Download Founder Effects, Inbreeding and Hybrid Zones Lecture Outline

16-11-21
Lecture Outline
Founder Effects, Inbreeding
and Hybrid Zones
1)  The Amish, Cheetahs
2)  Inbreeding and Identity by Descent
3)  Allele Frequency Clines and the Formation of
Hybrid Zones
4)  Mini Revision Session
Lecture Outline
1)  The Amish, Cheetahs
Lets recall…
•  Genetic Bottlenecks
2)  Inbreeding and Identity by Descent
3)  Allele Frequency Clines and the Formation of
Hybrid Zones
4)  Mini Revision Session
•  Founder effects
•  Drift
Genetic Drift
Genetic Drift
Genetic drift is stronger in a small population than in a large population
One place that drift can be particularly strong is when a population undergoes a
bottleneck
The effect of random sampling is greater in a small population than
in a large population
The human population has almost certainly gone through several
such bottlenecks on our way out of Africa
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Are there human examples?
•  Remember our Halloween chocolate
demonstration
•  Practical this week will review this concept
•  Yes
•  Particularly within religious institutions or in
isolated locations. Populations do not have to be
small now.. If they were once small.
•  Ashkenazi Jewish population is 11 million people,
but may have descended from only 350 people in
the 1300s. •  Iceland is the location of a large population
genomics study
The Amish
The Amish
There are approximately 12,000 Amish in Lancaster county (Pen.). They
are descended from about 400 founders originating from the Swiss
German border with very little recruitment from other populations. The
few converts are well documented.
•  The Amish are an Anabaptist Christian denomination in the
United States and Ontario, Canada
•  Known for their plain dress and limited use of modern devices
such as cars and electricity
•  Most speak a German dialect known as Pennsylvania Dutch
The Amish
Over the generations the number of descendants of these few founders
has grown and the population has therefore expanded (although more
people leave the community than join).
•  excellent records
•  large family size
•  restricted population highly valuable for
genetic studies
The Genetics of Amish Populations
Alan R Shuldiner M.D. "Only about 200 Amish founders came from
Europe to the United States in the early
1700s," Shuldiner notes. "The Amish
population has grown to 30,000 in the
localized area of Lancaster County. …the
Amish are a closed population with a fixed
gene pool, have very large families, and
essentially complete genealogies dating back
14 generations. It's quite a unique situation to
be able to study a specific group of people
who have particularly good characteristics for
genetic research."
1,225,366 names!
386,130 families!
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The Genetics of Amish Populations
The allele frequencies in the Amish population are atypical of the
communities from which they are descended in Europe because of… 1.  Founder events: the first
400 (or so) founders will
have, by chance, had an
atypical collection of genes
2.  Further drift: the small
population size subsequent
to foundation will have
exaggerated further genetic
drift.
The Genetics of Amish Populations
Six of the founders names are responsible for 3/4 of those seen today and a full
1/4 are called Stoltzfus!
As names are unlikely to
confer a selective advantage,
this change in the frequency
of names is most easily
explained as a random or
stochastic change. (Be
careful: they might be
associated with genes that
confer a selective advantage).
The same change would be predicted for Y chromosomes which are also
transmitted down the paternal line, and a similar change for mitochondrial DNA
which is passed down the maternal line.
The Genetics of Amish Populations
The Genetics of Amish Populations
•  Wilma Bias (John Hopkins University) looked at 30-35 genetic systems giving
evidence about 100-150 loci from one blood sample. The loci range from the
well known blood groups to soluble enzymes.
•  It is important to remember that, by
chance some loci will have larger
changes in allele frequency, some
smaller – although those on the Y
chromosome and mitochondria would
be expected to show greater changes.
•  Like the names, some loci show
dramatic frequency changes since
foundation 15%-25% in the case of
Rh- blood. The Genetics of Amish Populations
Questions
Q1) Why would we expect to see greater
genetic drift on the Y chromosome compared
with other parts of the genome?
A)  Smaller effective
population size
Q2) How can Rh –ve have reached high
frequency when it is selected against?
A)  Drift acts on all loci,
Even those subject to selection
It is particularly important for expectant mothers to know their blood's Rh factor.
Occasionally, a baby will inherit an Rh positive blood type from its father while the
mother has a Rh negative blood type. The baby's life could be in danger if the Rh negative mother's immune system attacks
the baby's Rh positive blood. To prevent this, the mother is injected with anti-RhD
IgG immunoglobulin so that the Rh positive erythrocytes from the baby’s blood in
her system are destroyed before her immune system finds them.
Rh –ve is almost
certainly selected
against
The Genetics of Amish Populations
Ellis-van Creveld syndrome (know colloquially as “Six fingered dwarfism”) is
a recessive trait: genealogical studies show that it is only expressed when an
individual carries two copies of the allele.
Extremely rare in the population at
large, however…
…estimates are that 1/7 of the
present day Amish population carry
the gene.
Perhaps only 1 of the 400 founders carried the allele in the ancestral
population (in a single copy, hence the allele frequency would have been
1/800). The allele may have subsequently drifted to high frequency.
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The Genetics of Amish Populations
This syndrome was described by Ellis and van Creveld in 1940. Very few
cases have been reported in the literature.
A follow up study was carried out by
McKusic et al. in 1964, which focussed on
the Amish population. Almost as many
affected individuals were found in this one
group as had been reported in all the
medical literature up to that time.
McKusic et al. estimated that around 5 in
1000 Amish births resulted in EvC. From
this they estimated the frequency of
heterozygous carriers at around 13%.
The Genetics of Amish Populations
How did they arrive at these numbers?
First, lets remember Hardy-Weinberg Under random mating we expect to see Hardy-Weinberg
genotype frequencies:
p = allele frequency of one allele; q = allele frequency of the other
p2
Under Hardy Weinberg proportions we would expect to see p2
homozygotes of this sort, where p is the allele frequency of
the EvC allele. Thus, p2=0.005 and from this we can estimate
that p≈0.07
Again, assuming Hardy Weinberg proportions we would expect
the genotype frequency of heterozygotes to be gAB=2p(1-p),
which works out at around gAB≈0.13
q2
p2
2p(1-p)
(1-p)2
Be sure of this math – under HWE
p2+2pq+q2
The Genetics of Amish Populations
How did they arrive at these numbers?
Let us call the EvC allele the ‘A’ allele and any non-EvC allele
the ‘B’ allele. We will use the symbol gAA to refer to the
homozygous (affected) genotype frequency. This genotype
frequency was estimated at gAA=0.005 from observed
individuals and historical records
2pq
•  Genotype frequency gAA=0.005
•  gAA=p2=0.005
•  p=√p2=√0.005=0.07
•  We know that p+q=1
•  There for q=1-p=1-0.07=0.93
•  Heterzygotes gAB are 2pq or 2(0.07)(0.93) = 0.1302
Therefore: the proportion of carriers gAB=0.13 (rounded)
The Genetics of Amish Populations
The Genetics of Amish Populations
Brief summary…
Notice that the proportion of carriers (gAB≈0.13) is much
larger than the proportion of affected individuals
(gAA=0.005 ).
Why might we generally expect to see this pattern in
recessive diseases?
•  The Amish are a text-book example of genetic drift.
•  A number of disadvantageous alleles have drifted to high frequency, in
spite of the action of selection against them. This reminds us that genetic
drift affects all loci, not just those that are evolving neutrally.
•  Detailed records combined with a polite culture open to conversation
with scientists means that we can investigate genotype and allele
frequencies for certain conditions that would otherwise be hidden from
view.
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Population Bottlenecks in Nature
•  Last Ice Age ended in the Pleistocene
•  Quaternary Mass Extinction Event
•  Ice Age, Climate, Humans
•  Loss of 40 large mammals and mass reduction in
others
Cheetah Population Genetics
Cheetahs
•  95% homozygous loci
–  domestic cats are 24%
–  Mountain gorillas 78%
–  Inbreed Abyssinian cats 62%
•  Two bottlenecks
–  100 000 BCE when they migrated from North America
to Africa and Eurasia
–  12,000 BCE with the Quaternary Extinction S. Fenton
Dobrynin et al. Genome Biology (2015) 16:277
Cheetah Population Genetics
•  So similar you can graft skin from one cheetah
onto another unrelated cheetah without antirejection drugs.
