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Pollock, D.

Publications and source records attributed to Pollock, D..

2 recordsLinked to original sources

Markov katana: a novel method for Bayesian resampling of parameter space applied to phylogenetic trees

Phylogenetic inference requires a means to search phylogenetic tree space. This is usually achieved using progressive algorithms that propose and test small alterations in the current tree topology and branch lengths. Current programs search tree topology space using branch-swapping algorithms, but proposals do not discriminate well between swaps likely to succeed or fail. When applied to datasets with many taxa, the huge number of possible topologies slows these programs dramatically. To overcome this, we developed a statistical approach for proposal generation in Bayesian analysis, and evaluated its applicability for the problem of searching phylogenetic tree space. The general idea of the approach, which we call Markov katana, is to make proposals based on a heuristic algorithm using bootstrapped subsets of the data. Such proposals induce an unintended sampling distribution that must be determined and removed to generate posterior estimates, but the cost of this extra step can in principle be small compared to the added value of more efficient parameter exploration in Markov chain Monte Carlo analyses. Our prototype application uses the simple neighbor-joining distance heuristic on data subsets to propose new reasonably likely phylogenetic trees (including topologies and branch lengths). The evolutionary model used to generate distances in our prototype was far simpler than the more complex model used to evaluate the likelihood of phylogenies based on the full dataset. This prototype implementation indicates that the Markov katana approach could be easily incorporated into existing phylogenetic search programs and may prove a useful alternative in conjunction with existing methods. The general features of this statistical approach may also prove useful in disciplines other than phylogenetics. We demonstrate that this method can be used to efficiently estimate a Bayesian posterior.

evolutionary biology

Strong and Fluctuating Sequence Constraints Drive Alu Evolution

Though Alu elements are the most common and well-studied transposable elements in the primate genome, Alu evolutionary dynamics remain poorly understood. To better understand these dynamics, we improved our recently introduced Bayesian transposable element ancestral reconstruction method to incorporate automated alignment and be more computationally efficient. We then used it to reconstruct the relationships among almost 800,000 Alu elements in the human genome. We identified the phylogenetic network relating 154 ancestral replicative Alu sequences, and found that the aligned ancestors vary at only 56 out of ~300 sites. We show that the limited number of variable sites among replicative Alu ancestors is best explained by strong sequence constraints on Alu replicative capacity. Moreover, the pattern of variation suggests that sequence constraints fluctuated over the course of Alu evolution, driving the extinction of older Alu subfamilies and the birth of newer ones. Previous analyses have taken the tight clustering of Alu sequences with age as evidence that all Alu sequences are descended from a small number of \"master elements.\" Our results imply instead that the clustering of Alu sequences with age results from fluctuating sequence constraints, and that there were over 4,000 replicative loci during the course of Alu evolution, most of which were disabled by mutation before mutating to new replicative sequences. We also predict which sites have been functionally important for replication, and how these sites have changed over time. The newly clarified dynamics of Alu evolution invalidate assumptions used in common method of transposable element classification and phylogenetics.\n\nSignificance StatementTransposable elements are genomic sequences that can insert copies of themselves elsewhere in the genome. Alu is the most abundant transposable element in primates, making up 10% of the human genome. Due to its ubiquity and tendency to cause genomic instability, Alu has played a major role in shaping primate genomes. Characterizing the trajectory of Alu evolution is important for understanding how the human genome evolved.\n\nPrevious analyses of Alu concluded that a tiny number of elements generated all copies, and existing classifications of Alu reflect that conclusion. In a whole-genome analysis, we determine that many more elements were replicative than previously understood, indicating that current classifications of Alu are flawed. We develop an alternative reconstruction of Alu evolutionary history.

genomics