Check out the October issue of GENETICS by looking at the highlights or the full table of contents!

ISSUE HIGHLIGHTS

This Month’s Centennial Articles

Fumio Tajima and the origin of modern population genetics, pp. 389–390

Rasmus Nielsen

Associate Editor Rasmus Nielsen introduces Fumio Tajima’s 1983 Classic on coalescence. This was one of the founding papers of modern population genetics and arguably the first paper to truly demonstrate the tremendous power of the coalescent when deriving statistical properties of a sample of DNA sequences.

Pritchard, Stephens, and Donnelly on population structure, pp. 391–393

John Novembre

Associate Editor John Novembre introduces Pritchard, Stephens, and Donnelly’s 2000 Classic, which described one of the most widespread and important frameworks for inference of population structure.

Probing the depths of biological diversity during the second century of GENETICS, pp. 395–400

Linnea Sandell and Sarah P. Otto

The last century saw the birth of genetics as a field, and the journal Genetics has grown alongside this field. We look to the next century of the journal and argue that we will increasingly grapple with the complexity of biological diversity, from the multiple functions of genes, to the various ways that they interact, to the diversity of roles that genes play across the tree of life.

Darwin’s influence on Mendel: evidence from a new translation of Mendel’s paper, pp. 401–405

Daniel J. Fairbanks and Scott Abbott

and

Experiments on plant hybrids by Gregor Mendel, pp. 407–422

Scott Abbott and Daniel J. Fairbanks

Gregor Mendel studied a German translation of Charles Darwin’s Origin of Species while writing his classic paper, Experiments on Plant Hybrids, which is now in its sesquicen- tennial year. Based on the premise that Darwin’s writings may have influenced Mendel, the authors prepared a new Darwinized English translation of Mendel’s paper by searching for words matching Darwin’s phraseology in Mendel’s original German, with particular attention to passages Mendel marked in his personal copy of Origin of Species. They discovered compelling evidence of Darwin’s influence throughout the two concluding sections of Mendel’s paper, especially in one key paragraph, and have also provided their new translation here.

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Commonalities in development of pure breeds and population isolates revealed in the genome of the Sardinian Fonni’s Dog, pp. 737–755

Dayna L. Dreger, Brian W. Davis, Raffaella Cocco, Sara Sechi, Alessandro Di Cerbo, Heidi G. Parker, Michele Polli, Stefano P Marelli, Paola Crepaldi, and Elaine A Ostrander

The Italian island of Sardinia is well-known in studies of human population isolates. It is also home to the Fonni’s Dog, a breed that has not been subjected to intensive artificial selection, but rather has developed alongside the human population, influenced by geographic isolation and unregulated selection. Dreger et al. characterized the Fonni’s Dog relative to 27 other dog breeds from the Mediterranean region and describe how the breed presents an intriguing model exhibiting the unique demographic composition of the people of Sardinia.

Identification of the target of the retrograde response that mediates replicative lifespan extension in Saccharomyces cerevisiae, pp. 659–673

James C. Jiang, Stefan W. Stumpferl, Anurag Tiwari, Qian Qin, Jose F. Rodriguez-Quihones, and S. Michal Jazwinski

Defective mitochondria signal the nucleus to activate a transcriptional program called the retrograde response in Saccharomyces cerevisiae. This compensates for the accumulation of dysfunctional mitochondria, allowing the cells to live longer under metabolic stress. Jiang et al. show this response requires the transcriptional co-activator SAGA or SLIK/SALSA, and the participation of Sir2 histone deacetylase. Out of the 410 retrograde response target genes, PHO84, encoding a plasma membrane phosphate transporter, was both necessary and sufficient for lifespan extension. This result establishes a link between three cellular compartments in determining yeast longevity.

