The Darwinian Genome: Genetic and Molecular Evidence for Evolution - PowerPoint PPT Presentation

1 / 194
About This Presentation
Title:

The Darwinian Genome: Genetic and Molecular Evidence for Evolution

Description:

The Darwinian Genome: Genetic and Molecular Evidence for Evolution – PowerPoint PPT presentation

Number of Views:541
Avg rating:3.0/5.0
Slides: 195
Provided by: DAN391
Category:

less

Transcript and Presenter's Notes

Title: The Darwinian Genome: Genetic and Molecular Evidence for Evolution


1
The Darwinian Genome Genetic and Molecular
Evidence for Evolution
  • Dan Graur
  • University of Houston

http//nsm.uh.edu/dgraur/
2
(No Transcript)
3
An introductory true story The Baby Fae Affair
4
On October 26, 1984, Dr. Leonard Bailey placed
the heart of a baboon into the chest of Baby Fae,
an infant born with a severe heart defect. Baby
Fae seemed to do well for a few days then her
body mounted a massive immunological attack on
the foreign tissue and rejected the graft. Baby
Fae's death came as no surprise to scientists
familiar with the evolutionary realities that
preclude cross-species transplants.
5
Before the Baby Fae incident, Bailey spent almost
a decade vainly pursuing research grants. His
work in xenografts, largely unknown and
unreviewed, had not appeared in scientific
journals and was funded by Bailey and his
friends. During the seven years preceding the
Baby Fae baboon transplant, he performed some 160
cross-species transplants, mostly on sheep and
goats, none of whom survived more than 6 months.
6
After the operation, scientists pointed out that
there is no way to match baboon hearts to human
recipients, because baboons have no antigens in
common with human tissue. Bailey maintained that
Baby Fae's death was unrelated to the species of
the organ "donor."
7
In an interview of Bailey by an Australian radio
crew, they queried Bailey on the issue of why he
had chosen a baboon in view of the baboon's
evolutionary distance from humans. Why didnt
you select a chimpanzee heart? Bailey replied,
Er, You see, I don't believe in evolution.
8
Erasmus Darwin, Zoönomia, 1796. Jean-Baptiste
Lamarck, Philosophie Zoologique, 1809. Charles
Darwin, The Origin of Species, 1859. Scopes v.
Tennessee (Monkey Trial), 1925. Epperson v.
Arkansas, 1968. Edwards v. Aguillard (Louisiana),
1987. Kitzmiller v. Dover Area School District
(Pennsylvania), 2005.
9
What is Science? The hypothetico-deductive model
of the scientific method
  • Fact an observation, accepted as true until
    modified or discarded.
  • Hypothesis a tentative statement leading to
    deductions that can be tested.
  • Law a descriptive generalization.
  • Theory a well substantiated explanation (may
    contain facts, laws, inferences, tested
    hypotheses).
  • Prediction A statement derived from a
    hypothesis, a law, or a theory that may be
    falsified through experiment or observation.

10
The Scientific Method The algorithm
  • Consider a problem. Look for previous
    explanations. If unsatisfactory, then go to 2.
  • Form a conjecture (an explanation).
  • Deduce predictions from the explanation If 2 is
    true, what consequences follow?
  • Test Look for observations refuting predictions
    in 3. If you find such observations, return to 2.
    If you dont, return to 3 or 4.

11
(No Transcript)
12
No amount of experimentation can ever prove me
right a single experiment can prove me
wrong. Albert Einstein
Carl Popper
Albert Einstein
13
(No Transcript)
14
Evolution A process of change in a certain
direction. A process of gradual and peaceful
advance. The historical development of a
biological group. A theory that the various types
of animals and plants have their origin in other
preexisting types and that the distinguishable
differences are due to modifications in
successive generations.
15
Evolution A gradual process in which something
changes into a different and usually more complex
or better form. Change in the genetic composition
of a population as a result of natural selection
and resulting in the development of new species.
The historical development of a related group of
organisms
16
Evolution The gradual process by which the
present diversity of plant and animal life arose
from the earliest and most primitive organisms,
which is believed to have been continuing for the
past 3000 million years.
17
Gene pool
The set of all genetic variants existing in a
population is called the gene pool.
18
Evolution A change in the composition of the
gene pool.
19
Possible Changes 1. allele frequencies 2.
genotype frequencies 3. evolution of a novelty
1.
3.
2.
2.
20
1959
21
(No Transcript)
22
Molecules as documents of evolutionary history
  • Q We may ask the question where in the now
    living systems the greatest amount of information
    of their past history has survived and how it can
    be extracted?
  • A Best fit are the macromolecules which carry
    the genetic information.

