Spatial Population Genetics: Its About Time

Many questions that we have about the history and dynamics of organisms have a geographical component: How many are there, and where do they live? How do they move and interbreed across the landscape? How were they moving a thousand years ago, and where were the ancestors of a particular individual alive today? Answers to these questions can have profound consequences for our understanding of history, ecology, and the evolutionary process. In this review, we discuss how geographic aspects of the distribution, movement, and reproduction of organisms are reflected in their pedigree across space and time. Because the structure of the pedigree is what determines patterns of relatedness in modern genetic variation, our aim is to thus provide intuition for how these processes leave an imprint in genetic data. We also highlight some current methods and gaps in the statistical toolbox of spatial population genetics.

An empirical approach to demographic inference with genomic data

Inference with population genetic data usually treats the population pedigree as a nuisance parameter, the unobserved product of a past history of random mating. However, the history of genetic relationships in a given population is a fixed, unobserved object, and so an alternative approach is to treat this network of relationships as a complex object we wish to learn about, by observing how genomes have been noisily passed down through it. This paper explores this point of view, showing how to translate questions about population genetic data into calculations with a Poisson process of mutations on all ancestral genomes. This method is applied to give a robust interpretation to the $f_4$ statistic used to identify admixture, and to design a new statistic that measures covariances in mean times to most recent common ancestor between two pairs of sequences. The method more generally interprets population genetic statistics in terms of sums of specific functions over ancestral genomes, thereby providing concrete, broadly interpretable interpretations for these statistics. This provides a method for describing demographic history without simplified demographic models. More generally, it brings into focus the population pedigree, which is averaged over in model-based demographic inference.

Stochastic population growth in spatially heterogeneous environments

Classical ecological theory predicts that environmental stochasticity increases extinction risk by reducing the average per-capita growth rate of populations. To understand the interactive effects of environmental stochasticity, spatial heterogeneity, and dispersal on population growth, we study the following model for population abundances in $n$ patches: the conditional law of $X_{t+dt}$ given $X_t=x$ is such that when $dt$ is small the conditional mean of $X_{t+dt}^i-X_t^i$ is approximately $[x^imu_i+sum_j(x^j D_{ji}-x^i D_{ij})]dt$, where $X_t^i$ and $mu_i$ are the abundance and per capita growth rate in the $i$-th patch respectivly, and $D_{ij}$ is the dispersal rate from the $i$-th to the $j$-th patch, and the conditional covariance of $X_{t+dt}^i-X_t^i$ and $X_{t+dt}^j-X_t^j$ is approximately $x^i x^j sigma_{ij}dt$. We show for such a spatially extended population that if $S_t=(X_t^1+...+X_t^n)$ is the total population abundance, then $Y_t=X_t/S_t$, the vector of patch proportions, converges in law to a random vector $Y_infty$ as $ttoinfty$, and the stochastic growth rate $lim_{ttoinfty}t^{-1}log S_t$ equals the space-time average per-capita growth rate $sum_imu_iE[Y_infty^i]$ experienced by the population minus half of the space-time average temporal variation $E[sum_{i,j}sigma_{ij}Y_infty^i Y_infty^j]$ experienced by the population. We derive analytic results for the law of $Y_infty$, find which choice of the dispersal mechanism $D$ produces an optimal stochastic growth rate for a freely dispersing population, and investigate the effect on the stochastic growth rate of constraints on dispersal rates. Our results provide fundamental insights into ideal free movement in the face of uncertainty, the persistence of coupled sink populations, the evolution of dispersal rates, and the single large or several small (SLOSS) debate in conservation biology.

Transcriptional regulation: Effects of promoter proximal pausing on speed, synchrony and reliability

Recent whole genome polymerase binding assays have shown that a large proportion of unexpressed genes have pre-assembled RNA pol II transcription initiation complex stably bound to their promoters. Some such promoter proximally paused genes are regulated at transcription elongation rather than at initiation; it has been proposed that this difference allows these genes to both express faster and achieve more synchronous expression across populations of cells, thus overcoming molecular noise arising from low copy number factors. It has been established experimentally that genes which are regulated at elongation tend to express faster and more synchronously; however, it has not been shown directly whether or not it is the change in the regulated step {em per se} that causes this increase in speed and synchrony. We investigate this question by proposing and analyzing a continuous-time Markov chain model of polymerase complex assembly regulated at one of two steps: initial polymerase association with DNA, or release from a paused, transcribing state. Our analysis demonstrates that, over a wide range of physical parameters, increased speed and synchrony are functional consequences of elongation control. Further, we make new predictions about the effect of elongation regulation on the consistent control of total transcript number between cells, and identify which elements in the transcription induction pathway are most sensitive to molecular noise and thus may be most evolutionarily constrained. Our methods produce symbolic expressions for quantities of interest with reasonable computational effort and can be used to explore the interplay between interaction topology and molecular noise in a broader class of biochemical networks. We provide general-purpose code implementing these methods.

Dynamics of the time to the most recent common ancestor in a large branching population

If we follow an asexually reproducing population through time, then the amount of time that has passed since the most recent common ancestor (MRCA) of all current individuals lived will change as time progresses. The resulting MRCA age process has been studied previously when the population has a constant large size and evolves via the diffusion limit of standard Wright--Fisher dynamics. For any population model, the sample paths of the MRCA age process are made up of periods of linear upward drift with slope +1 punctuated by downward jumps. We build other Markov processes that have such paths from Poisson point processes on $mathbb{R}_{++}timesmathbb{R}_{++}$ with intensity measures of the form $lambdaotimesmu$ where $lambda$ is Lebesgue measure, and $mu$ (the family lifetime measure) is an arbitrary, absolutely continuous measure satisfying $mu((0,infty))=infty$ and $mu((x,infty))<infty$ for all $x>0$. Special cases of this construction describe the time evolution of the MRCA age in $(1+beta)$-stable continuous state branching processes conditioned on nonextinction--a particular case of which, $beta=1$, is Fellers continuous state branching process conditioned on nonextinction. As well as the continuous time process, we also consider the discrete time Markov chain that records the value of the continuous process just before and after its successive jumps. We find transition probabilities for both the continuous and discrete time processes, determine when these processes are transient and recurrent and compute stationary distributions when they exist.