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2 Genome Evolution Chapter 24

Key challenge of modern evolutionary biology is finding a way to link changes in DNA sequences with the evolution of the complex morphological characters used to construct a traditional phylogeny Comparing genomes (entire DNA sequences) of different species provides a powerful new tool for exploring the evolutionary divergence among organisms Genomes are instructions and a history of life 3

4 Schizosaccharomyces pombe (fissionyeast) 13.8 Mb 4,824 genes Saccharomyces cerevisiae (baker’s yeast) 2 µm Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fugu rubripes (puffer fish) 365 Mb 33,609 genes Musmusculus (mouse) Pan troglodytes (chimpanzee) Homo sapiens (human) 3,100Mb 20,000–25,000genes 2,870Mb 22,000genes 2,500Mb 22,698genes Bos taurus (domestic cow) 2,600 Mb 37,000 genes Arabidopsis thaliana (wall cress) Oryza sativa (rice) 125 Mb 25,498 genes Thermoplasma volcanium (archea) 430 Mb 43,000 genes 12.7Mb 5,805genes 23 Mb 5,300 genes Plasmodium falciparum (malariaparasite) Escherichia coli (bacteria) 4.6 Mb 4,377 genes 8,800 × 1.6 Mb 1,478 genes 1 µm 230 Mb 13,749 genes 2500 µm 2,200 Mb 18,500 genes Ornithorynchus anatinus (duck-billed platypus) Anopheles gambiae (mosquito) 97 Mb 20,000 genes Caenorhabditis elegans (a translucent worm) 25 µm Drosophila melanogaster (fruit fly) 120 Mb 21,116 genes Zea mays (maize) 2,500 Mb 59,000 genes (mosquito): © Dr. Dennis Kunkel/Visuals Unlimited; (puffer fish): © Digital Vision/Getty Images RF; (duck-billed platypus): © Nicole Duplaix/National Geographic/Getty Images; (chimpanzee): © Digital Vision RF; (translucent worm): © Leslie Saint-Julien, National Human Genome Research Institute; (fruit fly): © David M. Phillips/Visuals Unlimited; (mouse): © G.K & Vikki Hart/Getty Images RF; (domestic cow): © Ian Murray/Getty Images; (human): © James Stevenson/Photo Researchers, Inc.; (wall cress): © Nigel Cattlin/Visuals Unlimited; (maize): © Royalty-Free/Corbis; (rice): Photo by Gary Kramer, USDA Natural Resources Conservation Service; (fission yeast, baker’s yeast): © Steve Gschmeissner/Photo Researchers, Inc.; (bacteria): © doc-stock/Visuals Unlimited; (archea): © Dr. Harald Huber and Prof. Dr. Reinhard Rachel, University of Regensburg, Regensburg, Germany; (malaria parasite): © T. Brain/Photo Researchers, Inc.

5 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), chimpanzee (Pan troglodytes) and human genomes Comparative Genomics

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 –Human genome 97% repetitive DNA but only 6% of Fugu sequence repetitive 6

Human and mouse genomes –Human has 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%) 7 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Musmusculus (mouse) 2,600 Mb 37,000 genes (mouse): © G.K & Vikki Hart/Getty Images RF

8 Human and chimpanzee genomes –Diverged 4.1 MYA –1.5% difference in insertions and deletions (indels) –53 of human-specific indels lead to loss-of- function changes – may be loss of hair or larger cranium –1.06% of the two genomes have consistent differences in single nucleotides

Genomes evolve at different rates A comparison of the mouse and rat genomes reveals a smaller ratio of nonsynonymous to synonymous changes than that seen between humans and chimps Higher ratio in the primates indicates that fewer nonsynonymous mutations have been removed by natural selection than has occurred in mice and rats Chimps have experienced a higher rate of divergent selection than humans since they last shared a common ancestor 9

Plant, fungal, and animal genomes have unique and shared genes –Compare 2 plant genomes Arabidopsis and Oryza Distant relatives but share 80% of genes –Compare plants with animals and fungi 1/3 of Arabidopsis and Oryza are “plant” genes – not found in fungi or animals Many are similar for basic metabolism, genome replication and repair, protein synthesis 10

Whole-genome duplication Polyploidy can result from –Three or more chromosome sets –Genome duplication in one species Autopolyploids – meiotic error –Hybridization of two different species Allopolyploids – hybridization and duplication of the genomes of two different species 11

12 Allopolyploidy Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nicotiana sylvestrisNicotiana tomentosiformis Diploid (SS)Diploid (TT) Allopolyploid (SSTT) Nicotiana tabacum Genome duplication ST hybrid

13 Two allopolyploid events in the history of wheat Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Triticum searsii Triticum monococcum Diploid: 2n=14 (BB)Diploid: 2n=14 (AA) Chromosome doubling Sterile hybrid: 1n =14 (AB) Chromosome doubling Triticum turgidum Tetraploid: 2n = 28 (AABB) Trticum tauschii Diploid: 2n = 14 (CC) Sterile hybrid: 1n =21 (ABC) Chromosome doubling Triticum aestivum Hexaploid: 2n = 42 (AABBCC)