•  Fixed 5 amino acid changing mutations which
impact sperm production leading to 82% of sperm
with odd morphology reducing breeding success
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On site cheetah genomics research
the cheetah genome relative to other mammal genomes. a SNV rate in mammals. SNV rate for each
nt positions, with repetitive regions not filtered. b SNV density in cheetahs, four other felids and human
windows. Of these, 38,661 fragments had lengths less than the specified window size and thus were
hose fragments are contigs with length less than 500 bp, and thus 46,787 windows of total length 2.337 Gb
NVs in protein-coding genes in felid genomes. d The cheetah genome is composed of 93 % homozygous
red feral domestic cat living in St. Petersburg (top) is compared to Cinnamon, a highly inbred Abyssinian cat
ome sequence [19, 20], middle) and a cheetah (Chewbacca, bottom) as described here. Approximately 15,000
or each species were assessed for SNVs. Regions of high variability (>40 SNVs/100 kbp) are colored red;
100 kbp) are colored green. The first seven chromosome homologues of the genomes of Boris, Cinnamon
comparison. The median lengths of homozygosity stretches in cheetahs (seven individuals), African lions
gers, and the domestic cat are presented in Additional file 1: Figure S7
diffusion approximation
m (AFS) implemented in
he DaDi approximation
quency and the observed
space by computing a
he best of distinctive but
The scenarios were simthe results were used
best fit for each model
ls and methods” for the
t identified the optimal
ISB), a two-dimensional
ncestral population that
Human Induced Bottlenecks
•  60% of fish are
overfishedpopulations,
subdivides into two bottlenecked derivative
showed the best fit based on • low
bootstrap
variance
These
populations
and high maximum likelihood (LL
= −43,to587)
are thought
have(see
“Materials and methods”; Additional
file 1: Figure S12;
reduced
Additional file 2: Table S27), asheterozygosity
illustrated inand
Fig. 3.
The DaDi modeling results implyloss
a of
>100,000-year-old
rare alleles
founder event for cheetahs, perhaps a consequence of
their long Pleistocene migration history from North
America across the Beringian land bridge to Asia,
then south to Africa, punctuated by regular population reduction as well as limiting gene flow through
territory protection. Alternatively, Barnett et al. [35]
have postulated, based on a study of ancient DNA
of Miracinonyx trumani (American cheetahs), that today’s
Inbreeding and Identity by Descent
Genetic drift causes allele frequencies to change over time as a result of
sampling from a finite population. However, genotype frequencies are
expected to remain in Hardy Weinberg proportions every generation.
What can cause a deviation from these proportions is inbreeding: defined as
non-random mating of relatives leading to the increased probability of
identity by descent.
Remember that random mating is an assumption of HWT
The Amish actually avoid cousin matings (and closer), so the population is
actually less inbred that you would expect from a random mating
population.
Lecture Outline
1)  The Amish
2)  Inbreeding and Identity by Descent
3)  Allele Frequency Clines and the Formation of
Hybrid Zones
4)  Mini Revision Session
Inbreeding and Identity by Descent
Global distribution of marriages between couples related as second
cousins or closer
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What UK case of inbreeding is most famous?
Inbreeding and Identity by Descent
Inbreeding and Identity by Descent
The probability of identity by descent due to relatedness between parents
can be measured by the parameter f.
Consider an infinitely large population of selfing diploids. Assume that every
individual in the starting population is a heterozygote.
In simple terms, f is the chance that the two gene copies in a diploid
individual are descended from the same copy in an earlier generation.
The greatest possible amount of
inbreeding occurs in selffertilisation. In this case the two gene copies in
the offspring have a probability
f=1/2 of originating from the same
copy in the parent.
Genotype frequencies change over generations until eventually we would be
left with only homozygotes. Notice that the allele frequencies have not
changed from the initial frequency of p=1/2.
Inbreeding and Identity by Descent
Inbreeding and Identity by Descent
Word of caution: The word inbreeding is a bit “fuzzy”
Some people include genetic drift as a sort of inbreeding, others do not.
Better to contrast genetic drift against consanguinity.
In more complex forms of inbreeding the coefficient f can still be worked out
by looking at pedigrees.
Drift and consanguinity are similar in some ways, and complete opposites in
others!
•  Both occur due to a build up of shared ancestry within a population.
•  Drift occurs as a result of finite population size, whereas consanguinity could
technically occur even in an infinitely large population.
•  Drift results in a change in allele frequencies, but genotype frequencies remain
in HWE. Consanguinity results in a change in genotype frequencies, but does
not alter allele frequencies.
In this example the probability of identity by descent comes out at f=1/8.
These two processes have different implications
for e.g. disease
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Inbreeding and Identity by Descent
Questions?
Break
Bottleneck
Those deleterious recessive alleles that
drift up produce increased incidence of
the disorder. This is then reduced by
selection over subsequent generations.
Consanguinity
The incidence of each disorder is
increased, but selection reduces the
incidence rapidly.
Lecture Outline
1)  The Amish
2)  Inbreeding and Identity by Descent
3)  Allele Frequency Clines and the Formation of
Hybrid Zones
4)  Mini Revision Session
Allele Frequency Clines
Selection in favour of a dominant allele…
Allele Frequency Clines
•  Biston betularia (the Peppered
Moth) exists in melanic and
wild-type phenotypes
•  As the melanic (A) allele is
dominant: both AA and AB
individuals express the black
colouration – hence wAA = wAB
•  Industrial melanism
hypothesis: selection in favour
of the melanic form post
industrial revolution
Allele Frequency Clines
Some evidence to support this: Mark recapture experiments found
that the fitness of the melanic morph is higher in areas where they
are prevalent.
