Transcript v4_03_founder_mutations

Founder Mutations
Current Issues in Biology, Volume 4
Scientific American
PowerPoint® Lectures
Lectures by Greg Podgorski, Utah State University
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Concept Review
• A founder mutation is a mutation shared by many
individuals because they share a common ancestor.
• Founder mutations associated with disease are often
recessive and spare individuals who carry only one
copy of the mutant gene.
• This makes it possible for the mutation to spread from
the founder to his or her descendants instead of being
eliminated.
• Founder mutations provide a window to human
migrations.
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Founder Mutations
Concept Review
• Mutations arise by random changes to DNA
sequences.
• Genes can be mutated to cause inherited disease in
two general ways:
1) Different individuals may carry different mutations in
the gene associated with the disease.
2) Precisely the same mutation may be seen again and
again in a disease-associated gene.
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Founder Mutations
Concept Review
• A repeatedly observed disease-causing mutation can
occur if
- A hotspot for mutation is mutated independently in
different individuals.
or
- A mutation occurs in one individual, the founder, and is
transmitted to the founder’s descendants.
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Concept Review
• Everyone who carries the founder mutation also
shares nearby sequences of DNA.
• This shared DNA region is a haplotype.
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Founder Mutations
Concept Review
• Over time, haplotypes
become progressively shorter
because of recombination
between homologous
chromosomes.
• Therefore, the length of the
haplotype provides an estimate
of how long ago the founder
mutation occurred.
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Founder Mutations
Concept Review
• Founder mutations are hundreds to thousands of
times more common than typical mutations that cause
disease.
• Founder mutations reach high frequencies through
natural selection because they provide an advantage to
individuals who carry only one copy of the mutated
gene.
• For example, carrying a single copy of the founder
mutation that causes hereditary hemochromatosis
enhances iron absorption, an advantage when diets are
poor in iron.
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Founder Mutations
Concept Review
• The frequency of a founder mutation represents a
balance between two competing forces – the harm
caused by carrying two copies of the mutation weighted
against the benefit provided by carrying one copy of the
mutation.
• This is balancing selection.
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Founder Mutations
Concept Review
PTC Taste Perception and the Out of Africa Hypothesis
• About 75% of people worldwide perceive the chemical
PTC as extremely bitter; the rest cannot taste it at all.
• The inability to taste PTC is due to a founder mutation.
• In African populations, there are seven different forms
of the gene associated with PTC perception.
• Outside of Africa, there is only one major taster and
one nontaster form of the gene.
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Concept Review
• The nontaster mutation is in a very short haplotype,
indicating an ancient origin for this mutation.
• Two conclusions can be drawn:
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Founder Mutations
Concept Review
• The existence of a single nontaster haplotype is
consistent with the tenet of the Out of Africa hypothesis
that ancestors of modern non-African populations
migrated from Africa about 75,000 years ago. These
migrants carried one major taster and one nontaster
form of the gene.
• The single PTC nontaster mutation suggests that
migrants from Africa did not interbreed with local
populations that almost certainly would have carried
their own unique mutations of this gene.
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Concept Review
The Hemochromatosis Founder Mutation as a Window
to European Migrations
• The hemochromatosis founder mutation is found at
highest frequencies in Celtic peoples of northwestern
Europe and at lower frequencies in other regions of
Europe.
• The Celts were a dominant group in central Europe
2,000 years ago but were largely displaced north and
west by the expanding Roman Empire.
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Founder Mutations
Concept Review
• Did the hemochromatosis founder mutation arise in
central Europe before Celtic migrations? Or did it
originate in today’s Celtic lands and spread
southeastward?
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Concept Review
• The large size of the haplotype that contains the
hemochromatosis mutation indicates that it originated
recently: 60 to 70 generations ago, or about A.D. 800.
• Because this was long after the displacement of the
Celts from central Europe, the mutation must have
arisen in northwestern Europe and spread
southeastward through the founder’s descendants.
• Analysis of founder mutations offers insight into where
we came from and how we came to inhabit modern
homelands.
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Testing Your Comprehension
How many copies of a founder mutation are required to
cause disease?
a) 1
b) 2
c) 4
d) 8
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Testing Your Comprehension
How many copies of a founder mutation are required to
cause disease?
b) 2
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Testing Your Comprehension
If two people have the same genetic disease caused by
a mutation other than a founder mutation, they usually
will have
a) exactly the same mutation in the same gene
b) different mutations in the same gene
c) hotspot mutations in different genes
d) markedly different symptoms
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Testing Your Comprehension
If two people have the same genetic disease caused by
a mutation other than a founder mutation, they usually
will have
b) different mutations in the same gene
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Testing Your Comprehension
Over time, haplotypes become
a) shorter
b) longer
c) more harmful
d) less harmful
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Testing Your Comprehension
Over time, haplotypes become
a) shorter
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Testing Your Comprehension
Balancing selection leads to
a) elimination of founder mutations
b) a continual increase in the frequency of founder
mutations
c) a stable frequency of a founder mutation
d) a fluctuating frequency of a founder mutation
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Testing Your Comprehension
Balancing selection leads to
c) a stable frequency of a founder mutation
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Biology and Society
The investigation of founder mutations and other
markers of human origins shows that human
populations are very closely related. If people could be
educated about their close degree of kinship, this would
help prevent conflicts across the world.
Strongly
Agree
A.
B.
C.
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D.
E.
Strongly
Disagree
Founder Mutations
Thinking About Science
The figure shows two sets of DNA sequences obtained
from 8 different people. The A shown in red is a diseasecausing mutation. Letters in the blue-bordered columns
are DNA sequences that may vary, but do not cause the
disease. Which set comes from people carrying a
founder mutation?
a) The top set
b) The bottom set
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Thinking About Science
The figure shows two sets of DNA sequences obtained
from 8 different people. The A shown in red is a diseasecausing mutation. Letters in the blue-bordered columns
are DNA sequences that may vary, but do not cause the
disease. Which set comes from people carrying a
founder mutation?
b) The bottom set
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Founder Mutations
Interpreting Data and Graphs
• DNA sequences of a small part of one gene from a
healthy individual and three individuals with genetic
disease caused by mutations of this gene are shown in
the following table.
Healthy
ACCGTAC
Diseased 1 ACTCTAC
Diseased 2 TCCCTAC
Diseased 3 ACCCTAG
Which mutation is likely to cause this disease?
Is this a founder mutation?
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings