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Chapter 24

Lecture Outline

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Genome EvolutionChapter 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

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• 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 repetitive5

• 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%)

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• 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

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• 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

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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

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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

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M. truncatula Soybean

Genome size:500 Mb

Genome size:1100 Mb

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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

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Nicotiana sylvestris

Diploid Diploid

Nicotiana tabacum

Allpolyploid

Polyploidy

Duplicate gene loss

Nicotiana tabacum

Nicotiana tomentosiformis

SCIENTIFIC THINKING

Hypothesis: Some duplicated genes may be eliminated afterpolyploidy.Prediction: More duplicate genes will be present when anallopolyploid forms than a few generations later.Test: Make a synthetic polyploid from two Nicotiana speciesand look at the chromosomes under a microscope then andafter 3 generations of self-fertilizing offspring.

Result: Over time, N. tomentosiformis chromosomes are lostor shortened.Conclusion: Chromosomes and genes are preferentiallyeliminated following polyploidy.Further Experiments: Why might the chromosomes and genesof one species be preferentially eliminated? How could youtest 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

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• 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

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• 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

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Human Y chromosome5% of human genome consists of segmental duplications

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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

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Orangutan Gorilla Chimpanzee Human

24 chromosomes

Apes

24 chromosomes 24 chromosomes 23 chromosomes

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• 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

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• 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

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• 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

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Noncoding DNA

• Much of the genome is noncoding-DNA (ncDNA)

• 30% of animal and 40–80% of plant genomes

• Conserved noncoding regions (CNCs) evolve more slowly than expected

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• 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

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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

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• 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

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• 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

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• 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

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• 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

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Human

Nonsynonymous changes

Synonymous changes

2/0

0/5

0/2 0/2

0/7

1/20/5

1/131 0/2

Chimp

Gorilla

Orangutan

Mouse

Rhesusmonkey

• Comparative genomics reveals genetic basis for disease

• Genome comparisons between pathogen and host aid drug development.

• Comparative genomics helps conservation biologists

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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

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• 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

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• 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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• 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

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(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 µm 5 µm2 µm

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• 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

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Genetic diversity of mitochondrial genomes

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