23
Palimpsest
24
Searching for an objective reconstruction of the
vanished past is surely the most challenging task
in biology. In one sense, everything in
biology has already been published in the form
of DNA sequences of genomes. 1991
Sydney Brenner
25
Components of Evolutionary Biology
  • The Narrative of Evolution (historical
    description)
  • The Driving Forces of Evolution (mechanistic
    explanation)

26
Descriptive Aspects of Evolution Bacteria lost
their introns. Chimpanzees and humans are
descended from a common ancestor that lived 4-6
million years ago. RNA genomes evolve faster
than DNA genomes. The closest living relatives
of whales and dolphins are hippopotamuses.
27
Mechanistic Aspects of Evolution Origin of
genetic variation is mutation. Most nucleotide
substitutions in protein-coding genes are
selectively neutral. The allele for sickle
cell anemia is maintained in human populations at
relatively high frequencies because heterozygotes
have a higher fitness than homozygotes for the
wild type allele. Darwinian natural selection
is rare at the molecular level.
28
Evolutionary Predictions Molecular Evidence
other types of evidence exist (e.g., fossils,
biogeography, ecology, morphology, comparative
anatomy).
29
1. Functional redundancy
  • A certain function may be performed by different
    molecular sequences.
  • The similarity or dissimilarity among proteins or
    DNA sequences should reflect evolutionary
    relationships.

30
1. Functional redundancy
  • Test case cytochrome b (A ubiquitous protein
    found in all eukaryotes. A component of a
    respiratory complex).

31
1. Functional redundancy
Prediction 1 If the evolutionary narrative is
correct, then human cytochrome c should be more
similar to that of chimpanzee than to that of cow.
32
1. Functional redundancy
Testing Number of amino acid differences between
protein sequences Human-Chimp 0
differences Human-Cow 5 Human-Yeast
30 Human-Candida 51
33
Testing Number of nucleotide differences among
DNA sequences
34
2. Genomic redundancy
  • Since the guiding principle in evolution is
    survival, rather than efficiency, genomes may
    contain redundant sequences and junk DNA.

