1 Gene Geography Dan Graur Department of Biology and Biochemistry 3c

2 Gene density (genes/Kb) Mycoplasma genitalium 0.8 Escherichia coli 0.6 Saccharomyces cerevisiae0.5 Caenorhabditis elegans 0.2 Arabidopsis thaliana 0.2 Homo sapiens0.03 Alu in Homo sapiens 1.1

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

4 Periodicity in gene density along chromosome XI of Saccharomyces cerevisiae.

5 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).

6 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).

7 Genetic material Chromosomes Extrachromosomal material PlasmidsEpisomes Cryptic (linear) Giant (circular)

8 Chromosomes contain genes that are unconditionally essential. Extrachromosomal elements contain genetic information that is not necessary under all conditions.

9plasmidepisome

10Brucella =

11 Even in Bacteria chromosome number does not correlate with DNA content.

12 Classification of eukaryotic chromosomes by centromere position.

13 Gene loss

14 Gene addition

15 Gene rearrangement

16 Exchanges of genetic information between two nonhomologous chromosomes.

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

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

19 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

20 Muntiacus reevesi

21 2N = 44 + (XX or XY) 2N = 6 + (XX or XY 1 Y 2

22 Inferring the number of gene-order-rearrangement events

23 The alignment-reduction method by David Sankoff genome content deletion distance (D) = the minimal number of deletions or insertions necessary to turn genome content A into genome content B. gene order rearrangement distance (R) = the minimal number of inversions and transpositions necessary to convert gene order of A into the gene order of B.

24 evolutionary edit distance (E): E = D + R

25 To estimate E, we employ three geometrical procedures: deletion, bundling, and inversion D = 2 bundle is w/o price

R = 3

27 Tsuzumi graph Tsuzumi drum

28 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.

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

30 Sorting by reversals Nicotiana Lobelia

31 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.

32

33 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.

34 Assumption: A uniform distribution of genes over the genomeEstimate: Number of genomic disruptions required to explain the differences between two genomes.

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

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

37 Conclusions: inter intra (3) interchromosomal rearrangements occur approximately four times more frequently than intrachromosomal ones.