bio 101 chapter 24
DESCRIPTION
Review Presentation Lecture Notes for Chapter 24TRANSCRIPT
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Chapter 24
Lecture Outline
1
2
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
3
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), 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%)
6
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
7
• 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
8
• 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
9
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
10
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
11
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
M. truncatula Soybean
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
12
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
13
14
• 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
15
• 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
16
17
Human Y chromosome5% 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
18
Orangutan Gorilla Chimpanzee Human
24 chromosomes
Apes
24 chromosomes 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
19
• 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
20
• 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
21
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
22
• 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
23
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
24
• 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
25
• 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
26
• 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
27
• 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
28
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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
29
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
30
• 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
31
32
• 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
33
• 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
34
(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
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
35
36
Genetic diversity of mitochondrial genomes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Endangered
ExtinctNot endangered
100
90
80
70
60
50
40
30
20
10
0
Go
rilla
Bu
shm
an o
f S
ou
ther
n A
fric
a
Wo
lf
Pan
da
Po
lar
bea
r
Mam
mo
thcl
ade
II
Wh
ale
Mam
mo
thC
lad
e I
Bro
wn
bea
r
Eu
rop
ean
hu
man
Ste
llar
sea
lion
Bis
on
Tas
man
ian
dev
il
Tas
man
ian
tig
er
Ge
ne
tic
Div
ers
ity
Wit
hin
Sp
ec
ies
92
85
67
77
4344
2825 25
20 1915
10
5