Local and relaxed clocks, the best of both worlds

Time-resolved phylogenetic methods use information about the time of sample collection to estimate the rate of evolution. Originally, the models used to estimate evolutionary rates were quite simple, assuming that all lineages evolve at the same rate, an assumption commonly known as the molecular clock. Richer and more complex models have since been introduced to capture the phenomenon of substitution rate variation among lineages. Two well known model extensions are the local clock, wherein all lineages in a clade share a common substitution rate, and the uncorrelated relaxed clock, wherein the substitution rate on each lineage is independent from other lineages while being constrained to fit some parametric distribution. We introduce a further model extension, called the flexible local clock (FLC), which provides a flexible framework to combine relaxed clock models with local clock models. We evaluate the flexible local clock on simulated and real datasets and show that it provides substantially improved fit to an influenza dataset. An implementation of the model is available for download from https://www.github.com/4ment/flc.

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Local and relaxed clocks, the best of both worlds

10.7287/peerj.preprints.26744v1 ◽

2018 ◽

Author(s):

Mathieu Fourment ◽

Aaron E Darling

Keyword(s):

Substitution Rate ◽

Rate Variation ◽

Sample Collection ◽

Time Resolved ◽

Local Clock ◽

Model Extension ◽

Complex Models ◽

Flexible Framework ◽

Clock Models ◽

Relaxed Clock

Time-resolved phylogenetic methods use information about the time of sample collection to estimate the rate of evolution. Originally, the models used to estimate evolutionary rates were quite simple, assuming that all lineages evolve at the same rate, an assumption commonly known as the molecular clock. Richer and more complex models have since been introduced to capture the phenomenon of substitution rate variation among lineages. Two well known model extensions are the local clock, wherein all lineages in a clade share a common substitution rate, and the uncorrelated relaxed clock, wherein the substitution rate on each lineage is independent from other lineages while being constrained to fit some parametric distribution. We introduce a further model extension, called the flexible local clock (FLC), which provides a flexible framework to combine relaxed clock models with local clock models. We evaluate the flexible local clock on simulated and real datasets and show that it provides substantially improved fit to an influenza dataset. An implementation of the model is available for download from https://www.github.com/4ment/flc.

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Bayesian detection of convergent rate changes of conserved noncoding elements on phylogenetic trees

10.1101/260745 ◽

2018 ◽

Cited By ~ 2

Author(s):

Zhirui Hu ◽

Timothy B. Sackton ◽

Scott V. Edwards ◽

Jun S. Liu

Keyword(s):

Substitution Rate ◽

Phylogenetic Trees ◽

Rate Variation ◽

Strong Indicator ◽

Convergent Rate ◽

Conserved Noncoding Elements ◽

Bayesian Relaxed Clock ◽

Genomic Regions ◽

Clock Models ◽

Better Than

AbstractConservation of DNA sequence over evolutionary time is a strong indicator of function, and gain or loss of sequence conservation can be used to infer changes in function across a phylogeny. Changes in evolutionary rates on particular lineages in a phylogeny can indicate shared functional shifts, and thus can be used to detect genomic correlates of phenotypic convergence. However, existing methods do not allow easy detection of patterns of rate variation, which causes challenges for detecting convergent rate shifts or other complex evolutionary scenarios. Here we introduce PhyloAcc, a new Bayesian method to model substitution rate changes in conserved elements across a phylogeny. The method assumes several categories of substitution rate for each branch on the phylogenetic tree, estimates substitution rates per category, and detects changes of substitution rate as the posterior probability of a category switch. Simulations show that PhyloAcc can detect genomic regions with rate shifts in multiple target species better than previous methods and has a higher accuracy of reconstructing complex patterns of substitution rate changes than prevalent Bayesian relaxed clock models. We demonstrate the utility of PhyloAcc in two classic examples of convergent phenotypes: loss of flight in birds and the transition to marine life in mammals. In each case, our approach reveals numerous examples of conserved non-exonic elements with accelerations specific to the phenotypically convergent lineages. Our method is widely applicable to any set of conserved elements where multiple rate changes are expected on a phylogeny.