35
1-2 trillion cells
2 ? 23 46 chromosomes
Males 3.2 3.1 6.3 billion nucleotides Females
3.2 3.2 6.4 billion nucleotides
36
The entire complement of genetic material carried
by an individual is called the genome
37
atggcgagagaggtgcctatagagaaattgagaaacataggtatagttgc
tcacattgacgcgggtaaaacta cgactaccgagagaattctctattac
acgggtaagacttacaagataggtgaagttcacgaaggtgctgcaac ga
tggactggatgccccaggaaaaggaaagaggtataaccataaccgttgca
acgaccgcatgttattggacg
agaaacggggagaggtatcaaataaacataattgacacacccggacacgt
tgacttctccgttgaagttgtacgttccatgaaagttctcgacggaatag
ttttcatattctccgcggttgaaggtgtgcaacctcagtccgaagcaaac
tggagatgggcggacaggttccaagttccgaggatagccttcataaacaa
gatggaccgtctgggtgcggatttttacagagtgtttaaggaaatagaag
aaaagctaaccataaagcccgttgccattcaaatacccctgggagcggag
gaccagtttgaaggtgttatagatctaatggaaatgaaggcaataaggtg
gctcgaagaaaccctcggagctaaatacgaagtagtagacattcctccag
aataccaggaaaaggctcaagaatggcgcgaaaagatgatagaaaccatc
gtagaaaccgacgacgagttaatggaaaagtacttagaaggacaggaaat
atctatagatgaactaagaaaagctttaagaaaggcaacaatagagagaa
agctcgttcccgttctttgcggttctgcattcaagaacaaaggtgttcaa
ccccttcttgacgcagttatagattacctgccttctcctatagaccttcc
tcccgttaaggggacaaatcccaagaccggggaagaagaggtcagacacc
cctctgacgacgaacccttctgcgcttacgcctttaaggttatgtccgac
ccgtatgccggacaacttacctacatcagagtgttctcaggaacgctaaa
agcgggttcttacgtctacaacgcaaccaaggacgaaaagcaaagggctg
gaagacttcttctcatgcacgcgaactccagagaggaaatacagcaggtt
tccgcgggtgaaatttgtgcagttgtaggactagacgccgcaacgggtga
tactctctgtgatgaaaagcaccccataatccttgaaaagcttgaattcc
ctgaccccgttatatctatggctatagagccaaagaccaagaaggaccaa
gaaaaactctcacaagttctcaacaagttcatgaaagaggatccaacctt
cagggcaacaaccgatcccgaaactggtcagatactcatacacggaatgg
gtgagctccacctcgaaataatggttgacagaatgaagagggaatacgga
attgaagtgaacgtcggtaaaccgcaggttgcttacaaggaaaccatcag
gaaaaaggcaattggtgagggtaagttcatcaagcaaactggtggtagag
ggcagtacggtcacgcgataatcgaaatcgaacccctccccagaggtgcg
ggatttgaattcatagacgacattcacggaggagttatccccaaagaatt
cataccctccgttgagaagggtgtaaaggaagctatgcaaaacggaattc
tcgcaggataccccgttgttgacgttagagttagactctttgacggttct
taccacgaagttgactcttcggacatagcattccaggttgcgggttcctt
ggcattcaaagatgcagccaaaaaggcagatcccgttcttctggaaccca
taatggaagttgaagtggaaactcccgaaaagtacgtgggtgacgttata
ggtgaccttaactccagaagaggaaagattatgggaatggaaaacaaggg
agttataacagtcataaaggctcacgttcccctcgcagagatgttcggat
acgctacgacgctcaggagcttgacacaaggtaggggaacctttataatg
aaattttcccactacgacgaagttc
Page 1 out of 1,500,000
38
Transcribed
Untranscribed
DNA
Proteins
RNA
39
95-98.5 junk partial evidence
Junk is real!
40
Some genes and even chromosomes are
dispensable.
41
with apologies to Irina Dunn, Australian feminist
(1970).
42
Large amounts of repetitive DNA are present.
50
43
98.5 of the human genome does not code for
proteins. What does it do?
7 types of repeats account for 44 of the genome
44
Recurrence of chromosomal segments
Science 2911304-1351
45
(No Transcript)
46
Large numbers of mobile or ex-mobile elements are
present.
About 42 of the genome is made of mobile or
ex-mobile elements. About 99.99 of all mobile
elements are dead.
47
3. No evidence for anthropocentrism
Does the human genome support the hypothesis that
humans are the pinnacle of creation?
48
Human chromosome 22 48,000,000 bp December 1999
49
(No Transcript)
50
(No Transcript)
51
Measures of genome size
1. Chromosome number 2. DNA length 3. Number of
genes
52
Logarithmic scale 4 orders of magnitude
max
mean
min
53
Human karyotype 46 chromosomes
54
Myrmecia pilosula (males) (1)
Jumping jack
55
Haplopappus gracilis (4)
Yellow spiny daisy
56
Pisum sativum (14)
57
Helianthus annuus (34)
Sunflower
58
Felis catus (38)
59
Homo sapiens (46)
Canis familiaris (78)
60
Tympanoctomys barrerae (102)
Red viscacha rat
61
Senecio roberti-friesii (90)
Robert Friesis groundsel (belongs to the daisy
family)
62
Atlantic Adonis blue
Lysandra atlantica (250)
63
Netted adder's-tongue (a fern)
Ophioglossum reticulatum (1260)
64
K-value paradox Complexity does not correlate
with chromosome number.
Ophioglossum reticulatum
Homo sapiens
Lysandra atlantica
46
250
1260
65
Genome Size
66
largest
Logarithmic scale 7 orders of magnitude
mean
smallest
105
106
107
108
109
1010
1011
1012
DNA length (bp)
67
Mycoplasma genitalium
A parasite of ciliated epithelial cells in
genital and respiratory tracts. The smallest
known genome of any free-living organism.
105
106
107
108
109
1010
1011
1012
DNA length (bp)
68
Plasmodium falciparum
The human malaria parasite.
105
106
107
108
109
1010
1011
1012
DNA length (bp)
69
Tetrodon fluviatilis