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Allele Frequency Clines
•  The industrial revolution did not lead to
the blackening of all trees. The Delamere
Forest near Manchester and Liverpool is
relatively unaffected but the peppered
moths are predominantly melanic there.
Allele Frequency Clines
•  On the other hand the Gonodontis bidentata
(Scalloped Hazel), which are also melanic
right in the heart of the major industrial
centres, are predominantly non-melanic in
Delamere forest.
•  The difference between the two species
may be explained by their dispersal rates.
HOW?
Lecture Outline
1)  The Amish
2)  Inbreeding and Identity by Descent
3)  Allele Frequency Clines and the Formation of
Hybrid Zones
4)  Mini Revision Session
Hybrid Zones
•  Where divergent allopatric populations meet and
interbreed
•  Patterns of interaction can give us information
about hybrid fitness
–  Strengthening of reproductive barriers
–  Weakening of reproductive barriers
–  Continued formation of hybrid individuals
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Strengthening Reproductive Barriers
•  Reinforcement of barriers occurs when hybrids are
less fit
•  Reproductive barriers should be stronger for
sympatric than allopatric species
Weakening of barriers
•  If hybrids are as fit as their parents there can be
substantial gene flow into the parental populations
•  If gene flow is high enough populations may fuse
into a single species. Continued Formation of Hybrids
Hybrid Zones
•  Hybrids are continually formed but the
populations remain distinct
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Meiotic combinations
Hybrid Zones
•  Fused : Fused
•  Unfused : Unfused
•  Hybrid
?
The existence of this frequency cline can be explained by the reduced fitness of
heterozygotes.
HOW?
Hybrid Zones
Hybrid Zones
Hybrid Zones
Weakening of barriers
•  If hybrids are as fit as their parents there can be
substantial gene flow into the parental populations
•  If gene flow is high enough populations may fuse
into a single species. Gene flow never gets far into the other population due to the
reduced fitness of heterozygotes
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How common are hybrids?
•  10% of animals
•  25-30% of plants
•  Most likely closely related, but not always
Fig. 3. Transgressive segregation
on 17 cranial and mandibular measu
and A. schwartzi collected from
A. schwartzi: ●, specimens collecte
lected from St. Lucia (SL) and the G
and factor loadings are presented i
ponding to seven species of Ar
Addition of individuals collecte
including those morphological
A. schwartzi, to our phylogen
statistical support between A.
the formation of a single clade
topological pattern would be ex
were occurring among these
presence of only three AFLP
Small ribosomal RNA
respect to A. jamaicensis and
D-Loop
ization among these species. H
Cytochrome b
typical of A. schwartzi complica
results because it is distinct f
ND1or A. planirostris and exhibits a
ND6
of Artibeus typical of levels th
the genus (∼6% in cyt-b sequ
ND5
ND2
This distinct mitochondrial ge
ulations of Artibeus distribute
southern Lesser Antilles, the
L-strand
bridization between A. jamaice
ND4
sidering recent documentatio
Fig. 3. Transgressive segregation by
H-strand
combination events in mamma
ND4L
on 17 cranial and mandibular measurem
COII
ND3
recombination
among these sp
COIII
A. schwartzi collected from t
ATPase subunitand
8
tify potential
mitochondrial
A. schwartzi:
●, specimens
collected re
fr
A. from
planirostris,
and/or
A.Grena
sch
lected
St. Lucia (SL)
and the
analyse
andAdditionally,
factor loadings previous
are presented
in Ta
sorting with regard to A. schwa
Fig. 2. Mitochondrial (cyt-b) and nuclear (AFLP) phylogenies of species of
The most parsimonious exp
Artibeus
examined
Fig. 1. Neotropical distributions and admixture among Caribbean species of Artibeus. (Left) A. jamaicensis is restricted to west of the
Andes Mountains
in herein and results of a homoplasy excess test performed
ponding
to seven
species
Artibe
on AFLP
(A) Cyt-b and AFLP phylograms showing species-level variation
our AFLP
data
and of
the
exis
South America. A. planirostris is distributed throughout much of South America east of the Andes Mountains. Both species recently have
comedata.
into primary
contact in the southern Lesser Antilles. Inset shows mtDNA haplotype frequencies at the region of primary contact (St. Lucia: n = 48;
St. Vincent:
n = 126;Clades A–F identify ingroup species-level clusters of the Addition
within
the genus.