Two avenues of research into genome alterations following polyploidization 1.Paleopolyploids: studies ancient polyploids to reconstruct history Sequence divergence between homologues Presence or absence of duplicated gene pairs from hybridization 14 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display Time (MYA) genome duplication loss of duplicate genes Average number of gene pairs

2.Synthetic polyploids –Crossing plants most closely related to ancestral species and chemically inducing chromosome doubling –Without doubling the plant will be sterile Commercial bananas are 3n and sterile – seedless – aborted ovules appear as brown dots in center of cross section 15

Polyploidy in plants Occurred numerous times in flowering plants 16 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Inferred polyploidy event (MYA) 225–300 25–40 13–15 3–5 11 1–2 11–14 2.5– –70 Sorghum Saccharum (sugarcane) Zea (maize)Oryza (rice)Triticum (wheat) Hordeum (barley) Lycopersicon (tomato) Solanum (potato) Helianthus (sunflower) Lactuca (lettuce) Glycine (soybean) Medicago truncatula Gossypium (cotton) Arabidopsis thaliana Brassica 150–170

Polyploidy in plants Comparison of soybean, forage legume, and garden pea shows a huge difference in genome size Some genomes increased in size through polyploidization Some decreased in size through loss of genes or whole chromosomes 17 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. M. truncatulaSoybean Genome size: 500 Mb Genome size: 1100 Mb 15 44–58 Polyploidy event (MYA)

Modern tobacco, Nicotiana tabacum –Arose from the hybridization and genome duplication of a cross between Nicotiana sylvestris (female parent) and N. tomentosiformis (male parent) –Studied using synthetic crosses –Loss of chromosomes not even –Different rates of genome replication could explain differential loss 18 Nicotiana sylvestris Diploid Nicotiana tabacum Allpolyploid Polyploidy Duplicate gene loss Nicotiana tabacum Nicotiana tomentosiformis SCIENTIFIC THINKING Hypothesis: Some duplicated genes may be eliminated after polyploidy. Prediction: More duplicate genes will be present when an allopolyploid forms than a few generations later. Test: Make a synthetic polyploid from two Nicotiana species and look at the chromosomes under a microscope then and after 3 generations of self-fertilizing offspring. Result: Over time, N. tomentosiformis chromosomes are lost or shortened. Conclusion: Chromosomes and genes are preferentially eliminated following polyploidy. Further Experiments: Why might the chromosomes and genes of one species be preferentially eliminated? How could you test your explanation?

Transposons jump around following polyploidization –Barbara McClintock (Nobel Prize) Hypothesized that they are controlling elements Respond to genome shock and jump into a new position New phenotypes could emerge –Recent work supports this hypothesis 19

20 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 –Paralogues – two genes within an organism that have arisen from the duplication of a single gene in an ancestor –Orthologues – reflects conservation of a single gene from a common ancestor Evolution within genomes

Gene families grow through gene duplication Fates of duplicate gene: –Losing function through subsequent mutation Fate of most duplicated genes –Gaining a novel function through subsequent mutation –Having total function partitioned into the two duplicates 21

Gene duplication in humans –Most likely to occur in three most gene-rich chromosomes –Least amount of duplication in seven chromosomes with the least genes Certain types of human genes more likely to be duplicated –Growth and development genes, immune system genes, and cell-surface receptors 22

23 Human Y chromosome 5% of human genome consists of segmental duplications Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Interchromosomal duplications Intrachromosomal duplications Not sequenced Heterochromatin that is not expressed

Genome reorganization –Humans have 1 fewer chromosome than chimpanzees, gorillas, and orangutans Fusion of two genes into one gene; chromosome 2 in humans 24 OrangutanGorillaChimpanzeeHominid 24 chromosomes Apes 24 chromosomes 23 chromosomes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Rearrangements can provide evolutionary clues but not always definitive proof of how closely related 2 species are Orthologues shared between humans, mice, and chickens –Fewer chromosomal rearrangements between a pair does not imply a closer relationship –Chromosomal rearrangements in mouse ancestors have occurred at twice the rate seen in humans 25

Conservation of synteny –Preservation over evolutionary time of arrangements of DNA segments in related species –Allows researchers to locate a gene in a different species using information about synteny 26 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Soybean M. truncatula 3 c1 b2c2 K 2 d2

Loss of gene function –Way for genomes to evolve –Olfactory receptor (OR) genes Inactivation best explanation for our reduced sense of smell 60% of human OR genes are pseudogenes –Sequences of DNA that are very similar to functional genes but do not produce a functional product Likely explanation is we rely on other senses so selection pressure against loss of OR genes reduced 27