Green-spotted pufferfish
105
106
107
108
109
1010
1011
1012
DNA length (bp)
70

Miniopterus schreibersii
Schreiber's long-wing bat
105
106
107
108
109
1010
1011
1012
DNA length (bp)
71
Homo sapiens
105
106
107
108
109
1010
1011
1012
DNA length (bp)
72
Proechimys trinitatis
Trinidad spiny rat

105
106
107
108
109
1010
1011
1012
DNA length (bp)
73
Triturus cristatus

Great crested newt
105
106
107
108
109
1010
1011
1012
DNA length (bp)
74
Ophioglossum petiolatum

Stalked adder's tongue (fern)
105
106
107
108
109
1010
1011
1012
DNA length (bp)
75
Amoeba dubia
105
106
107
108
109
1010
1011
1012
DNA length (bp)
76
(No Transcript)
77
105
106
107
108
109
1010
1011
1012
DNA length (bp)
78
(No Transcript)
79
C-value paradox Complexity does not correlate
with genome size.
80
3.
Number of Genes
81
1998
82
15 February 2001
1st draft
83
2001
84
21 October 2004
finished sequence
85
2005
20,000-25,000 protein-coding genes
86
N-value paradox Complexity does not correlate
with gene number.

25,000 genes
25,000 genes
60,000 genes
87
Information content
lt
6.4 billion letters in a four-letter alphabet
88
4. Lack of originality
  • There is nothing new in evolution.
  • Molecular characters are comparable.
  • It is possible to reconstruct the evolutionary
    relationships between any two organisms.

89
Humans are not at all original in comparison with
other organisms.
90
The differences between the human and chimpanzee
genomes
1 fusion
91
The differences between the human and chimpanzee
genomes
9 inversions
92
The differences between the human and chimpanzee
genomes
The human and chimpanzee genomes differ from each
other by 1.06 fixed single-nucleotide
substitutions.
a few other changes entrances and exits of
virogens and transposable elements, death of
genes, creation of pseudogenes, etc.
93
5. Irreducible compexity does not exists
  • Organs of extreme perfection and complication
    and sudden evolutionary novelties are neither.

94
Darwin on the eye
Reason tells me, that if numerous gradations from
a simple and imperfect eye to one complex and
perfect can be shown to exist, each grade being
useful to its possessor, as is certainly the
case if further, the eye ever varies and the
variations be inherited, as is likewise certainly
the case and if such variations should be useful
to any animal under changing conditions of life,
then the difficulty of believing that a perfect
and complex eye could be formed by natural
selection should not be considered as subversive
of the theory.
To suppose that the eye with all its inimitable
contrivances for adjusting the focus to different
distances, for admitting different amounts of
light, and for the correction of spherical and
chromatic aberration, could have been formed by
natural selection, seems, I freely confess,
absurd in the highest degree
95
Stages in the Evolution of the Eye
  • Photosensitive epithelium
  • Simple eye cup (gastropods)
  • A deeper cup, providing directional information
    (annelids, gastropods)
  • A pinhole eye (mollusks)
  • Refractive lens (gastropods)
  • Flat, pigmented iris surrounding the lens for
    better focusing (fish, squid, gastropods,
    annelids, and crustaceans)

96
Evolution of the Eye Lens Proteins in Organisms
without a Lens
ß?-crystallin was found in Ciona, a urochordate
(which does not have a lens) Shimeid et al.,
2005, Current Biology 15, 1684.
The conservation of the regulatory hierarchy
controlling ß?-crystallin expression between
organisms with and without a lens shows that the
evolutionary origin of the lens was based on
co-option of pre-existing regulatory circuits
controlling the expression of a key structural
gene in a primitive light-sensing system.
97
Origin of an antifreeze glycoprotein gene
98
Origin of an antifreeze glycoprotein gene
The body fluids of most teleosts (ray-finned
fish) freeze at 1.0C to 0.7C. Therefore, most
fish cannot survive the temperatures of the
Antarctic Ocean (1.9C). Freezing resistance in
Antarctic fish is due to the existence in the
blood of a protein that lowers the freezing
temperature by inhibiting the growth of small ice
crystals, which otherwise may break the cell
membranes.
99
Origin of an antifreeze glycoprotein gene
The giant Antarctic toothfish (Dissostichus
mawsoni)
100
(No Transcript)
101
6. The imperfection of evolution the evolution
of imperfection
  • Evolution produces solutions that work, rather
    than best solutions.
  • Since evolution is neither creative nor
    intelligent, evolutionary products are never
    original.
  • Evolution creates imperfect rather than elegant
    solutions.

