An extended reply to Mendez et al.: The ‘extremely ancient’ chromosome that still isn’t

An extended reply to Mendez et al.: The ‘extremely ancient’ chromosome that still isn’t

Eran Elhaik, Tatiana V. Tatarinova, Anatole A. Klyosov, Dan Graur
(Submitted on 15 Oct 2014)

Earlier this year, we published a scathing critique of a paper by Mendez et al. (2013) in which the claim was made that a Y chromosome was 237,000-581,000 years old. Elhaik et al. (2014) also attacked a popular article in Scientific American by the senior author of Mendez et al. (2013), whose title was “Sex with other human species might have been the secret of Homo sapiens’s [sic] success” (Hammer 2013). Five of the 11 authors of Mendez et al. (2013) have now written a “rebuttal,” and we were allowed to reply.
Unfortunately, our reply was censored for being “too sarcastic and inflamed.” References were removed, meanings were castrated, and a dedication in the Acknowledgments was deleted. Now, that the so-called rebuttal by 45% of the authors of Mendez et al. (2013) has been published together with our vasectomized reply, we decided to make public our entire reply to the so called “rebuttal.” In fact, we go one step further, and publish a version of the reply that has not even been self-censored.
Now, that the so-called rebuttal by 45% of the authors of Mendez et al. (2013) has been published together with our vasectomized reply, we decided to make public our entire reply to the so called “rebuttal.” In fact, we go one step further, and publish a version of the reply that has not even been self-censored.

Massive bursts of transposable element activity in Drosophila

Massive bursts of transposable element activity in Drosophila

Robert Kofler, Viola Nolte, Christian Schlötterer
doi: http://dx.doi.org/10.1101/010231

The evolutionary dynamics of transposable element (TE) insertions have been of continued interest since TE activity has important implications for genome evolution and adaptation. Here, we infer the transposition dynamics of TEs by comparing their abundance in natural D. melanogaster and D. simulans populations. Sequencing pools of more than 550 South African flies to at least 320-fold coverage, we determined the genome wide TE insertion frequencies in both species. We show that 46 (49%) TE families in D. melanogaster and 44 (47%) in D. simulans experienced a recent burst of activity. The bursts of activity affected different TE families in the two species. While in D. melanogaster retrotransposons predominated, DNA transposons showed higher activity levels in D. simulans. We propose that the observed TE dynamics are the outcome of the demographic history of the two species, with habitat expansion triggering a period of rapid evolution.

Association Mapping across Numerous Traits Reveals Patterns of Functional Variation in Maize

Association Mapping across Numerous Traits Reveals Patterns of Functional Variation in Maize

Jason G Wallace, Peter Bradbury, Nengyi Zhang, Yves Gibon, Mark Stitt, Edward Buckler
doi: http://dx.doi.org/10.1101/010207
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ABSTRACT

Phenotypic variation in natural populations results from a combination of genetic effects, environmental effects, and gene-by-environment interactions. Despite the vast amount of genomic data becoming available, many pressing questions remain about the nature of genetic mutations that underlie functional variation. We present the results of combining genome-wide association analysis of 41 different phenotypes in ~5,000 inbred maize lines to analyze patterns of high-resolution genetic association among of 28.9 million single-nucleotide polymorphisms (SNPs) and ~800,000 copy-number variants (CNVs). We show that genic and intergenic regions have opposite patterns of enrichment, minor allele frequencies, and effect sizes, implying tradeoffs among the probability that a given polymorphism will have an effect, the detectable size of that effect, and its frequency in the population. We also find that genes tagged by GWAS are enriched for regulatory functions and are ~50% more likely to have a paralog than expected by chance, indicating that gene regulation and neofunctionalization are strong drivers of phenotypic variation. These results will likely apply to many other organisms, especially ones with large and complex genomes like maize.

RNA-Seq analysis and annotation of a draft blueberry genome assembly identifies candidate genes involved in fruit ripening, biosynthesis of bioactive compounds, and stage-specific alternative splicing

RNA-Seq analysis and annotation of a draft blueberry genome assembly identifies candidate genes involved in fruit ripening, biosynthesis of bioactive compounds, and stage-specific alternative splicing

Vikas Gupta, April Dawn Estrada, Ivory Clabaugh Blakley, Rob Reid, Ketan Patel, Mason D. Meyer, Stig Uggerhoj Andersen, Allan F. Brown, Mary Ann Lila, Ann Loraine
doi: http://dx.doi.org/10.1101/010116

