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Mutation is the ultimate source of all genetic variation and is, therefore, central to evolutionary change. Previous work on Paramecium tetraurelia found an unusually low germline base-substitution mutation rate in this ciliate. Here, we tested the generality of this result among ciliates using Tetrahymena thermophila. We sequenced the genomes of 10 lines of T. thermophila that had each undergone approximately 1,000 generations of mutation accumulation (MA). We applied an existing mutation-calling pipeline and developed a new probabilistic mutation detection approach that directly models the design of an MA experiment and accommodates the noise introduced by mismapped reads. Our probabilistic mutation-calling ...

Contributors
Long, Hongan, Winter, David, Chang, Allan Y.-C., et al.
Created Date
2016-09-15

Influenza virus inflicts a heavy death toll annually and resistance to existing antiviral drugs has generated interest in the development of agents with novel mechanisms of action. Favipiravir is an antiviral drug that acts by increasing the genome-wide mutation rate of influenza A virus (IAV). Potential synergistic benefits of combining oseltamivir and favipiravir have been demonstrated in animal models of influenza, but the population-level effects of combining the drugs are unknown. In order to elucidate the underlying evolutionary processes at play, we performed genome-wide sequencing of IAV experimental populations subjected to serial passaging in vitro under a combined protocol of ...

Contributors
Ormond, Louise, Liu, Ping, Matuszewski, Sebastian, et al.
Created Date
2017-07-19

The most common evolutionary events at the molecular level are single-base substitutions, as well as insertions and deletions (indels) of short DNA segments. A large body of research has been devoted to develop probabilistic substitution models and to infer their parameters using likelihood and Bayesian approaches. In contrast, relatively little has been done to model indel dynamics, probably due to the difficulty in writing explicit likelihood functions. Here, we contribute to the effort of modeling indel dynamics by presenting SpartaABC, an approximate Bayesian computation (ABC) approach to infer indel parameters from sequence data (either aligned or unaligned). SpartaABC circumvents the ...

Contributors
Levy Karin, Eli, Shkedy, Dafna, Ashkenazy, Haim, et al.
Created Date
2017-05-01

In this study, we present a novel methodology to infer indel parameters from multiple sequence alignments (MSAs) based on simulations. Our algorithm searches for the set of evolutionary parameters describing indel dynamics which best fits a given input MSA. In each step of the search, we use parametric bootstraps and the Mahalanobis distance to estimate how well a proposed set of parameters fits input data. Using simulations, we demonstrate that our methodology can accurately infer the indel parameters for a large variety of plausible settings. Moreover, using our methodology, we show that indel parameters substantially vary between three genomic data ...

Contributors
Levy Karin, Eli, Rabin, Avigayel, Ashkenazy, Haim, et al.
Created Date
2015-11-03

Levels of nucleotide diversity vary greatly across the genomes of most species owing to multiple factors. These include variation in the underlying mutation rates, as well as the effects of both direct and linked selection. Fundamental to interpreting the relative importance of these forces is the common observation of a strong positive correlation between nucleotide diversity and recombination rate. While indeed observed in humans, the interpretation of this pattern has been difficult in the absence of high-quality polymorphism data and recombination maps in closely related species. Here, we characterize genetic features driving nucleotide diversity in Western chimpanzees using a recently ...

Contributors
Pfeifer, Susanne, Jensen, Jeffrey, College of Liberal Arts and Sciences, et al.
Created Date
2016-09-27

In species with highly heteromorphic sex chromosomes, the degradation of one of the sex chromosomes will result in unequal gene expression between the sexes (e.g. between XX females and XY males) and between the sex chromosomes and the autosomes. Dosage compensation is a process whereby genes on the sex chromosomes achieve equal gene expression. We compared genome-wide levels of transcription between males and females, and between the X chromosome and the autosomes in the green anole, Anolis carolinensis. We present evidence for dosage compensation between the sexes, and between the sex chromosomes and the autosomes. When dividing the X chromosome ...

Contributors
Rupp, Shawn, Webster, Timothy, Olney, Kimberly, et al.
Created Date
2016-11-09

Eusocial insects, mostly Hymenoptera, have evolved unique colonial lifestyles that rely on the perception of social context mainly through pheromones, and chemoreceptors are hypothesized to have played important adaptive roles in the evolution of sociality. However, because chemoreceptor repertoires have been characterized in few social insects and their solitary relatives, a comprehensive examination of this hypothesis has not been possible. Here, we annotate ∼3,000 odorant and gustatory receptors in recently sequenced Hymenoptera genomes and systematically compare >4,000 chemoreceptors from 13 hymenopterans, representing one solitary lineage (wasps) and three independently evolved eusocial lineages (ants and two bees). We observe a strong ...

Contributors
Zhou, Xiaofan, Rokas, Antonis, Berger, Shelley L., et al.
Created Date
2015-08-12

Male mutation bias, when more mutations are passed on via the male germline than via the female germline, is observed across mammals. One common way to infer the magnitude of male mutation bias, α, is to compare levels of neutral sequence divergence between genomic regions that spend different amounts of time in the male and female germline. For great apes, including human, we show that estimates of divergence are reduced in putatively unconstrained regions near genes relative to unconstrained regions far from genes. Divergence increases with increasing distance from genes on both the X chromosome and autosomes, but increases faster ...

Contributors
Narang, Pooja, Wilson Sayres, Melissa, College of Liberal Arts and Sciences, et al.
Created Date
2016-11-09