Characterizing selection on complex traits through conditional frequency spectra.

Natural selection on complex traits is difficult to study in part due to the ascertainment inherent to genome-wide association studies (GWAS). The power to detect a trait-associated variant in GWAS is a function of frequency and effect size - but for traits under selection, the effect size of a variant determines the strength of selection against it, constraining its frequency. Recognizing the biases inherent to GWAS ascertainment, we propose studying the joint distribution of allele frequencies across populations, conditional on the frequencies in the GWAS cohort.

Century-long timelines of herbarium genomes predict plant stomatal response to climate change.

Dissecting plant responses to the environment is key to understanding whether and how plants adapt to anthropogenic climate change. Stomata, plants' pores for gas exchange, are expected to decrease in density following increased CO concentrations, a trend already observed in multiple plant species. However, it is unclear whether such responses are based on genetic changes and evolutionary adaptation.

Conditional frequency spectra as a tool for studying selection on complex traits in biobanks.

Natural selection on complex traits is difficult to study in part due to the ascertainment inherent to genome-wide association studies (GWAS). The power to detect a trait-associated variant in GWAS is a function of frequency and effect size - but for traits under selection, the effect size of a variant determines the strength of selection against it, constraining its frequency. To account for GWAS ascertainment, we propose studying the joint distribution of allele frequencies across populations, conditional on the frequencies in the GWAS cohort.

Stable population structure in Europe since the Iron Age, despite high mobility.

Ancient DNA research in the past decade has revealed that European population structure changed dramatically in the prehistoric period (14,000-3000 years before present, YBP), reflecting the widespread introduction of Neolithic farmer and Bronze Age Steppe ancestries. However, little is known about how population structure changed from the historical period onward (3000 YBP - present). To address this, we collected whole genomes from 204 individuals from Europe and the Mediterranean, many of which are the first historical period genomes from their region (e.

A genetic history of continuity and mobility in the Iron Age central Mediterranean.

The Iron Age was a dynamic period in central Mediterranean history, with the expansion of Greek and Phoenician colonies and the growth of Carthage into the dominant maritime power of the Mediterranean. These events were facilitated by the ease of long-distance travel following major advances in seafaring. We know from the archaeological record that trade goods and materials were moving across great distances in unprecedented quantities, but it is unclear how these patterns correlate with human mobility.

Mining ancient microbiomes using selective enrichment of damaged DNA molecules.

Background: The identification of bona fide microbial taxa in microbiomes derived from ancient and historical samples is complicated by the unavoidable mixture between DNA from ante- and post-mortem microbial colonizers. One possibility to distinguish between these sources of microbial DNA is querying for the presence of age-associated degradation patterns typical of ancient DNA (aDNA). The presence of uracils, resulting from cytosine deamination, has been detected ubiquitously in aDNA retrieved from diverse sources, and used as an authentication criterion.

Hybridization ddRAD-sequencing for population genomics of nonmodel plants using highly degraded historical specimen DNA.

Species' responses at the genetic level are key to understanding the long-term consequences of anthropogenic global change. Herbaria document such responses, and, with contemporary sampling, provide high-resolution time-series of plant evolutionary change. Characterizing genetic diversity is straightforward for model species with small genomes and a reference sequence.

The origins and adaptation of European potatoes reconstructed from historical genomes.

Potato, one of the most important staple crops, originates from the highlands of the equatorial Andes. There, potatoes propagate vegetatively via tubers under short days, constant throughout the year. After their introduction to Europe in the sixteenth century, potatoes adapted to a shorter growing season and to tuber formation under long days.

nQuire: a statistical framework for ploidy estimation using next generation sequencing.

Background: Intraspecific variation in ploidy occurs in a wide range of species including pathogenic and nonpathogenic eukaryotes such as yeasts and oomycetes. Ploidy can be inferred indirectly - without measuring DNA content - from experiments using next-generation sequencing (NGS). We present nQuire, a statistical framework that distinguishes between diploids, triploids and tetraploids using NGS.

A Robust Framework for Microbial Archaeology.

Microbial archaeology is flourishing in the era of high-throughput sequencing, revealing the agents behind devastating historical plagues, identifying the cryptic movements of pathogens in prehistory, and reconstructing the ancestral microbiota of humans. Here, we introduce the fundamental concepts and theoretical framework of the discipline, then discuss applied methodologies for pathogen identification and microbiome characterization from archaeological samples. We give special attention to the process of identifying, validating, and authenticating ancient microbes using high-throughput DNA sequencing data.

Neandertal and Denisovan DNA from Pleistocene sediments.

Although a rich record of Pleistocene human-associated archaeological assemblages exists, the scarcity of hominin fossils often impedes the understanding of which hominins occupied a site. Using targeted enrichment of mitochondrial DNA, we show that cave sediments represent a rich source of ancient mammalian DNA that often includes traces of hominin DNA, even at sites and in layers where no hominin remains have been discovered. By automation-assisted screening of numerous sediment samples, we detected Neandertal DNA in eight archaeological layers from four caves in Eurasia.

Temporal patterns of damage and decay kinetics of DNA retrieved from plant herbarium specimens.

Herbaria archive a record of changes of worldwide plant biodiversity harbouring millions of specimens that contain DNA suitable for genome sequencing. To profit from this resource, it is fundamental to understand in detail the process of DNA degradation in herbarium specimens. We investigated patterns of DNA fragmentation and nucleotide misincorporation by analysing 86 herbarium samples spanning the last 300 years using Illumina shotgun sequencing.

Contesting the presence of wheat in the British Isles 8,000 years ago by assessing ancient DNA authenticity from low-coverage data.

Contamination with exogenous DNA is a constant hazard to ancient DNA studies, since their validity greatly depend on the ancient origin of the retrieved sequences. Since contamination occurs sporadically, it is fundamental to show positive evidence for the authenticity of ancient DNA sequences even when preventive measures to avoid contamination are implemented. Recently the presence of wheat in the United Kingdom 8000 years before the present has been reported based on an analysis of sedimentary ancient DNA (Smith et al.

Identification of divergent WH2 motifs by HMM-HMM alignments.

Background: The actin cytoskeleton is a hallmark of eukaryotic cells. Its regulation as well as its interaction with other proteins is carefully orchestrated by actin interaction domains. One of the key players is the WH2 motif, which enables binding to actin monomers and filaments and is involved in the regulation of actin nucleation.