An age-of-allele test of neutrality for transposable element insertions not at equilibrium

An age-of-allele test of neutrality for transposable element insertions not at equilibrium

Justin P. Blumenstiel, Miaomiao He, Casey M. Bergman
(Submitted on 16 Sep 2012)

How natural selection acts to limit the proliferation of transposable elements (TEs) in genomes has been of interest to evolutionary biologists for many years. To describe TE dynamics in populations, many previous studies have relied on the assumption of equilibrium between transposition and selection. However, since TE invasions are known to happen in bursts through time, this assumption may not be reasonable. Here we derive a test of neutrality for TE insertions that does not rely on the assumption of transpositional equilibrium. We consider the case of TE insertions that have been ascertained from a single haploid reference genome sequence and have had their allele frequency estimated in a population sample. By conditioning on age information provided within the sequence of a TE insertion in the form of the number of substitutions that have occurred within the fragment since insertion into a reference genome, we derive the probability distribution for the TE allele frequency in a population sample under neutrality. Taking models of population fluctuation into account, we then test the fit of predictions of our model to allele frequency data from 190 retrotransposon insertion loci in North American and African populations of Drosophila melanogaster. Using this non-equilibrium model, we are able to explain about 80% of the variance in TE insertion allele frequencies. Controlling for nonequilibrium dynamics of transposition and host demography, we demonstrate how one may detect negative selection acting against most TEs as well as evidence for a small subset of TEs being driven to high frequency by positive selection. Our work establishes a new framework for the analysis of the evolutionary forces governing large insertion mutations like TEs or gene duplications.

Our paper: Lineage-specific transposons drove massive gene expression recruitments during the evolution of pregnancy in mammals

Our next “our paper” guest post is by Vincent Lynch [@VinJLynch] who’s just joined the UChicago faculty from a postdoc at Yale. He’s posting about his recently arXived paper:

Lineage-specific transposons drove massive gene expression recruitments during the evolution of pregnancy in mammals. ArXived here.
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Explaining how morphology evolves is a major challenge in biology. While it’s clear that changes in gene regulation are ultimately responsible for the development and evolution of complex characters, we are only just beginning to understand the molecular mechanisms of gene regulatory evolution. This is largely due to the emergence of new technologies, such as mRNA-Seq and ChIP-Seq, which give biologists the tools to explore evolution across the genome and in non-model species.

We took advantage of these methods to explore the evolution of gene expression in the uterus during the origin of pregnancy in mammals. Using mRNA-Seq, we show that gene expression evolved extremely rapidly during major stages in the evolution of pregnancy, for example during the origin of maternal resource provisioning in the stem-lineage of Mammalia, placentation in the stem-lineage of Theria, and implantation in the stem-lineage of Eutheria. Using ChIP-Seq to identify the cis-regulatory elements of genes recruited into uterine expression in mammals suggests that the majority of enhancers and promoters derived from mammalian lineage-specific transposons.

While recent technological advances are changing the way we do biology (see Wagner 2013), as these emerging methods come into the mainstream we must collectively define our new standards of evidence. What experiments and methods build a convincing case for X? Is it sufficient, for example, to conclude that a transposon donated a novel promoter to a gene if a ChIP-Seq peak for a histone mark associated with promoters lies within the transposon? If we then expand that observation across the genome, can we reasonably conclude that transposons are casually responsible for gene regulatory change? For these reasons we chose to post our manuscript as a work-in-progress to arXiv, both as our contribution to the larger discussion of what constitutes the standards of evidence in this emerging field of biology and as an opportunity to receive feedback from our colleagues to complement formal peer-review.

Vincent Lynch

Lineage-specific transposons drove massive gene expression recruitments during the evolution of pregnancy in mammals

Lineage-specific transposons drove massive gene expression recruitments during the evolution of pregnancy in mammals
Vincent J. Lynch, Mauris Nnamani, Kathryn J. Brayer, Deena Emera, Joel O. Wertheim, Sergei L. Kosakovsky Pond, Frank Grützner, Stefan Bauersachs, Alexander Graf, Aurélie Kapusta, Cédric Feschotte, Günter P. Wagner
(Submitted on 22 Aug 2012)

A major challenge in biology is explaining how novel characters originate, however, the molecular mechanisms that underlie the emergence of evolutionary innovations are unclear. Here we show that while gene expression in the uterus evolves at a slow and relatively constant rate, it has been punctuated by periods of rapid change associated with the recruitment of thousands of genes into uterine expression during the evolution of pregnancy in mammals. We found that numerous genes and signaling pathways essential for the establishment of pregnancy and maternal-fetal communication evolved uterine expression in mammals. Remarkably the majority of genes recruited into endometrial expression have cis-regulatory elements derived from lineage-specific transposons, suggesting that that bursts of transposition facilitate adaptation and speciation through genomic and regulatory reorganization.