of individuals
collected
genome
in southern
Lesserf
Grenadines: n = 48; Grenada: n = 33). (Right) Results of a structure analysis of 218 AFLP fragments reveals admixture between the nuclear genomes of
AFLP dataset. Arrow indicates the change in topology with addition of including
those
morphologically
a
mtDNA
genome
was
present
A. jamaicensis and A. planirostris in southern Lesser Antillean populations. Sampled populations for AFLP analyses included (1) A. jamaicensis: Central America
from the southern Lesser Antilles. (B) Results of a homoplasy A. lineage
schwartzi,
our phylogenet
and Jamaica, (2) A. jamaicensis, A. schwartzi, and A. planirostris: St. Lucia, St. Vincent and the Grenadines, and Carriacou Island, individuals
and (3) A. planirostris:
thattohybridized
in the
excess test of 374 AFLP fragments. The y axis identifies basal nodes for each statistical support between A. jam
Grenada, Venezuela, and Ecuador.
or A. planirostris. This hypoth
species indicated in A, and the x axis represents bootstrap support values of
thenome
formation
a single clade
am
of theofnow-extinct
speci
1,000 iterations. Removal of putative hybrid taxa increased bootstrap supalong principal component 1 (PC1), differing from specimens of
analysis remained high (Fig. 2). Structure analyses of A. jamaitopological
pattern
would
be expe
hybridization
and
its mitochon
port
for A.orjamaicensis (clade F) and A. planirostris (clade E) to 91%
A. schwartzi that were grouped outside either
A. values
jamaicensis
censis, A. planirostris, and A. schwartzi indicated genetic admixture
occurring
among these
gress
into populations
of A.spe
ja
95%,within
respectively
(black dots). Solid lines
indicate 100% bootstrap were
A. planirostris (Fig. 3). The majority of the and
variation
our
throughout Lesser Antillean populations and that two and three
A Complete(ish)
Picture
presence
only three
AFLP ba
Lesser of
Antilles
and Venezuela
support
values for
A. schwartzi
wasclades A and C in all analyses.
populations best fit the data (Fig. 1 and Figs. S2 and S3). sample of A. jamaicensis, A. planirostris, and
respect
to
A.
jamaicensis
and
A.
A principal coordinates analysis of the 218 AFLPs identified interpreted as skull size variation, as indicated by positive and relunclear, the distinct mtDNA gp
We can start to build up a picture of what
specimens of A. schwartzi as a cluster between A. jamaicensis and atively uniform loadings of PC1 (which accounted for 80.49% of the
ization
among these
How
in populations
of species.
A. schwartzi
total variance; Table S4). Principal component
2
accounted
for
A. planirostris (Fig. S4).
evolution
like…
of (Fig.
A. schwartzi
complicates
admixture of the genomes
of two really
extantlooks
species,
A. jamaicensis and typical
lands
1). Previous
(22) a
5.36% of the variation in the sample and was interpreted as shape
distinct from
A. planirostris,
and the morphological
variation
observed
throughplex because
pattern itofismitochondria
Mitochondrial DNA Identifications. We compiled mtDNA identivariation. Shape variation among A. jamaicensis,
A. planirostris,
•  First and foremost
there
is genetic
drift results
planirostrisof
andA.exhibits
a ge
fications of A. jamaicensis, A. planirostris, and A. schwartzi from and A. schwartzi was highly similar. A. schwartzi
out was
Lesser
Antillean
populations of A. schwartzi indicates a hybrid or A.
populations
jamaicensi
larger
than
throughout the Neotropics using the sequence data presented here
A. jamaicensis and A. planirostris with respect
to skull
size 1–3
pro- and Fig. S1)
of levelsadmixt
that
origin
(Figs.
AFLP
dataset id- of Artibeus
•  (23).
ThereOur
maynuclear
also be some
selection
(Fig. S1).typical
Thus, nuclear
and mtDNA-based identifications previously reported or sum- portions. Specimens of A. schwartzi collected from St. Vincent
genus
(∼6% variation
in cyt-b sequenc
acting species-level clades corres- theique
entified seven statistically supported
mtDNA
indicat
Questions?
marized (20, 22, 26, 27). A. jamaicensis
haplotypes were distributed represented the most extreme phenotype in the sample (Fig. 3). We
This distinct mitochondrial genom
west of the Andes Mountains in South America (n = 15), identified sympatric phenotypes of A. jamaicensis and A. schwartzi
•  Gene flow homogenises allele
ulations
of
Artibeus
distributed
a
throughout Central America (n = 22), and throughout the Greater
on two islands in the Grenadines (Carriacou and Union) as well as
frequencies between populations
Larsen et al.
