Detecting branching rate heterogeneity in multifurcating trees with applications in lineage tracing data.

Understanding cellular birth rate differences is crucial for predicting cancer progression and interpreting tumor-derived genetic data. Lineage tracing experiments enable detailed reconstruction of cellular genealogies, offering new opportunities to measure branching rate heterogeneity. However, the lineage tracing process can introduce complex tree features that complicate this effort.

Elevated HIV Viral Load is Associated with Higher Recombination Rate In Vivo.

HIV's exceptionally high recombination rate drives its intrahost diversification, enabling immune escape and multidrug resistance within people living with HIV. While we know that HIV's recombination rate varies by genomic position, we have little understanding of how recombination varies throughout infection or between individuals as a function of the rate of cellular coinfection. We hypothesize that denser intrahost populations may have higher rates of coinfection and therefore recombination.

Brain tropism acquisition: The spatial dynamics and evolution of a measles virus collective infectious unit that drove lethal subacute sclerosing panencephalitis.

It is increasingly appreciated that pathogens can spread as infectious units constituted by multiple, genetically diverse genomes, also called collective infectious units or genome collectives. However, genetic characterization of the spatial dynamics of collective infectious units in animal hosts is demanding, and it is rarely feasible in humans. Measles virus (MeV), whose spread in lymphatic tissues and airway epithelia relies on collective infectious units, can, in rare cases, cause subacute sclerosing panencephalitis (SSPE), a lethal human brain disease.

Elevated HIV viral load is associated with higher recombination rate .

HIV's exceptionally high recombination rate drives its intra-host diversification, enabling immune escape and multi-drug resistance within people living with HIV. While we know that HIV's recombination rate varies by genomic position, we have little understanding of how recombination varies throughout infection or between individuals as a function of the rate of cellular coinfection. We hypothesize that denser intra-host populations may have higher rates of coinfection and therefore recombination.

State-dependent evolutionary models reveal modes of solid tumour growth.

Spatial properties of tumour growth have profound implications for cancer progression, therapeutic resistance and metastasis. Yet, how spatial position governs tumour cell division remains difficult to evaluate in clinical tumours. Here, we demonstrate that faster division on the tumour periphery leaves characteristic genetic patterns, which become evident when a phylogenetic tree is reconstructed from spatially sampled cells.

Understanding patterns of HIV multi-drug resistance through models of temporal and spatial drug heterogeneity.

Triple-drug therapies have transformed HIV from a fatal condition to a chronic one. These therapies should prevent HIV drug resistance evolution, because one or more drugs suppress any partially resistant viruses. In practice, such therapies drastically reduced, but did not eliminate, resistance evolution.

The clarifying role of time series data in the population genetics of HIV.

HIV can evolve remarkably quickly in response to antiretroviral therapies and the immune system. This evolution stymies treatment effectiveness and prevents the development of an HIV vaccine. Consequently, there has been a great interest in using population genetics to disentangle the forces that govern the HIV adaptive landscape (selection, drift, mutation, and recombination).

Evolutionary Dynamics in Structured Populations Under Strong Population Genetic Forces.

In the long-term neutral equilibrium, high rates of migration between subpopulations result in little population differentiation. However, in the short-term, even very abundant migration may not be enough for subpopulations to equilibrate immediately. In this study, we investigate dynamical patterns of short-term population differentiation in adapting populations via stochastic and analytical modeling through time.

The Relationship Between Haplotype-Based and Haplotype Length.

The population-genetic statistic [Formula: see text] is used widely to describe allele frequency distributions in subdivided populations. The increasing availability of DNA sequence data has recently enabled computations of [Formula: see text] from sequence-based "haplotype loci." At the same time, theoretical work has revealed that [Formula: see text] has a strong dependence on the underlying genetic diversity of a locus from which it is computed, with high diversity constraining values of [Formula: see text] to be low.

Correction: Within-patient mutation frequencies reveal fitness costs of CpG dinucleotides and drastic amino acid changes in HIV.

[This corrects the article DOI: 10.1371/journal.pgen.

Within-patient mutation frequencies reveal fitness costs of CpG dinucleotides and drastic amino acid changes in HIV.

HIV has a high mutation rate, which contributes to its ability to evolve quickly. However, we know little about the fitness costs of individual HIV mutations in vivo, their distribution and the different factors shaping the viral fitness landscape. We calculated the mean frequency of transition mutations at 870 sites of the pol gene in 160 patients, allowing us to determine the cost of these mutations.

A spatio-temporal assessment of simian/human immunodeficiency virus (SHIV) evolution reveals a highly dynamic process within the host.

The process by which drug-resistant HIV-1 arises and spreads spatially within an infected individual is poorly understood. Studies have found variable results relating how HIV-1 in the blood differs from virus sampled in tissues, offering conflicting findings about whether HIV-1 throughout the body is homogeneously distributed. However, most of these studies sample only two compartments and few have data from multiple time points.

More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1.

In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep.

The population genetics of drug resistance evolution in natural populations of viral, bacterial and eukaryotic pathogens.

Drug resistance is a costly consequence of pathogen evolution and a major concern in public health. In this review, we show how population genetics can be used to study the evolution of drug resistance and also how drug resistance evolution is informative as an evolutionary model system. We highlight five examples from diverse organisms with particular focus on: (i) identifying drug resistance loci in the malaria parasite Plasmodium falciparum using the genomic signatures of selective sweeps, (ii) determining the role of epistasis in drug resistance evolution in influenza, (iii) quantifying the role of standing genetic variation in the evolution of drug resistance in HIV, (iv) using drug resistance mutations to study clonal interference dynamics in tuberculosis and (v) analysing the population structure of the core and accessory genome of Staphylococcus aureus to understand the spread of methicillin resistance.

Identifying signatures of selection in genetic time series.

Both genetic drift and natural selection cause the frequencies of alleles in a population to vary over time. Discriminating between these two evolutionary forces, based on a time series of samples from a population, remains an outstanding problem with increasing relevance to modern data sets. Even in the idealized situation when the sampled locus is independent of all other loci, this problem is difficult to solve, especially when the size of the population from which the samples are drawn is unknown.

LDx: estimation of linkage disequilibrium from high-throughput pooled resequencing data.

High-throughput pooled resequencing offers significant potential for whole genome population sequencing. However, its main drawback is the loss of haplotype information. In order to regain some of this information, we present LDx, a computational tool for estimating linkage disequilibrium (LD) from pooled resequencing data.

Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required.