Inference of the properties of the recombination process from whole bacterial genomes, pp. 253–265
M. Azim Ansari and Xavier Didelot
Bacteria reproduce clonally but occasionally exchange genes via recombination. This article presents a novel statistical method to investigate the properties of the recombination process in bacteria using whole genome sequences. The authors provide an estimate of the extent to which recombination tends to happen between related bacteria. The strength of this bias and accounting for its effects has important implications for the role played by recombination in the diversification of bacterial populations.
Genetics of adverse reactions to haloperidol in a mouse diallel: a drug-placebo experiment and Bayesian causal analysis, pp. 321–347
James J. Crowley, Yunjung Kim, Alan B. Lenarcic, Corey R. Quackenbush, Cordelia J. Barrick, Daniel E. Adkins, Ginger S. Shaw, Darla R. Miller, Fernando Pardo-Manuel de Villena, Patrick F. Sullivan, and William Valdar
Haloperidol is a powerful antipsychotic that causes permanently disfiguring side effects in some people. Susceptibility varies from person-to-person, and prior evidence suggests a genetic basis that, if understood, could improve prediction and better target treatment. Crowley et al. met the experimental and analytic challenges of investigating the genetic basis of a drug response by designing an experiment and statistical modeling procedure to estimate the contribution of genetics, epigenetics and sex on haloperidol response in a mouse model.
The basis for evolution of DNA-binding specificity of the Aft1 transcription factor in yeasts, pp. 149–160
Isabelle R. Gonçalves, Natalia Conde e Silva, Cesar La Torre Garay, Emmanuel Lesuisse, Jean Michel Camadro, and Pierre Louis Blaiseau
This article illuminates the evolution of DNA-binding proteins and the sequences they recognize. The Aft1 transcription factors of Saccharomyces cerevisiae and Kluyveromyces lactis activate transcription of the same group of genes but recognize different DNA-binding sites. The authors show that critical differences in a non-conserved region in the Aft1 DNA-binding domain led to changes in DNA-binding specificity that have major consequences for the regulation of iron homeostasis.
Hitchhiking of deleterious alleles and the cost of adaptation in partially selfing species, pp. 281–293
Matthew Hartfield and Sylvain Glémin
How relative benefits of outcrossing and self-fertilization remains a major open question. One theory is that selfing is disadvantageous because it reduces the efficiency of adaptation, but the effects of selfing over multiple sites has seldom been investigated. Hartfield and Glémin investigate a selective sweep that is linked to deleterious alleles and show that unless mutations are highly recessive, outcrossing offers the largest fitness increases compared to selfing, in contrast to previous theory for single alleles. These predictions have major impacts on the theory of mating system evolution.
Estimation of the Spontaneous mutation rate per nucleotide site in a Drosophila melanogaster full-sib family, pp. 313–320
Peter D. Keightley, Rob W. Ness, Daniel L. Halligan, and Penelope R. Haddrill
These authors estimated the mutation rate in Drosophila by sequencing genomes of a family of flies. They found it to be significantly lower than some previous estimates based on mutation accumulation lines. They show that their data collection and analysis pipeline has a false negative rate approaching zero, so a small proportion of genuine mutations is undetected.
Crossover heterogeneity in the absence of hotspots in Caenorhabditis elegans, pp. 137–148
Taniya Kaur and Matthew V. Rockman
and
Sources and structures of mitotic crossovers that arise when BLM helicase is absent in Drosophila, pp. 107–118
Matthew C. LaFave, Sabrina L. Andersen, Eric P. Stoffregen, Julie K. Holsclaw, Kathryn P. Kohl, Lewis J. Overton, and Jeff Sekelsky
Crossovers are crucial for generating genetic diversity, and their distributions across genomes vary among individuals and species. These two articles report on the crossover landscape in two organisms. Kaur and Rockman examined a region of the Caenorhabditis elegans genome at high resolution and found little of the meiotic crossover rate heterogeneity that produces hotspot-rich crossover landscapes in other model species. In contrast, LaFave et al. demonstrate that meiotic crossovers are non-randomly distributed across the genome in Drosophila. These articles provide novel insights into control of meiotic mitotic recombination.
Inducible protein traps with dominant phenotypes for functional analysis of the Drosophila genome, pp. 91–105
Swetha Singari, Naureen Javeed, Nicholas J. Tardi, Suresh Marada, Jeff C. Carlson, Steven Kirk, Judith M. Thorn, and Kevin A. Edwards
This article describes new tools for analyses of gene and protein function in Drosophila, including mutagenesis, live imaging, and purification of protein complexes. The authors developed a transposon that tags proteins with red fluorescent protein and expresses them in specific tissues. They demonstrated the utility of this method, which they call Hostile takeover (Hto), by isolating 26 Hto insertions that cause an eye phenotype, most of which tag developmental or regulatory proteins.
Regulation of aggression by obesity-linked genes TfAP-2 and Twz through octopamine signaling in Drosophila, pp. 349–362
Michael J. Williams, Philip Goergen, Jayasimman Rajendran, Anica Klockars, Anna Kasagiannis, Robert Fredriksson, and Helgi B. Schiöth
Noradrenaline is a central regulator of aggression in mammals, including humans, and its analogue in Drosophila— octopamine—regulates aggression and mating behavior. Williams et al. found that the transcription factor TfAP-2 and its interacting partner Twz are sufficient to effect octopamine signaling, which in turn modulates aggression through the regulation of the satiation hormone Dsk. These results offer a mechanism for how obesity-linked genes modulate behavior by regulating a neuropeptide via monoaminergic signaling.
This Month in the American Journal of Human Genetics
Rare variant extensions of the transmission disequilibrium test: application to autism exome sequence data, Am. J. Hum. Gent. 94(1)
Zongxiao He, Brian J. O’Roak, Joshua D. Smith, Gao Wang, Stanley Hooker, Regie Lyn P. Santos-Cortez, Biao Li, Mengyuan Kan, Nik Krumm, Deborah A. Nickerson, Jay Shendure, Evan E. Eichler, and Suzanne M. Leal
Family based studies avoid the problem of population substructure that is common in population based studies. A common test for association in family based studies is the transmission disequilibrium test. However, this test was not designed for rare variants and as more studies move the NGS sequencing, these methods will be important. In this work, He et al. incorporate methods for identifying rare variants, Combined Multivariate and Collapsing, Weighted Sum Statistic, Burden of Rare Variants and the Variable Threshold, into the transmission disequilibrium framework. When applied to autism spectrum disorder (ASD) trios from the Simons Simplex collection, rare variants in ABCA7, were associated with ASD.