102
Mosaic (or chimeric) protein a protein encoded
by a gene that contains regions also found in
other genes.
103
myoglobin Sulculus diversicolor, abalone
YEGVSDAPVTMIGGSAAQSSAMQLLDNLLGVTHSPDKQAFLDEISNYMIP
AHKQLL
YEGVWDTPKKFSGGSAGQSSIFQSLDVLLGVKHDV
GKGAFLQEIREYMPPAHKNFL
indoleamine 2,3-dioxygenase Mus musculus
104
Bricolage moleculaire (Molecular tinkering)
Making due with what exists, rather than creating
what doesnt.
François Jacob
105
7. Shared dead genes (unitary pseudogenes)
  • Functionless elements may be shared by closely
    related organisms due to their common hertage
    from a common ancestor.
  • Some pseudogenes may have no functional
    counterpart.
  • Vestigial (functionless) organs may be found.

106
The genome contains a large number of dead
genes (pseudogenes). Pseudogenes outnumber
functional genes.
107
Unitary pseudogenes
108
L-gulono-g-lactone oxidase
L-gulono-g-lactone oxidase
109
(No Transcript)
110
Exon 10
111
gene death ? pseudogene
organ death ? vestigial organ
112
Muscles to move ears
Vestigial organs
113
Nictitating membrane (third eyelid)
114
Body hair Male mammae
115
3rd molar
116
Caudal vertebrae
117
Vermiform appendix
118
8. Genetic nonfunctionalization accelerates
evolution
  • Genetic changes are constrained by function.
  • Natural selection removes deleterious mutations.
  • The evolution of functional genes is slow.
  • A dead gene is no longer constrained by function.
  • Dead genes evolve faster than functional genes.

119
An evolutionary experiment
Spalax ehrenberghi
120
aA-crystallin
121
In Spalax, aA-crystallin lost its functional role
more than 25 million years ago, when the mole rat
became subterranean and presumably lost use of
its eyes.
122
The aA-crystallin of Spalax evolves 20 times
faster than the aA-crystallins in other rodents,
such as rats, mice, hamsters, gerbils and
squirrel.
123
9. Populations are always genetically variable
  • Genetic variation is mostly unimportant.
  • Deleterious alleles are maintained at low
    frequencies in the population because they may
    hide behind the back of good alleles.

124
Genetic Variability
With the exception of monozygotic twins, which
are NEARLY identical genetically every
one of us is genetically different from every
other human who ever lived. 
125
99.9 of all nucleotides are exactly the same in
all people. 3.2 million polymorphic sites were
identified. Only about 18,000 affect protein
sequences.
126
Percentage of human genetic variation within and
between populations.
Owens and King Science (1999) 286 451-453.
An average population from anywhere in the world
contains 85 of all human variation at autosomal
loci and 81 of all human variation in mtDNA
sequences. Differences among populations from the
same continent contribute another 6 of
variation only 9-13 of genetic variation
differentiates populations from different
continents.
127
The hypothesis that human history has been
characterized by genetically homogeneous groups
(races), distinguished by major biological
differences, is not consistent with genetic
evidence. The myth of major genetic differences
across races can be dismissed.
Owens and King Science (1999) 286 451-453.
128
No major genetic differences across races NO
races
129
9. Populations respond evolutionarily to
environmental change
  • Advantageous genetic variation will take over
    populations in response to stress.
  • Variable populations are able to respond to
    stress faster and more efficiently than
    homogeneous populations.
  • Some evolutionary changes can be observed in real
    time.

130
The genome of the wild-type strain of the
peach-potato aphid (Myzus persicae) contains two
genes encoding esterases.
131
Organophosphorous insecticides, such as
malathion, can be hydrolyzed and sequestered by
esterase.
malathion
132
Following exposure to organophosphorous
insecticides, resistant strains of Myzus persicae
were found to contain up to 80 copies of esterase
genes. The increase in the frequency of the
carriers of these duplications has occurred
within the last 50 years, with the introduction
of the selective agent.

