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Gene GeographyGene Geography

Dan GraurDan GraurDepartment of Biology and BiochemistryDepartment of Biology and Biochemistry

3c

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Gene density (genes/Kb)Mycoplasma genitalium 0.8 Escherichia coli 0.6 Saccharomyces cerevisiae 0.5 Caenorhabditis elegans 0.2 Arabidopsis thaliana 0.2 Homo sapiens 0.03 Alu in Homo sapiens 1.1

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Genes are distributed evenly among the 16 chromosomes of Saccharomyces cerevisiae.

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Periodicity in gene density along chromosome XI of Saccharomyces cerevisiae.

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In large plant genomes, most protein-coding genes are clustered in long DNA segments (gene space, urban aggregations) that represent a small fraction (12-24%) of the nuclear genome, and which are separated from one another by vast expanses of gene-empty regions (deserts).

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Only ~1/3 genes in eukaryotes are essential for viability. The proportion does not vary much between organisms (25-35%).

• Organisms with a large number of genes (e.g., humans, fish).• Organisms with an intermediate number of genes (nematodes, Drosophila).• Organisms with a low gene number (e.g., yeast).

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Genetic material

ChromosomesExtrachromosomal

material

Plasmids Episomes

Cryptic(linear)

Giant(circular)

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Chromosomes Chromosomes contain genes contain genes that are that are unconditionallunconditionallyy essentialessential. .

Extrachromosomal elementsExtrachromosomal elements contain genetic information contain genetic information that is that is not necessarnot necessaryy under all under all conditionsconditions. .

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plasmidplasmid

episomeepisome

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BrucellaBrucella

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22 11

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==

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Even in BacteriaEven in Bacteriachromosome number chromosome number does notdoes not correlate correlate with DNA content.with DNA content.

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Classification of eukaryotic chromosomes by centromere position.

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Gene lossGene loss

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Gene additionGene addition

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Gene rearrangementGene rearrangement

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Exchanges of genetic information between two nonhomologous chromosomes.

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Mouse-human synteny.Mouse-human synteny. Human chromosomes Human chromosomes can be cut into a relatively small number pieces, can be cut into a relatively small number pieces, then shuffled into a reasonable approximation of then shuffled into a reasonable approximation of the mouse genome. the mouse genome.

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Regions of conserved synteny between human chromosome 22 and the mouse genome.

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Chromosome-number reduction

Chinese water deer (Hydropotes inermis) n = 70

Brown-brocket deer (Mazama gouazoubira) n = 70

Chinese muntjac (Munitacus reevesi) n = 46

Black muntjac (M. muntiacus crinifrons) n = 8

Indian muntjac (M. muntiacus vaginalis) n = 6

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Muntiacus reevesi

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2N = 44 + (XX or XY)

2N = 6 + (XX or XY1Y2

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Inferring the number of Inferring the number of gene-order-rearrangement gene-order-rearrangement

events events

1 2 3 4 5

3 2 5 4 5

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The alignment-reduction methodby

David Sankoff

deletion distance (D) = the minimal number of deletions or insertions necessary to turn genome contentgenome content A into genome content B.

rearrangement distance (R) = the minimal number of inversions and transpositions necessary to convert gene ordergene order of A into the gene order of B.

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evolutionary edit distance (E):

E = D + R

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To estimate E, we employ three geometrical procedures: deletion, bundling, and inversion

D = 2bundle is w/o price

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1 2 3 4 5

3 2 5 4 5

R = 3

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Tsuzumi graph Tsuzumi drum

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The conserved S10 region. The three arrows represent operons in E. coli. A dot () indicates the existence of a gene at a site; a minus sign (–) indicates that the gene has been translocated elsewhere in the genome; indicates that the gene was not found in the genome.

L and S = large and small ribosomal-proteins; prlA = preprotein-translocation secY subunit; adk = adenylate kinase; map = methionine aminopeptidase; infA = initiation-factor 1; rpoA = DNA-directed RNA-polymerase chain.

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OTUsa Hs Gg Sp Ap Po Dy As

Hs 1 18 16 19 13 25

Gg 0 19 17 17 12 26

Sp 0 0 2 1 26 27

Ap 4 4 4 1 22 25

Po 1 1 1 5 23 24

Dy 0 0 0 4 1 28

As 1 1 1 5 2 1

Evolutionary-edit distance between pairs of animal mitochondria. Rearrangement distances and deletion distances are above and below the diagonal, respectively.

aHs = Homo sapiens; Gg = Gallus gallus; Sp = Strongylocentrotus purpuratus (sea urchin); Ap = Asterina pectinifera (starfish); Po = Pisaster ochraceus (starfish); Dy = Drosophila yakuba; As = Ascaris suum (pig roundworm).

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Sorting by reversals

Nicotiana

Lobelia

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Synteny = occurrence of two or more genes on the same chromosome.

Conserved synteny = synteny of two or more homologous genes in two species.

Conserved linkage = conservation of both synteny and gene order of homologous genes between species.

Disrupted synteny = a pair of genes are syntenic in one species but their orthologs are located on different chromosomes in the second species.

Disrupted linkage = a difference in gene order between the species.

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Empirical variables:

(1) number of conserved syntenies(2) distribution of number of genes

among conserved syntenies(3) number of conserved linkages(4) distribution of number of genes

among conserved linkages.

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Assumption:Assumption:

A uniform distribution of genes over the genome

Estimate:Estimate:

Number of genomic disruptions required to explain the differences between two genomes.

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Conclusions:

(1) gene-order rearrangements occur at high rates.

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Conclusions:

(2) rates of synteny disruption vary widely among mammalian lineages.The mouse lineage has a rate of The mouse lineage has a rate of synteny disruptions that is 25 times synteny disruptions that is 25 times higher than that of the cat lineage.higher than that of the cat lineage.

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Conclusions:

(3) interinterchromosomal rearrangements occur approximately four times more frequently than intraintrachromosomal ones.