Fast and accurate estimation of the covariance between pairwise maximum likelihood distances
Pairwise evolutionary distances are a model-based summary statistic for a set of molecular sequences. They represent the leaf-to-leaf path lengths of the underlying phylogenetic tree. Estimates of pairwise distances with overlapping paths covary because of shared mutation events. It is desirable to take these covariance structure into account in any process that compares or combines distances to increase precision. In this paper, we present a fast estimator for the covariance of two pairwise maximum likelihood distances, estimated under general Markov models. The estimator is based on a conjecture (going back to Nei and Jin, 1989) which links the covariance to path lengths. We prove it here under a simple symmetric substitution model. In a simulation, we show that our estimator outperforms previously published ones in terms of the mean squared error.