1. 1 Genome Evolution Chapter 24

2. 2 Introduction Genomes contain the raw material for evolution Comparing whole genomes enhances – Our ability to understand evolution –To improve crops –To identify genetic basis of disease

3. 3 Comparative Genomics Making the connection between a specific change in a gene and a modification in a morphological character is difficult Genomes carry information on the history of life Evolutionary differences accumulate over long periods

4. 4 Genomes of viruses and bacteria evolve in a matter of days Complex eukaryotic species evolve over millions of years Example: tiger pufferfish (Fugu rubripes), mouse (Mus musculus), and human genomes Comparative Genomics

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8. 8 Comparison between human and pufferfish genomes –Last shared common ancestor 450 MYA –25% human genes no counterparts in Fugu –Extensive genome rearrangements since mammal lineage and teleost fish diverged Comparative Genomics

9. 9 –Human genome is 97% repetitive DNA –Repetitive DNA less than 1/6 th Fugu genome sequence Comparative Genomics

10. 10 Human and mouse genomes –Human: 400 million more nucleotides than the mouse –25,000 genes and they share 99% –Diverged about 75 MYA –300 genes unique to either organism (1%) –Rearrangements of chromosomal regions large and small Comparative Genomics

11. 11 Human and chimpanzee genomes –Diverged 35 MYA –1.06% of the two genomes have fixed differences in single nucleotides –1.5% difference in insertions and deletions –53 of human-specific indels lead to loss- of-function changes Comparative Genomics

12. 12 –Smaller ratio in nonsynonymous to synonymous changes –Purifying selection: removal of nonsynonymous genes Comparative Genomics

13. 13 Genomes evolve at different rates Mouse DNA has mutated twice as fast as human Fruit fly and mosquito evolve more rapidly than vertebrates Difference in generation time accounts for different rates of genome evolution Comparative Genomics

14. 14 Plant, fungal, and animal genomes have unique and shared genes –Animal genomes are highly conserved –Plant genomes are highly conserved Comparative Genomics

15. 15 Comparison between two plant genomes –Arabidopsis thaliana (mustard family plant) 25,948 genes; 125 million base pairs –Rice (Oryza sativa) 430 million base pairs –Share 80% of genes Comparative Genomics

16. 16 Comparison of plants with animals and fungi –1/3 rd genes in Arabidopsis and rice “plant” genes: distinguish plant kingdom from animal kingdom Comparative Genomics

17. 17 –Remaining genes similar to genes found in animal and fungal genomes Basic intermediary metabolism Genome replication and repair RNA transcription & protein synthesis Comparative Genomics

18. 18 Evolution of Whole Genomes Polyploidy can result from –Genome duplication in one species –Hybridization of two different species Autopolyploids: genome of one species is duplicated through a meiotic error –Four copies of each chromosome Allopolyploids: result from hybridization and duplication of the genomes of two different species

19. 19 Evolution of Whole Genomes

20. 20 Evolutionary history of wheat Evolution of Whole Genomes

21. 21 Ancient and newly created polyploids guide studies of genome evolution –Two avenues of research Paleopolyploids: comparisons of polyploidy events –Sequence divergence between homologues –Presence or absence of duplicated gene pairs from hybridization Evolution of Whole Genomes

22. 22 –Two avenues of research cont’d Synthetic polyploids: crossing plants most closely related to ancestral species and chemically inducing chromosome doubling Evolution of Whole Genomes

23. 23 Plant polyploidy is ubiquitous, with multiple common origins Comparison of soybean, forage legume, and garden pea shows a huge difference in genome size Some genomes increased, some decreased in size Polyploidy induces elimination of duplicated genes Evolution of Whole Genomes

24. 24 Polyploidy has occurred numerous times in the evolution of flowering plants Evolution of Whole Genomes

25. 25 Genome downsizing Evolution of Whole Genomes

26. 26 Polyploidy may be followed by the unequal loss of duplicate genes from the combined genomes Evolution of Whole Genomes

27. 27 Transposons jump around following polyploidization –Barbara McClintock (Nobel Prize) –Controlling elements: jumping DNA regions –Respond to genome shock and jump into a new position –New phenotypes could emerge Evolution of Whole Genomes

28. 28 –New transposon insertions occur because of unusually active transposition –New insertions could cause Gene mutations Changes in gene expression Chromosomal rearrangements Evolution of Whole Genomes

29. 29 Aneuploidy: duplication or loss of an individual chromosome Plants are able to tolerate aneuploidy better than animals Duplication of segments of DNA is one of the greatest sources of novel traits Evolution Within Genomes duplicationloss

30. 30 Fates of duplicate gene: –Losing function through mutation –Gaining a novel function through mutation –Having total function partitioned into the two duplicates Evolution Within Genomes

31. 31 Segmental duplication on the human Y chromosome Evolution Within Genomes

32. 32 Gene duplication in humans is most likely to occur in three most gene-rich chromosomes –Growth and development genes –Immune system genes –Cell-surface receptor genes Evolution Within Genomes

33. 33 5% of human genome consists of segmental duplications Duplicated genes have different patterns of gene expression Rates of duplication vary for different groups of organisms Evolution Within Genomes

34. 34 Drosophila –31 new duplicates per genome per million years (0.0023 duplications per gene per million years) –C. elegans 10 times fast rate Paralogues: two genes within an organism that have arisen from duplication of a single gene in an ancestor Orthologues: conservation of a single gene from a common ancestor Evolution Within Genomes