Rearranged DNA can acquire new functions –Icefish survive in Antarctic waters due to antifreeze protein –9 bp of a gene coding for a digestive enzyme evolved to encode part of an antifreeze protein –Series of errors persisted only because it coincided with massive cooling of Antarctic water –Natural selection worked on the chance mutation 28

Noncoding DNA Much of the genome is noncoding-DNA (ncDNA) Repetitive DNA is often retrotransposon DNA 30% of animal and 40–80% of plant genomes Conserved noncoding regions (CNCs) evolve more slowly than expected 29

30 Genes hitchhike from other species –Also called lateral gene transfer –Can lead to phylogenetic complexity –Contrast to vertical gene transfer (VGT) with genes passed generation to generation Horizontal gene transfer (HGT) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. BacteriaEukaryaArchaea Chloroplasts Mitochondria

Extensive gene swapping among early organisms has caused researchers to reexamine base of the tree of life Early phylogenies based on rRNA sequences indicated early prokaryotes gave rise to Bacteria and Archaea Bacterial and archaeal genes found in same organisms as more microbial genomes are sequenced Base of the tree of life is a web rather than a branch 31

Human genome carries more ancient transposons than other genomes –Drosophila may somehow eliminate unnecessary DNA from their genome 75% faster than humans –Human genome has had minimal transposon activity in the last 50 million years –Mice are continuing to add new transposons 32

Gene Function and Expression Patterns 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 Cystic fibrosis gene defect in human causes devastating lung effects but not in mice –Explained by variations in expression of gene 33

Humans and chimps diverged from a common ancestor only about 4.1 MYA –Chimp DNA is 98.7% identical to human –Comparing only protein encoding genes it is 99.2% identical Differences may be explained by different patterns of gene transcription activity – brain cells 34

Microarrays were used that contained 18,000 human genes –RNA isolated from chimp and human brains –Same genes were transcribed in both –But patterns and levels of transcription varied widely –Much of the difference between human and chimp brains lies in which genes are transcribed, and when and where that transcription occurs 35

Speech is uniquely human –Single point mutation in FOXP2 gene means impaired speech and grammar but not language comprehension –FOXP2 found in chimps, gorillas, orangutans, rhesus macaques, and mice Gene expressed in areas of brain that affect motor function –FOXP2 protein in mice and humans differs by only 3 AA; 2 AA in other primates 36

FOXP2 changes may be linked to signaling and gene expression If FOXP2 mutated in mice, they don’t squeak Role may be in neuromuscular pathway to make sounds 37 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Human Nonsynonymous changes Synonymous changes 2/0 0/5 0/2 0/7 1/2 0/5 1/131 0/2 Chimp Gorilla Orangutan Mouse Rhesus monkey

Comparative genomics reveals genetic basis for disease Genome comparisons between pathogen and host aid drug development. Comparative genomics helps conservation biologists 38 Applying Comparative Genomics

Distantly related genomes offer clues for cause of disease –Amino acids critical to protein function tend to be preserved over the course of evolution, and changes at such sites within genes are more likely to cause disease –Comparing humans to pufferfish allows us to find conserved sequences 39

Closely related organisms enhance medical research –Comparing mouse and human genomes quickly revealed the function of 1000 previously unidentified human genes Effects of these genes can be studied in mice, and the results can be used in potential treatments for human diseases –We have extensive data on rat physiology Use rat genome compared to human genome to link genes and disease 40

41 Pathogen-host genome differences reveal drug targets –Malaria Human disease caused by protist Plasmodium falciparum with the mosquito Anopheles gambiae as a vector ~ 1.7– 2.5 million deaths/year Plasmodium has apicoplast where 12% of all its proteins act to produce fatty acids apicoplast

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43 Chagas Disease –Caused by insect borne protozoan Trypanosoma cruzi –Kills ~ 21,000 people/year in Central and South America –Common core of 6,200 genes shared among the three pathogens T. cruzi, Leishmania major, T. brucei –Considered possible drug targets –Currently no effective vaccines and only a few drugs with limited effectiveness

44 (left): © Eye of Science/Photo Researchers, Inc.; (middle): © LSHTM/Stone/Getty Images; (right): © Dr. Dennis Kunkel/Visuals Unlimited Chagas disease African sleeping sickness Leishmania infection Target for drug development 6200 shared core genes 3 µm5 µm2 µm Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Genome comparisons inform conservation biology –Tasmanian devil facial tumor disease –Giant panda population diversity –Polar bear facing extinction Comparisons of mitochondrial genomes reveal genetic diversity in organisms 45

46 Genetic diversity of mitochondrial genomes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Endangered Extinct Not endangered Gorilla Bushman of Southern Africa Wolf Panda Polar bear Mammoth clade II Whale Mammoth Clade I Brown bear European human Stellar sea lion Bison Tasmanian devil Tasmanian tiger Genetic Diversity Within Species