133
  • Antibiotic resistance,
  • Herbicide resistance,
  • Drug resistance,
  • Heavy metal resistance,
  • many other evolutionary phenomena

134
(No Transcript)
135
Evidence for Evolution Evolution Observed
Evolution of drug-resistance in HIV
136
10. Reconstructing evolution
  • By using the principle of common descent, it is
    possible to reconstruct ancestral sequences.
  • Such sequences can then be synthesized and tested
    biochemically.
  • Evolutionary changes have been shown to be
    increasingly adaptive.

137
Evolution of lysozymes in ruminants, langurs
hoatzins
138
(No Transcript)
139
(No Transcript)
140
Ruminants (e.g., cows, deer, sheep, giraffes)
141
Colobine monkeys (e.g., langurs)
142
(No Transcript)
143
Hoatzin (pronouced Watson), an enigmatic South
American bird (most probably related to the
cuckoos).
144
(No Transcript)
145
(No Transcript)
146
Foregut lysozyme
Regular lysozyme
  • Operates best in neutral pH.
  • Is easily cleaved by stomach enzymes.
  • Operates best in very acidic environments.
  • Is extremely resistant to enzymatic cleavage.

147
(No Transcript)
148
Convergent amino-acid replacements in lysozymes
from the foregut of cow, langur and hoatzin. The
lengths of the branches are proportional to the
total numbers of amino-acid replacements along
them. Only convergent replacements are shown,
denoted by a one-letter abbreviation of the
resultant amino acid followed by the position
number at which the replacement occurred.
149
Adaptive replacements contribute to a better
performance of lysozyme at low pH and confer
protection against the proteolytic activities in
the stomach.
150
11. Selection is dependent on the environment
The peculiar case of sickle-cell anemia
151
(No Transcript)
152
Glutamic acid
Valine
153
mvhltpeeksavtalwgkvn vdevggealgrllvvypwtq rffesfgd
lstpdavmgnpk vkahgkkvlgafsdglahld nlkgtfatlselhcdk
lhvd penfrllgnvlvcvlahhfg keftppvqaayqkvvagvan ala
hkyh 147aa
154
mvhltpveksavtalwgkvn vdevggealgrllvvypwtq rffesfgd
lstpdavmgnpk vkahgkkvlgafsdglahld nlkgtfatlselhcdk
lhvd penfrllgnvlvcvlahhfg keftppvqaayqkvvagvan ala
hkyh 147aa
155
(No Transcript)
156
(No Transcript)
157
(No Transcript)
158
(No Transcript)
159
(No Transcript)
160
Intuitive Model
normal fitness
somewhat reduced fitness
reduced fitness
161
(No Transcript)
162
In theory, the end result should have been
directional selection a drastic reduction in HS
allele frequency in the population.
163
Worldwide distribution of sickle-cell anemia
164
In practice, the frequency of the HS allele may
reach enormous values in some populations.
47
165
(No Transcript)
166
(No Transcript)
167
An evolutionary experiment Slave trade
168
Ghana frequency 47
Curaçau no malaria HS frequency 22
Surinam endemic malaria HS frequency 44
169
Assuming the Ghana frequency (q 0.47) is the
equilibrium frequency, and assuming the fitness
of the HSHS homozygote is 0 (t 1), then
170
Overdominant selection is inherently inefficient,
even if the two homozygotes are not viable.
RIP
Powderpuff
Chinese Crested
171
Modiano D, Luoni G, Sirima BS, Simpore J, Verra
F, Konate A, Rastrelli E, Olivieri A, Calissano
C, Paganotti GM, D'Urbano L, Sanou I, Sawadogo A,
Modiano G, Coluzzi M. 2001. Haemoglobin C
protects against clinical Plasmodium falciparum
malaria. Nature 414305-308.
172
E to V HS E to K HC
Hemoglobin C
codon position 6!
Glutamic acid
Lysine
173
Alignment preproinsulin
Xenopus MALWMQCLP-LVLVLLFSTPNTEALANQHL Bos
MALWTRLRPLLALLALWPPPPARAFVNQHL
. .. . Xenopus
CGSHLVEALYLVCGDRGFFYYPKIKRDIEQ Bos
CGSHLVEALYLVCGERGFFYTPKARREVEG
Xenopus
AQVNGPQDNELDG-MQFQPQEYQKMKRGIV Bos
PQVG---ALELAGGPGAGGLEGPPQKRGIV
.. Xenopus
EQCCHSTCSLFQLENYCN Bos
EQCCASVCSLYQLENYCN
.
174
(No Transcript)
175
(No Transcript)
176
An final probably true story
Lactose intolerance
  • Hypolactasia (lactase restriction) low lactase
    activity weaning.
  • Normolactasia (lactase persistence) persistent
    lactase activity into adulthood comparable to the
    neonatal period

