justin blumenstiel (1) fiona he (2) casey m....
TRANSCRIPT
![Page 1: Justin Blumenstiel (1) Fiona He (2) Casey M. …bergmanlab.genetics.uga.edu/wp-content/uploads/2010/02/...Justin Blumenstiel (1) Fiona He (2) Casey M. Bergman (2) (1) Dept. of Ecology](https://reader033.vdocument.in/reader033/viewer/2022060403/5f0eb35e7e708231d44082af/html5/thumbnails/1.jpg)
Justin Blumenstiel (1)Fiona He (2)
Casey M. Bergman (2)
(1) Dept. of Ecology & Evolutionary Biology, University of Kansas(2) Faculty of Life Sciences, University of Manchester
An age-of-allele test of neutrality for transposable element insertions
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A brief introduction to models of TE evolution
• Selfish DNA sequences, intra-genomic parasites
• Transposition rates >> excision rates
• Equilibrium maintained by transposition-selection balance
• Mechanism of negative selection is debated
• TE insertions at low frequency because of negative selection
• Recent genomic evidence casts doubt on the assumption of equilibrium and inference of negative selection
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Petrov & Hartl (1998) Mol. Biol. Evol. 15:293-302
Estimating the age of ‘pseudogene-like’ retrotransposon insertion alleles
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D. mel - D. sim speciation
Bergman & Bensasson (2007) PNAS 104:11340-5
a_in
vader2
_6
b_m
icro
pia
_4
c_T
abor_
3
d_17.6
_11
e_S
talk
er_
4
f_ro
ver_
3
g_flea_16
h_copia
_28
i_m
dg3_10
j_ro
o_86
k_T
ranspac_4
l_opus_16
m_blo
od_22
n_412_24
o_B
urd
ock_13
p_div
er_
9
q_T
irant_
20
r_jo
ckey2_7
s_H
ele
na_7
t_C
r1a_36
u_baggin
s_6
v_G
4_10
w_D
oc3_7
x_G
5_8
y_B
S_15
z_Juan_9
zz_D
oc_53
0.00
0.02
0.04
0.06
0.08
0.10
0.12D
iverg
ence (
sub/s
ite)
0
1.80
3.60
5.41
7.21
9.01
10.81
Age (
Mya)
Retrotransposon demographics in D. melanogaster
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Bartolome et al. (2009) Genome Biology 10:R22
Horizontal transfer of D. melanogaster TE families
silent site divergence
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Project aims
• Develop a non-equilibrium model of neutral TE evolution that relaxes the assumption of a constant TE insertion rate.
• Obtain allele frequency data for a large sample of TEs in ancestral and derived populations of D. melanogaster.
• Test whether observed TE allele frequencies are consistent with ages of TE insertion estimated from genomic data to infer forces controlling TE evolution.
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An age-of-allele model for TE insertions
• Question: what is the probability that an allele of age t is present in i copies in a sample of n chromosomes?
• Calculate probability of i descendants from a single ancestor given j ancestors (Feller 1957)
• Calculate probability of j ancestors at time t under standard neutral model (Tavare 1984)
• Calculate probability of insertion at time t given s substitutions in a fragment of length l under Poisson process (Bayes 1763)
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Allele frequency data for TE insertions
• 190 loci (90 LTR and 100 non-LTR)
• 2 PCR per loci per strain (TE+flank / L+R flanking regions)
• 12 strains from 2 populations - Zimbabwe (from Stephan Lab) & North Carolina (from Mackay Lab)
• Insertion in genomic sequence is included as 13th allele to account for ascertainment bias
• Individual strain allele frequency data consistent with pooled strain allele frequency data from Gonzalez et al. (2008)
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lower frequencythan expected
higher frequencythan expected
Fit of expected allele frequency under neutral model to observed frequency in North Carolina
0 50 100 150
-50
510
rank difference
observed-expected
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Expected allele frequency fits observed allele frequency over a wide range of ages
-8 -7 -6 -5 -4 -3
-50
510
log(subs/site)
observed-expected
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Preliminary observations
• Majority of TE insertions in North Carolina are at or close to expected frequency given age since insertion under neutrality
• Some loci deviate strongly from predicted frequency and may reflect loci under positive and negative selection
• Model accurately predicts observed allele frequency over wide range of insertion ages
• Model parameterized with current estimate of African population size leads to poor predictions but yields better fit with ancestral population size
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Ongoing and Future Work
• Use model to generate maximum likelihood estimate of Ne under assumption that insertion alleles are neutral
• Analysis of the fit of model to data according to:
- TE class
- TE family
- X vs. autosome
- recombination
• Resolution of best summary statistic(s) to assess global fit of the model to the data
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Justin Blumenstiel Fiona He
Nicolas SvetecWolfgang Stephan
Acknowledgements