and Lesser Antilles (n = 57). A. planirostris haplotypes were dis- on St. Lucia and St. Vincent (Fig. 3).
southern Lesser Antilles, the reg
tributed east of the Andes Mountains throughout much of eastern
bridization between A. jamaicensi
•  Mutation introduces new
South America (n = 189). A single individual with a lower genetic Relaxed Molecular Clock Analyses. Divergence times were estimated
sidering recent documentation
distance with respect to Caribbean A. schwartzi (∼3.3% in cyt- using cyt-b sequence data from all known extant species of Artibeus
genetic variation into
events in mammals (
b sequence) was identified in Venezuela (20); however, our anal- (1,140 bp; 12 species) (SI Materials and Methods). Our results inpopulations that may have lostcombination
it
dicate that the diversification of Artibeus began during the late
yses show the nuclear genome and cranial phenotype of this inrecombination among these speci
due to drift or selection
dividual are typical of A. planirostris. Caribbean mtDNA haplo- Miocene/early Pliocene ∼5.1 million years ago (Mya) [±1.2 million
tify potential mitochondrial recom
types revealed the area of primary contact among multiple species years]. Time to the most recent common ancestor (TMRCA)
•  There are still many processes
A. planirostris, and/or A. schwar
for the clades containing A. jamaicensis, A. planirostris, and
of Artibeus (Fig. 1). Of 91 specimens screened from Puerto Rico
missing from this picture!
Additionally, previous analyses h
A. schwartzi was estimated at 2.5 Mya (± 0.7 million years). The
(n = 33) and the northern Lesser Antilles (n = 58), A. schwartzi
per Mitochondrial
site per million (cyt-b) and nuclear (AFLP) phylogenies of species of
sorting with regard to A. schwartz
haplotypes were identified in three individuals (20). A. schwartzi mean rate of evolution was 0.019 substitutions
Fig. 2.
and 0.0249),
and herein
the
haplotypes were most common in the southern Lesser Antilles. years (95% highest posterior density: 0.0154
The most parsimonious explan
Artibeus
examined
and results of a homoplasy excess test performed
posterior denA. planirostris haplotypes comprised ∼23% of the Grenada pop- estimated Yule birth rate was 0.230 (95%onhighest
AFLP data. (A) Cyt-b and AFLP phylograms showing species-level variation
our AFLP data and the existen
sity: 0.122 and 0.342). A previous hypothesis regarding the timeulation, and a single A. planirostris haplotype was identified as far
within the genus. Clades A–F identify ingroup species-level clusters of the
genome in southern Lesser An
scale of diversification for Artibeina (Artibeus,
Dermanura, and
north as St. Vincent (22).
AFLP
dataset. slow
Arrow
mtDNA genome was present in a
Koopmania) (26) was rejected based on an
inordinately
rateindicates the change in topology with addition of
individuals per
from
Morphometrics. Cranial and mandibular measurements were used
of evolution for the cyt-b gene (0.009 substitutions
sitethe
persouthern Lesser Antilles. (B) Results of a homoplasy
lineage that hybridized in the Ca
excess test ofwith
374major
AFLP fragments. The y axis identifies basal nodes for each
to examine the morphological variation in A. jamaicensis, A. pla- million years) and phylogeographic incompatibilities
or A. planirostris. This hypothesi
nirostris, and A. schwartzi. Descriptive statistics are presented in paleogeographic events in the Neotropicsspecies
(Fig. 4).indicated in A, and the x axis represents bootstrap support values of
nome of the now-extinct species t
Table S3. The multivariate analysis of variance (MANOVA) test
1,000 iterations. Removal of putative hybrid taxa increased bootstrap suphybridization and its mitochondri
identified statistically supported differences among A. jamaicensis, Discussion
port values for A. jamaicensis (clade F) and A. planirostris (clade E) to 91%
A. planirostris, and A. schwartzi (Wilk’s lambda = 0.06; F[34, 96] =
Our results did not directly support any and
of the95%,
threerespectively
hypotheses (black dots). Solid lines indicate 100% bootstrap
gress into populations of A. jama
8.11; P < 0.01). Phenotypic variation among specimens assigned listed above for the origin of A. schwartzi but are similar to the
Lesser Antilles and Venezuela. A
support values for clades A and C in all analyses.
to A. jamaicensis and A. planirostris showed an area of overlap third hypothesis in that the nuclear genome of A. schwartzi is an
unclear, the distinct mtDNA geno
in populations of A. schwartzi on
2 of 6 | www.pnas.org/cgi/doi/10.1073/pnas.1000133107
al.
