3L, and 3R, and a small chromosome 4 in Drosophilamelanogaster).

  • In Drosophila, reassortment of recognizablechromosomal arms occurs by fission and fusion at the centromeres


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Chromosome mapping functions

  • The most conserved pair of chromosomal arms is Dm2L and Ag3R

  • 76% of the orthologs and 95% of microsynteny blocks inDm2L mapping to Ag3R



Chromosome mapping surprise l.jpg
Chromosome mapping surprise functions

  • Significant portions of the Anopheles X chromosome appear to have been derived from what are presently autosomal Drosophilachromosome segments

  • 11% of Dm3R and33% of Dm4



Thank you l.jpg

Thank you! functions