177
Lactase persistence
  • All infants have high lactase enzyme activity to
    digest the sugar lactose in milk
  • In most humans, activity declines after weaning,
    but in some it persists

LCTP
178
Molecular basis of lactase persistence
  • Lactase level is controlled by a cis-acting
    element
  • Linkage and LD studies show association of
    lactase persistence with the T allele of a T??C
    polymorphism 14 kb upstream of the lactase gene

Enattah et al. 2002. Nature Genet. 30, 233-237
179
  • Genetics long-range cis-acting regulatory element

C/T 13910
G/A 22018
CCCCAGGC
180
The lactase-persistence haplotype
  • The persistence-associated T allele occurs on a
    haplotype (haplotype A) showing Linkage
    Disequilibrium of over gt 1 Mb

181
Distribution of lactase phenotypes
182
How to explain the high prevalence of lactase
persistence and its geographic distribution?
1) "calcium dependence hypothesis
  • Lactase persistence frequency is high among
    Northern European populations. Rickets and
    osteomalacia were potent selective factors under
    conditions of low solar irradiation

2) milk dependence hypothesis
  • lactase persistence frequency is high among all
    nomadic populations of sub-Saharan Africa (Beja
    in Sudan, Tuaregs in Niger, Fulani in Nigeria,
    Tussi in the Congo basin). Pastoralists in arid
    environments maintain balance of water and
    electrolytes through milk supply.

183
How to explain the high prevalence of lactase
persistence and its geographic distribution?
1) "calcium dependence hypothesis
  • Lactase persistence frequency is high among
    Northern European populations. Rickets and
    osteomalacia were potent selective factors under
    conditions of low solar irradiation

2) milk dependence hypothesis
  • lactase persistence frequency is high among all
    nomadic populations of sub-Saharan Africa (Beja
    in Sudan, Tuaregs in Niger, Fulani in Nigeria,
    Tussi in the Congo basin). Pastoralists in arid
    environments maintain balance of water and
    electrolytes through milk supply.

184
William Paley. 1802. Natural Theology, or
Evidences of the Existence and Attributes of the
Deity
185
(No Transcript)
186
William Paley. 1802. Natural Theology, or
Evidences of the Existence and Attributes of the
Deity
trisomy 13
progeria
187
(No Transcript)
188
(No Transcript)
189
(No Transcript)
190
  • Scientific Literacy in the United States
  • 63 know that the Earth revolves around the Sun
  • 34 know that it takes a year for Earth to
    complete one cycle around the Sun
  • 35 oppose Stem Cell Research
  • 1 are able to define stem cell
  • Rate of scientific literacy 17

191
Science is disinterested in either consensus or
majority voting. Rather, it requires specialist
skills. When public, political, and religious
values are allowed to impinge on scientific work,
science suffers.
192
What happens if we allow religion to inflence
science? An historical example.
Giordano Brunos cosmology (1) The Earth
revolves around the sun, (2) Earth rotates around
its axis, (3) Not all stars are equidistant from
a single center of the universe, (4) The universe
is not hierarchical, (5) The universe is made of
the same elements as Earth, (6) Comets are part
of the natural world, rather than ephemeral
creations, divine instruments, or heavenly
messengers.
Giordano Bruno Born 1548 On February 17, 1600,
brought to the Campo de'Fiori in Rome, his tongue
in a specially designed gag, tied to a pole
naked, and burned at the stake. His crime
Unbelieving a particular literal interpretation
of the Bible.
193
  • December 19, 2007
  • HOUSTON The Texas Education Agency has
    recommended allowing the Institute for Creation
    Research to offer online masters degrees in
    science education. The action comes weeks after
    the Texas Education Agencys director of science,
    Christine Castillo Comer, lost her job after
    superiors accused her of displaying bias against
    creationism and failing to be neutral over the
    teaching of evolution.

194
(No Transcript)
Write a Comment
User Comments (0)
About PowerShow.com