admixture ofLarsen
theetgenomes
of two extant species, A. jamaicensis and lands (Fig. 1). Previous (22) and
A. planirostris, and the morphological variation observed throughplex pattern of mitochondrial in
Fig. 1. Neotropical distributions and admixture among Caribbean species of Artibeus. (Left) A. jamaicensis is restricted to west of the Andes Mountains in
South America. A. planirostris is distributed throughout much of South America east of the Andes Mountains. Both species recently have come into primary
contact in the southern Lesser Antilles. Inset shows mtDNA haplotype frequencies at the region of primary contact (St. Lucia: n = 48; St. Vincent: n = 126;
Grenadines: n = 48; Grenada: n = 33). (Right) Results of a structure analysis of 218 AFLP fragments reveals admixture between the nuclear genomes of
A. jamaicensis and A. planirostris in southern Lesser Antillean populations. Sampled populations for AFLP analyses included (1) A. jamaicensis: Central America
and Jamaica, (2) A. jamaicensis, A. schwartzi, and A. planirostris: St. Lucia, St. Vincent and the Grenadines, and Carriacou Island, and (3) A. planirostris:
Grenada, Venezuela, and Ecuador.
analysis remained high (Fig. 2). Structure analyses of A. jamaicensis, A. planirostris, and A. schwartzi indicated genetic admixture
throughout Lesser Antillean populations and that two and three
populations best fit the data (Fig. 1 and Figs. S2 and S3).
A principal coordinates analysis of the 218 AFLPs identified
specimens of A. schwartzi as a cluster between A. jamaicensis and
A. planirostris (Fig. S4).
Mitochondrial DNA Identifications. We compiled mtDNA identifications of A. jamaicensis, A. planirostris, and A. schwartzi from
throughout the Neotropics using the sequence data presented here
and mtDNA-based identifications previously reported or summarized (20, 22, 26, 27). A. jamaicensis haplotypes were distributed
west of the Andes Mountains in South America (n = 15),
throughout Central America (n = 22), and throughout the Greater
and Lesser Antilles (n = 57). A. planirostris haplotypes were distributed east of the Andes Mountains throughout much of eastern
South America (n = 189). A single individual with a lower genetic
distance with respect to Caribbean A. schwartzi (∼3.3% in cytb sequence) was identified in Venezuela (20); however, our analyses show the nuclear genome and cranial phenotype of this individual are typical of A. planirostris. Caribbean mtDNA haplotypes revealed the area of primary contact among multiple species
of Artibeus (Fig. 1). Of 91 specimens screened from Puerto Rico
(n = 33) and the northern Lesser Antilles (n = 58), A. schwartzi
haplotypes were identified in three individuals (20). A. schwartzi
haplotypes were most common in the southern Lesser Antilles.
A. planirostris haplotypes comprised ∼23% of the Grenada population, and a single A. planirostris haplotype was identified as far
north as St. Vincent (22).
Morphometrics. Cranial and mandibular measurements were used
to examine the morphological variation in A. jamaicensis, A. planirostris, and A. schwartzi. Descriptive statistics are presented in
Table S3. The multivariate analysis of variance (MANOVA) test
identified statistically supported differences among A. jamaicensis,
A. planirostris, and A. schwartzi (Wilk’s lambda = 0.06; F[34, 96] =
8.11; P < 0.01). Phenotypic variation among specimens assigned
to A. jamaicensis and A. planirostris showed an area of overlap
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along principal component 1 (PC1), differing from specimens of
A. schwartzi that were grouped outside either A. jamaicensis or
A. planirostris (Fig. 3). The majority of the variation within our
sample of A. jamaicensis, A. planirostris, and A. schwartzi was
interpreted as skull size variation, as indicated by positive and relatively uniform loadings of PC1 (which accounted for 80.49% of the
total variance; Table S4). Principal component 2 accounted for
5.36% of the variation in the sample and was interpreted as shape
variation. Shape variation among A. jamaicensis, A. planirostris,
and A. schwartzi was highly similar. A. schwartzi was larger than
A. jamaicensis and A. planirostris with respect to skull size proportions. Specimens of A. schwartzi collected from St. Vincent
represented the most extreme phenotype in the sample (Fig. 3). We
identified sympatric phenotypes of A. jamaicensis and A. schwartzi
on two islands in the Grenadines (Carriacou and Union) as well as
on St. Lucia and St. Vincent (Fig. 3).