Background: Blueberries are a rich source of antioxidants and other beneficial compounds that can protect against disease. Identifying genes involved in synthesis of bioactive compounds could enable breeding berry varieties with enhanced health benefits. Results: Toward this end, we annotated a draft blueberry genome assembly using RNA-Seq data from five stages of berry fruit development and ripening. Genome-guided assembly of RNA-Seq read alignments combined with output from ab initio gene finders produced around 60,000 gene models, of which more than half were similar to proteins from other species, typically the grape Vitis vinifera. Comparison of gene models to the PlantCyc database of metabolic pathway enzymes identified candidate genes involved in synthesis of bioactive compounds, including bixin, an apocarotenoid with potential disease-fighting properties, and defense-related cyanogenic glycosides, which are toxic. Cyanogenic glycoside (CG) biosynthetic enzymes were highly expressed in green fruit, and a candidate CG detoxification enzyme was up regulated during fruit ripening. Candidate genes for ethylene, anthocyanin, and 400 other biosynthetic pathways were also identified. RNA-Seq expression profiling showed that blueberry growth, maturation, and ripening involve dynamic gene expression changes, including coordinated up and down regulation of metabolic pathway enzymes, cell growth-related genes, and putative transcriptional regulators. Analysis of RNA-seq alignments also identified developmentally regulated alternative splicing, promoter use, and 3′ end formation. Conclusions: We report genome sequence, gene models, functional annotations, and RNA-Seq expression data which provide an important new resource enabling high throughput studies in blueberry. RNA-Seq data are freely available for visualization in Integrated Genome Browser, and analysis code is available from the git repository at http://bitbucket.org/lorainelab/blueberrygenome.

Synonymous and Nonsynonymous Distances Help Untangle Convergent Evolution and Recombination

Synonymous and Nonsynonymous Distances Help Untangle Convergent Evolution and Recombination

Peter B. Chi, Sujay Chattopadhyay, Philippe Lemey, Evgeni V. Sokurenko, Vladimir N. Minin
(Submitted on 6 Oct 2014)

When estimating a phylogeny from a multiple sequence alignment, researchers often assume the absence of recombination. However, if recombination is present, then tree estimation and all downstream analyses will be impacted, because different segments of the sequence alignment support different phylogenies. Similarly, convergent selective pressures at the molecular level can also lead to phylogenetic tree incongruence across the sequence alignment. Current methods for detection of phylogenetic incongruence are not equipped to distinguish between these two different mechanisms and assume that the incongruence is a result of recombination or other horizontal transfer of genetic information. We propose a new recombination detection method that can make this distinction, based on synonymous codon substitution distances. Although some power is lost by discarding the information contained in the nonsynonymous substitutions, our new method has lower false positive probabilities than the original Dss statistic when the phylogenetic incongruence signal is due to convergent evolution. We conclude with three empirical examples, where we analyze: 1) sequences from a transmission network of the human immunodeficiency virus, 2) tlpB gene sequences from a geographically diverse set of 38 Helicobacter pylori strains, and 3) Hepatitis C virus sequences sampled longitudinally from one patient.

Fitting the Balding-Nichols model to forensic databases

Fitting the Balding-Nichols model to forensic databases

Rori Rohlfs, Vitor R.C. Aguiar, Kirk E. Lohmueller, Amanda M. Castro, Alessandro C.S. Ferreira, Vanessa C.O. Almeida, Iuri D. Louro, Rasmus Nielsen
doi: http://dx.doi.org/10.1101/009969
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ABSTRACT

Large forensic databases provide an opportunity to compare observed empirical rates of genotype matching with those expected under forensic genetic models. A number of researchers have taken advantage of this opportunity to validate some forensic genetic approaches, particularly to ensure that estimated rates of genotype matching between unrelated individuals are indeed slight overestimates of those observed. However, these studies have also revealed systematic error trends in genotype probability estimates. In this analysis, we investigate these error trends and show how they result from inappropriate implementation of the Balding-Nichols model in the context of database-wide matching. Specifically, we show that in addition to accounting for increased allelic matching between individuals with recent shared ancestry, studies must account for relatively decreased allelic matching between individuals with more ancient shared ancestry.

Leveraging ancestry to improve causal variant identification in exome sequencing for monogenic disorders

Leveraging ancestry to improve causal variant identification in exome sequencing for monogenic disorders

Robert P Brown, Hane Lee, Ascia Eskin, Gleb Kichaev, Kirk E Lohmueller, Bruno Reversade, Stanley F Nelson, Bogdan Pasaniuc
doi: http://dx.doi.org/10.1101/010017

Recent breakthroughs in exome sequencing technology have made possible the identification of many causal variants of monogenic disorders. Although extremely powerful when closely related individuals (e.g. child and parents) are simultaneously sequenced, exome sequencing of individual only cases is often unsuccessful due to the large number of variants that need to be followed-up for functional validation. Many approaches remove from consideration common variants above a given frequency threshold (e.g. 1%), and then prioritize the remaining variants according to their allele frequency, functional, structural and conservation properties. In this work, we present methods that leverage the genetic structure of different populations while accounting for the finite sample size of the reference panels to improve the variant filtering step. Using simulations and real exome data from individuals with monogenic disorders, we show that our methods significantly reduce the number of variants to be followed-up (e.g. a 36% reduction from an average 418 variants per exome when ancestry is ignored to 267 when ancestry is taken into account for case-only sequenced individuals). Most importantly our proposed approaches are well calibrated with respect to the probability of filtering out a true causal variant (i.e. false negative rate, FNR), whereas existing approaches are susceptible to high FNR when reference panel sizes are limited.