35. 35 Genome reorganization Humans have 1 fewer chromosome than chimpanzees, gorillas, and orangutans Fusion of two genes into one gene; chromosome 2 in humans Chromosomal rearrangements in mouse ancestors have occurred at twice the rate seen in humans Evolution Within Genomes

36. 36 Chromosomal rearrangement Evolution Within Genomes

37. 37 Variation in genomes Conservation of synteny: the preservation over evolutionary time of arrangements of DNA segments in related species –Long segments of chromosomes in mice and humans are the same –Allows researchers to locate a gene in a different species using information about synteny Evolution Within Genomes

38. 38 Synteny and gene identification Soybean M. truncatula d2Kc2b2c1 2 3 Evolution Within Genomes

39. 39 Gene inactivation results in pseudogenes Loss of gene function: way for genomes to evolve –Olfactory receptor (OR) genes: inactivation best explanation for our reduced sense of smell –Primate genomes: > 1000 copies of OR genes Evolution Within Genomes

40. 40 Pseudogenes: sequences of DNA that are similar to functional genes but do not function –70% of human OR genes are inactive pseudogenes –>50% gorilla & chimpanzee OR genes function –>95% New World monkey OR genes work well Evolution Within Genomes

41. 41 Active genes Pseudogenes Nonolfactory DNA Human olfactory gene cluster (chromosome 17) Chimpanzee olfactory gene cluster (chromosome 19) Gene inactivation Evolution Within Genomes

42. 42 Chimp genome analysis –Indicated both humans and chimps are gradually losing OR genes to pseudogenes –No evidence for positive selection for any OR genes in chimps Vertical gene transfer (VGT): genes are passed from generation to generation Evolution Within Genomes

43. 43 Horizontal gene transfer (HGT): genes hitchhike from other species –Can lead to phylogenetic complexity Evolution Within Genomes

44. 44 HGT continues today Phylogenies build with rRNA sequences: Archaea more closely related to Eukarya than to Bacteria Organisms swapped genes Find organisms with both Archaea and Bacteria genes Perhaps tree of life is more of a web than a branch Evolution Within Genomes

45. 45 Phylogeny based on a universal common ancestor Evolution Within Genomes

46. 46 Contribution to the evolution of genomes –Segmental duplication –Genome rearrangement –Loss of gene function HGT leads to mixing of genes among organisms Evolution Within Genomes

47. 47 Inferred by comparing genes in different species Why a mouse develops into a mouse and not a human –Genes are expressed at different times –In different tissues –In different amounts –In different combinations –Example: cystic fibrosis gene Gene Function and Expression Patterns

48. 48 Gene Patterns Chimp DNA: 98.7% identical to human Chimp protein genes: 99.2% identical Experiment: human and chimp brain cells –Patterns of gene transcription activity differed –Same genes transcribed Patterns and levels of transcription varied Posttranscriptional differences

49. 49 Gene Expression Speech –FOXP2 gene: single point mutation = impaired speech and grammar but not language comprehension –FOXP2 found in chimps, gorillas, orangutans, rhesus macaques, and mice –FOXP2 protein in mice and humans differs by only 3 AA, 2 AA in other primates Gene expressed in areas of brain that affect motor function

50. 50 The difference of only 2 AA sequences for FOXP2 appears to have made it possible for language to arise –Selective pressure for the 2 FOXP2 mutations –Allow brain, larynx and mouth to coordinate to produce speech –Linked to signaling and gene expression –FOXP2 mutation in mice-no squeak ! Gene Expression

51. 51 Gene Pattern and Expression Diverse life forms emerge from similar toolkits of genes To understand functional difference: –Look at time and place of expression Small changes in a protein can affect gene function

52. 52 Nonprotein-coding DNA Repetitive DNA 30% of animal; 40-80% of plant genomes Mice & human repetitive DNA similar –Retrotransposon DNA in both species: independently ended up in comparable regions –May not be “junk” DNA –A single retrotransposon mutation can cause heritable differences in coat color in mice

53. 53 Genome Size and Gene Number Genome size has varied over evolutionary time Increases or decreases in size do not correlate with number of genes Polyploidy in plants does not by itself explain differences in genome size A greater amount of DNA is explained by the presence of introns and nonprotein- coding sequences than gene duplicates

54. 54 Disease Sequences conserved between humans and pufferfish provide clues for understanding the genetic basis of human disease Amino acids: –Critical to protein function are preserved –Changes more likely to cause disease Pufferfish genome  conserved sequences in humans

55. 55 Closely related organisms enhance medical research –Use mouse and rat genome to compare to human –Use mice and rats to detect disease from genetic mutations Aid medical research in developing treatments for human diseases Disease

56. 56 Pathogen-host genome differences reveal drug targets –Malaria: Human disease caused by a protist with the mosquito as a vector –~ 2.5 million deaths/year Disease

57. 57 apicoplast –Plasmodium falciparum: 5300 genes Hides in RBCs Subcellular component called apicoplast 12% of protein encoded go to apicoplast Makes fatty acids: target apicoplast and possibly kill the parasite Disease

58. 58 Chagas Disease –Trypanasoma cruzi: insect borne protozoan –Kills ~ 21,000 people/ year with 18 million suffering from infection –Genome sequencing completed in 2005 –Common core of 6200 genes shared among the three pathogens T. cruzi, Leishmania major, T. brucei. Disease

59. 59 Comparative genomics may aid in drug development Disease

60. 60 Crop Improvement Model plant genomes provide links to genetics of crop plants Beneficial bacterial genes can be located and utilized –Pseudomonas fluorescens naturally protects plant roots from disease –Work on identifying chemical pathways –Understanding pathways = more effective methods of crop protection