Relaxed Molecular Clock Analyses. Divergence times were estimated
using cyt-b sequence data from all known extant species of Artibeus
(1,140 bp; 12 species) (SI Materials and Methods). Our results indicate that the diversification of Artibeus began during the late
Miocene/early Pliocene ∼5.1 million years ago (Mya) [±1.2 million
years]. Time to the most recent common ancestor (TMRCA)
for the clades containing A. jamaicensis, A. planirostris, and
A. schwartzi was estimated at 2.5 Mya (± 0.7 million years). The
mean rate of evolution was 0.019 substitutions per site per million
years (95% highest posterior density: 0.0154 and 0.0249), and the
estimated Yule birth rate was 0.230 (95% highest posterior density: 0.122 and 0.342). A previous hypothesis regarding the timescale of diversification for Artibeina (Artibeus, Dermanura, and
Koopmania) (26) was rejected based on an inordinately slow rate
of evolution for the cyt-b gene (0.009 substitutions per site per
million years) and phylogeographic incompatibilities with major
paleogeographic events in the Neotropics (Fig. 4).
Discussion
Our results did not directly support any of the three hypotheses
listed above for the origin of A. schwartzi but are similar to the
third hypothesis in that the nuclear genome of A. schwartzi is an
Larsen et al.
12
16-11-21
Lecture Outline
1)  The Amish
2)  Inbreeding and Identity by Descent
3)  Allele Frequency Clines and the Formation of
Mini Revision Session
What is
the probability of identity by descent (f) of
an offspring of full sib parents (parents are brother
and sister with the same mother and father)?
Hybrid Zones
4)  Mini Revision Session
Mini Revision Session
First things first; we need to draw a pedigree of
the offspring of full sib parents.
One thing that confuses people is that the
question does not specify the genotypes of
either the parents or the offspring. Mini Revision Session
1.  We know that one gene copy in the
offspring came from the father, and one
from the mother. The question is; where
did each of these come from in the
grandparental generation?
Remember that we are trying to work out the
probability of identity by descent – in
other words, the probability that the two genes
in the offspring are descended from the same
gene copy in an earlier generation. We do not need to know any genotypes to work
this out! To make this point clear, here the
genes in the grandparents are just dots, rather
than letters.
Mini Revision Session
Mini Revision Session
1.  We know that one gene copy in the
offspring came from the father, and one
from the mother. The question is; where
did each of these come from in the
grandparental generation?
1.  We know that one gene copy in the
offspring came from the father, and one
from the mother. The question is; where
did each of these come from in the
grandparental generation?
2.  Looking just at the paternal side, there is
an equal chance that this gene came from
any of the 4 gene copies in the
grandparents. Thus, we can say that the
probability of each of these events is ¼.
2.  Looking just at the paternal side, there is
an equal chance that this gene came from
any of the 4 gene copies in the
grandparents. Thus, we can say that the
probability of each of these events is ¼.
3.  The same is true of the maternal side. The
probability of this gene descending from
each of the genes in the grandparents is
¼. 13
16-11-21
Mini Revision Session
Mini Revision Session
4.  Combining this knowledge, we can work
out the probability that both offspring
genes are descended from the same copy.
Looking at the first grandparental gene (ie.
the first black dot), we know that the
probability of both the maternal and
paternal genes coming from here is
¼ × ¼ = 1/16.
4.  Combining this knowledge, we can work
out the probability that both offspring
genes are descended from the same copy.
Looking at the first grandparental gene (ie.
the first black dot), we know that the
probability of both the maternal and
paternal genes coming from here is
¼ × ¼ = 1/16.
5.  The same is true of the second
grandparental gene (second black dot). In
fact, this is true of any of the 4
grandparental genes.
Mini Revision Session
6.  In summary; there are 4 ways that the
offspring genes could be descended from
the same gene copy. Each of these has
probability 1/16. Thus, the overall
probability of identity by descent is…
1/16 + 1/16 + 1/16 + 1/16 = 4/16
Mini Revision Session
In
a random mating population, there is a disease
that is encoded by a dominant allele. About 50 out
of 1000 individuals have this disease. Calculate the
genotype frequencies for AA, Aa, and aa.
Or
f = 1/4
p2
q2
2pq
p2
Mini Revision Session
+
gAA + gAa = 50/1000 = 0.05
Remember
must add
to 1
gaa = (1 - 0.05) = 0.95
2
p = 0.95
p ≈ 0.974679
q
gAa = 2p(1-p) ≈ 0.04936
0.05
gAA = (1-p)2 ≈ 0.00064
2p(1-p)
(1-p)2
Further Reading
•  Hardy-Weinberg http://anthro.palomar.edu/
synthetic/synth_2.htm
14