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A mixed relaxed clock model

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2015.0132 ◽

2016 ◽

Vol 371 (1699) ◽

pp. 20150132 ◽

Cited By ~ 33

Author(s):

Nicolas Lartillot ◽

Matthew J. Phillips ◽

Fredrik Ronquist

Keyword(s):

Phylogenetic Trees ◽

Multiple Time Scales ◽

Rate Variation ◽

Multiple Time ◽

Short Term ◽

Clock Model ◽

Long Term Trends ◽

Clock Models ◽

Relaxed Clock

Over recent years, several alternative relaxed clock models have been proposed in the context of Bayesian dating. These models fall in two distinct categories: uncorrelated and autocorrelated across branches. The choice between these two classes of relaxed clocks is still an open question. More fundamentally, the true process of rate variation may have both long-term trends and short-term fluctuations, suggesting that more sophisticated clock models unfolding over multiple time scales should ultimately be developed. Here, a mixed relaxed clock model is introduced, which can be mechanistically interpreted as a rate variation process undergoing short-term fluctuations on the top of Brownian long-term trends. Statistically, this mixed clock represents an alternative solution to the problem of choosing between autocorrelated and uncorrelated relaxed clocks, by proposing instead to combine their respective merits. Fitting this model on a dataset of 105 placental mammals, using both node-dating and tip-dating approaches, suggests that the two pure clocks, Brownian and white noise, are rejected in favour of a mixed model with approximately equal contributions for its uncorrelated and autocorrelated components. The tip-dating analysis is particularly sensitive to the choice of the relaxed clock model. In this context, the classical pure Brownian relaxed clock appears to be overly rigid, leading to biases in divergence time estimation. By contrast, the use of a mixed clock leads to more recent and more reasonable estimates for the crown ages of placental orders and superorders. Altogether, the mixed clock introduced here represents a first step towards empirically more adequate models of the patterns of rate variation across phylogenetic trees. This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.

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Viral Substitution Rate Variation Can Arise from the Interplay between Within-Host and Epidemiological Dynamics

The American Naturalist ◽

10.1086/672000 ◽

2013 ◽

Vol 182 (4) ◽

pp. 494-513 ◽

Cited By ~ 14

Author(s):

Stacy O. Scholle ◽

Rolf J. F. Ypma ◽

Alun L. Lloyd ◽

Katia Koelle

Keyword(s):

Substitution Rate ◽

Rate Variation ◽

Substitution Rate Variation

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A delay-deterministic model for inferring fitness effects from time-resolved genome sequence data

10.1101/229963 ◽

2017 ◽

Author(s):

Nuno R. Nené ◽

Alistair S. Dunham ◽

Christopher J. R. Illingworth

Keyword(s):

Finite Population ◽

Deterministic Model ◽

Sequence Data ◽

Evolutionary System ◽

Deterministic Models ◽

Time Resolved ◽

General Application ◽

Fitness Effects ◽

Alternative Approach ◽

Complex Models

ABSTRACTA common challenge arising from the observation of an evolutionary system over time is to infer the magnitude of selection acting upon a specific genetic variant, or variants, within the population. The inference of selection may be confounded by the effects of genetic drift in a system, leading to the development of inference procedures to account for these effects. However, recent work has suggested that deterministic models of evolution may be effective in capturing the effects of selection even under complex models of demography, suggesting the more general application of deterministic approaches to inference. Responding to this literature, we here note a case in which a deterministic model of evolution may give highly misleading inferences, resulting from the non-deterministic properties of mutation in a finite population. We propose an alternative approach which corrects for this error, which we denote the delay-deterministic model. Applying our model to a simple evolutionary system we demonstrate its performance in quantifying the extent of selection acting within that system. We further consider the application of our model to sequence data from an evolutionary experiment. We outline scenarios in which our model may produce improved results for the inference of selection, noting that such situations can be easily identified via the use of a regular deterministic model.

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