Jessica Lau
Daniel Considine
Ivan O’Shea
Population and Chromosome Genetics
Adaptive introgression between Anopheles
sibling species eliminates a major genomic island
but not reproductive isolation (Clarkson et al,
2014).
Principles taken from the lectures:
Linkage disequilibrium discussed in the lectures is the main principle present in this paper.
Genomic islands of divergence are hypothesized to arise via selection acting on a small
number of physically linked variants, and grow through hitchhiking of additional physically
linked adaptive and neutral loci. Therefore, the arrival of genomic islands is a key violation
of the Hardy Weinberg principle, thus there will be a clear deviation from the expected
Hardy Weinberg allele frequencies for the future generations. Also, other key themes in this
paper include selection and divergence. Recent anthropogenic selection in the A. gambiae
populations has caused adaptive introgression of a major genomic island region, which is
believed to be involved in divergent selection between the S and M forms of A. gambiae.
Alternative hypotheses:
In this paper the examination of evidence of how introgression of such a large, highly
divergent fragment could spread so rapidly and without apparent impact on reproductive
isolation could be explained by three hypotheses:
1. Only part of the 2L Island introgressed, without key loci involved in reproductive
isolation
2. The 2L island is selectively unimportant as speciation is advanced and divergence is
genome wide
3. The divergence of the 2L island results from processes reducing nucleotide diversity
in low recombination regions rather than contemporary divergent selection.
Data collection:
The data collection involved sequencing whole genomes of fifteen wild caught Ghanaian A.
gambiae, from three different subgroups: S homozygous for the Vgsc-1014F kdr mutation,
wild-type M that lack kdr (M-wt) and M homozygous for the kdr allele that introgressed
from S (M-kdr). Furthermore, the mapping of M & S larval form collections from southern
Ghanaian found that overall both forms were in similar frequencies relative to each other.
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Jessica Lau
Daniel Considine
Ivan O’Shea
Population and Chromosome Genetics
Data interpretation:
Manhattan plots show FST based pairwise divergence between groupings of A. gambiae (Mwt, m-kdr, S forms). The plots show the 2L large genomic island region is involved in the
adaptive introgression evolutionary processes. This is also the area where the kdr locus for
insecticide resistance is located. Noting from the graph, all groupings of A. gambiae are
identical in the genome besides the large genomic island of divergence. Due to the
anthropogenic selection pressures induced on the A. gambiae M forms, adaptive
introgression has replaced this large genomic island on the 2L arm of the chromosomes. It
was thought before that this genomic island may have caused the reproductive isolation
between the M & S forms of A. gambiae, however, with the elimination of this major genomic
island via adaptive introgression, there is still presence of reproductive isolation between
sibling A. gambiae forms. Therefore, the genomic island doesn’t contain any reproductive
genes as expected, because replacement of this island still infers reproductive isolation.
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Jessica Lau
Daniel Considine
Ivan O’Shea
Population and Chromosome Genetics
From Beavis to beak colour: A simulation study to
examine how much QTL mapping can reveal
about the genetic architecture of quantitative
traits (Slate, 2013).
Principles taken from the lectures:
This paper aims to highlight the discrepancies in Quantitative Trait Loci (QTL) studies, and
how their application and analysis must be altered when using samples of differing size and
population type. It encompasses principles such as linkage disequilibrium and heritability,
and also underlines some of the key issues that arise with genome-wide association studies,
particularly those carried out on wild outbred populations with a sample size of less than
1,000 individuals. Linkage is fundamental to these types of GWAS studies, as it relies on the
association between predefined markers, known as SNPs, and nearby alleles, particularly
those which may have a measurable phenotypic effect. In this sense, a particular SNP marker
can be associated with a certain haplotype. The paper also addresses the idea of “missing
heritability”. Heritability estimates identify the proportion of phenotypic variance caused by
genetic variation. However, for most traits, this genetic variation is difficult to identify in
QTL studies (Shields, 2011). One of the fundamental problems that biologists have
encountered is how to determine if a few rare alleles of large effect or many common alleles
of small effect are responsible for quantitative traits such as height. This paper gives insight
into how geneticists can develop their analysis approach to better identify causal
alleles.
Alternative Hypotheses:
The hypothesis of this paper is that phenotypic variance of beak colour in Zebra Finches
follows a polygenic model as opposed to the oligogenic model proposed by Schielzeth et al.
2012 (SKEF). SKEF proposed that there were relatively few QTL of large effect that
influenced beak colour. They identified 4 suggestive loci (suggestive loci achieving a test
statistic expected once by chance per genome scan) and none at the significant level (a test
statistic expected with only 5% probability in each genome scan). Slate proposed that this
inflated QTL effect size was an artefact of the Beavis effect and also the result of using an
oligogenic model to interpret the results.
Data Collection:
The data set used in this article was identical to that used by SKEF, using an outbred wild
population of Zebra Finches with a sample size of 1,064 individuals. A panel of 1,396 SNP
markers was used spanning 92% of the genome. A two-step variance components linkage
mapping methodology was used. The first step of this involved the construction of Identityby-descent matrices at lengths of 1 cM evenly spaced throughout the genome. The second
step sees these IBD matrices fitted to a mixed model framework. Likelihood ratio tests are
then used to examine each genomic location and whether it significantly explains the
phenotypic variance.
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Jessica Lau
Daniel Considine
Ivan O’Shea
Population and Chromosome Genetics
Data Interpretation:
One of the major findings from this paper was a strong negative correlation between sample
size and estimated QTL effect size. This overestimation of QTL effect size is known as the
Beavis effect. Most QTL studies assume a sample size of >500 is appropriate to negate the
Beavis effect, but Slate highlights how this may be fundamentally incorrect given than Beavis
worked on QTL studies of inbred populations as opposed to outbred wild populations such
as those in this paper. The paper also found that when the data was fitted to a minor effect
QTL model and extrapolated across all chromosomes, they found empirical results similar to
that of SKEF. This suggests that beak colour follows a more polygenic basis with many QTLs
of small effect, but crucially there may also be rare variants of larger effect also at play.
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