Restructuring of holocentric centromeres during meiosis in the plant Rhynchospora pubera, pp. 555–568

Andre Marques, Veit Schubert, Andreas Houben, and Andrea Pedrosa-Harand

Holocentric chromosomes, characterized by multiple centromere units along each chromatid, have particular centromere adaptations to ensure regular disjunction during meiosis. Marques et al. show that holocentromeres are organized differently in mitosis and meiosis of Rhynchospora pubera. During meiosis I, several clusters of centromere units accumulate along the poleward surface of bivalents. During meiosis II, cluster-holocentromeres are mostly present in the mid-region of each chromatid. A linear holocentromere organization is restored after meiosis during pollen mitosis.

Comparing the statistical fate of paralogous and orthologous sequences, pp. 475–482

Florian Massip, Michael Sheinman, Sophie Schbath, and Peter F. Arndt

Comparison of exonic sequences from a wide range of vertebrate species reveals a puzzling distribution in the lengths of exact sequence matches. Massip et al. develop a simple mathematical model that explains this observation and show that it stems from the high rate of segmental duplication in exonic sequences and is not a consequence of their coding potential. This model provides a better understanding of the statistical properties and evolution of genomic sequences.

Mitochondrial-nuclear interactions mediate sex-specific transcriptional profiles in Drosophila, pp. 613–630

Jim A. Mossman, Jennifer G. Tross, Nan Li, Zhijin Wu, and David M. Rand

Emerging mitochondrial replacement therapies aim to eliminate deleterious mitochondrial DNA (mtDNA) mutations in offspring. This process involves introducing nuclear DNA into an enucleated donor oocyte containing ‘healthy’ mitochondria. Although a promising avenue for effective therapy, the outcomes of this process will partly depend on how well the mtDNA haplotype and nuclear DNA communicate. Using a mitonuclear genotype panel of Drosophila melanogaster, Mossman et al. show that gene expression is sensitive to mitonuclear co-variation (epistasis) in both sexes. Nuclear DNA variation had similar effects in females and males. However, mtDNA variation had a larger effect in females.

Gene and network analysis of common variants reveals novel associations in multiple complex diseases, pp. 783–798

Priyanka Nakka, Benjamin J. Raphael, and Sohini Ramachandran

A major difficulty in identifying genetic variants underlying complex diseases is that affected individuals may possess multiple and different variants in the same gene or pathway. To address this issue, Nakka et al. introduce PEGASUS, a method for combining information from multiple loci within a gene into a single “gene score” that quantifies its statistical association with a trait of interest. PEGASUS produces gene scores with as much as 10 orders of magnitude higher numerical precision than competing methods. The authors use PEGASUS to discover networks of interacting genes associated with Waist-Hip Ratio, Ulcerative Colitis and Attention-Deficit/Hyperactivity Disorder.

Accurate chromosome segregation at first meiotic division requires AGO4, a protein involved in RNA-dependent DNA methylation in Arabidopsis thaliana, pp. 543–553

Cecilia Oliver, Juan Luis Santos, and Monica Pradillo

Oliver et al. report the importance of a protein required for RNA- dependent DNA methylation (RdDM), AGO4, during meiosis. Mutants defective for this protein display alterations in chromatin conformation around centromeric regions, lagging chromosomes at anaphase I, and defects in spindle organization. These results highlight the importance of AGO4 in ensuring accurate chromosome segregation at first meiotic division in Arabidopsis thaliana.

Statistical methods for testing genetic pleiotropy, pp. 483–497

Daniel J. Schaid, Xingwei Tong, Beth Larrabee, Richard B. Kennedy, Gregory A. Poland, and Jason P Sinnwell

Pleiotropy occurs when a single gene influences more than one trait Current multivariate methods to evaluate pleiotropy test the null hypothesis that none of the traits are associated with a genetic variant. But that means the null will be rejected when only a single trait is associated. To address this limitation, Schaid et al. developed rigorous statistical methods for identifying which traits are associated with genetic variants, and how many are associated, while accounting for correlations among the traits.

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