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

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

Petrov & Hartl (1998) Mol. Biol. Evol. 15:293-302

Estimating the age of ‘pseudogene-like’ retrotransposon insertion alleles

D. mel - D. sim speciation

Bergman & Bensasson (2007) PNAS 104:11340-5

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Retrotransposon demographics in D. melanogaster

Bartolome et al. (2009) Genome Biology 10:R22

Horizontal transfer of D. melanogaster TE families

silent site divergence

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.

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)

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)

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

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Expected allele frequency fits observed allele frequency over a wide range of ages

-8 -7 -6 -5 -4 -3

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log(subs/site)

observed-expected

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

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

Justin Blumenstiel Fiona He

Nicolas SvetecWolfgang Stephan

Acknowledgements