Archaic adaptive introgression in TBX15/WARS2

A recent study conducted the first genome-wide scan for selection in Inuit from Greenland using SNP chip data. Here, we report that selection in the region with the second most extreme signal of positive selection in Greenlandic Inuit favored a deeply divergent haplotype that is closely related to the sequence in the Denisovan genome, and was likely introgressed from an archaic population. The region contains two genes, WARS2 and TBX15, and has previously been associated with adipose tissue differentiation and body-fat distribution in humans. We show that the adaptively introgressed allele has been under selection in a much larger geographic region than just Greenland. Furthermore, it is associated with changes in expression of WARS2 and TBX15 in multiple tissues including the adrenal gland and subcutaneous adipose tissue, and with regional DNA methylation changes in TBX15

Three essays in applied microeconomics

This thesis consists of three chapters in Applied Economics, which address three different research questions, using government data from the United Kingdom and Mexico. Chapter 1 examines the impact of an English university reform on educational choices. Using a difference-in-differences approach comparing English-born individuals to other UK nationals before and after the reform, I find that the probability of having vocational secondary school as the highest education level increases between 3 and 6 percentage points once tuition fees in England increase from £3,000 to £9,000. Additionally, I implement a regression discontinuity design to analyze how students in secondary school modify their education content in response to the reform. The first cohort exposed to the modified university fees increased the amount (0.165) and proportion (2.8 percentage points) of secondary school-level vocational qualifications, as well as the probability of attending a vocational course during this stage (7 percentage points). While existing studies have shown that tertiary education choices are responsive to university fees, my findings indicate that these price modifications also alter decisions earlier in the education path, presenting a broader scope of impact for higher education reforms. In Chapter 2, along with my co-authors, I assess the incidence of tax changes in economies where a large share of agents are in the informal sector and therefore do not remit taxes. We study this issue by looking at a large increase in the Value-Added-Tax (VAT) in Mexico in 2014 which only affected areas close to international borders. Using a difference-in-differences approach and rich data on retailers and information on store type to proxy for informality, we consider how the tax increases affected outcomes in the informal and formal retail sectors. We find a 38% pass-through of taxes to formal prices that persists for at least two years, and a smaller (18%) pass-through of taxes to informal prices. Suggestive evidence indicates that informal firms’ sales, profits and number of employees increased thanks to the reform, consistent with the idea that the informal sector gains when taxes increase. Finally, in Chapter 3, I explore how the increase in Mexican VAT studied in Chapter 2 affected electoral outcomes. During 2013, the Mexican president, Enrique Peña Nieto, proposed the equalization of the VAT rate to the General Congress. His political party, the Institutional Revolutionary Party (PRI), held the majority in both chambers, which voted in favor of the law modification. Using a difference-in-differences specification, I examine whether the PRI experienced a change in support in the areas where the tax rate was increased from 11% to 16%. In particular, I analyze the change in vote shares in federal deputy elections, which take place every 3 years. I find that relative to areas where the VAT rate remained at 16%, support for the PRI did not significantly decline in treated regions a year and a half into its implementation. However, I present suggestive evidence that, 4 and a half years after the increase, vote shares for the PRI were reduced in treated areas by 3.2 percentage points

El concepto de representación política en el Congreso General Constituyente de 1824-1827

Resumen temporalmente no disponible. La presente obra no cuenta con resumen provisto por el autor.Fil: Racimo, Fernando Martín. Universidad de Buenos Aires. Facultad de Filosofía y Letras

CADD: predicting the deleteriousness of variants throughout the human genome

Combined Annotation-Dependent Depletion (CADD) is a widely used measure of variant deleteriousness that can effectively prioritize causal variants in genetic analyses, particularly highly penetrant contributors to severe Mendelian disorders. CADD is an integrative annotation built from more than 60 genomic features, and can score human single nucleotide variants and short insertion and deletions anywhere in the reference assembly. CADD uses a machine learning model trained on a binary distinction between simulated de novo variants and variants that have arisen and become fixed in human populations since the split between humans and chimpanzees; the former are free of selective pressure and may thus include both neutral and deleterious alleles, while the latter are overwhelmingly neutral (or, at most, weakly deleterious) by virtue of having survived millions of years of purifying selection. Here we review the latest updates to CADD, including the most recent version, 1.4, which supports the human genome build GRCh38. We also present updates to our website that include simplified variant lookup, extended documentation, an Application Program Interface and improved mechanisms for integrating CADD scores into other tools or applications. CADD scores, software and documentation are available at https://cadd.gs.washington.edu

The complete genome sequence of a Neandertal from the Altai Mountains

We present a high-quality genome sequence of a Neandertal woman from Siberia. We show that her parents were related at the level of half siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neandertal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neandertals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high quality Neandertal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neandertals and Denisovans

Beyond broad strokes: sociocultural insights from the study of ancient genomes

The amount of sequence data obtained from ancient samples has dramatically expanded in the last decade, and so have the type of questions that can now be addressed using ancient DNA. In the field of human history, while ancient DNA has provided answers to long-standing debates about major movements of people, it has also recently begun to inform on other important facets of the human experience. The field is now moving from mostly fixating on large-scale supra-regional studies to also taking a more local perspective, shedding light on socioeconomic processes, inheritance rules, marriage practices and technological diffusion. In this review, we summarize recent studies showcasing these types of insights, focusing on methods used to infer sociocultural aspects of human behaviour. This often involves working across disciplines that have, until recently, evolved in separation. We argue that multidisciplinary dialogue is crucial for a more integrated and richer reconstruction of human history, as it can yield extraordinary insights about past societies, reproductive behaviors and even lifestyle habits that would not have been possible to obtain otherwise

Suficiencia, equidad y efectividad de la infraestructura escolar en América Latina según el TERCE

El objetivo del presente análisis es investigar las características de la infraestructura escolar de la región, utilizando la información de la base de datos del TERCE comparativamente a partir de los conceptos de suficiencia, equidad y efectividad. El documento comienza indagando si los espacios físicos en los cuales estudian los niños y jóvenes latinoamericanos son suficientes y adecuados para garantizar sus aprendizajes. Seguidamente, examina cómo están distribuidos los espacios escolares, tanto según la situación geográfica de los estudiantes como según su nivel socioeconómico y cultural. Por último, explora la efectividad de los recursos físicos de las escuelas, o sea, las asociaciones entre los espacios físicos y los aprendizajes (usando los resultados en las pruebas académicas del TERCE como una aproximación a los mismos)

The spatiotemporal spread of human migrations during the European Holocene

The European continent was subject to two major migrations of peoples during the Holocene: the northwestward movement of Anatolian farmer populations during the Neolithic and the westward movement of Yamnaya steppe peoples during the Bronze Age. These movements changed the genetic composition of the continent’s inhabitants. The Holocene was also characterized by major changes in vegetation composition, which altered the environment occupied by the original hunter-gatherer populations. We aim to test to what extent vegetation change through time is associated with changes in population composition as a consequence of these migrations, or with changes in climate. Using ancient DNA in combination with geostatistical techniques, we produce detailed maps of ancient population movements, which allow us to visualize how these migrations unfolded through time and space. We find that the spread of Neolithic farmer ancestry had a two-pronged wavefront, in agreement with similar findings on the cultural spread of farming from radiocarbon-dated archaeological sites. This movement, however, did not have a strong association with changes in the vegetational landscape. In contrast, the Yamnaya migration speed was at least twice as fast, and coincided with a reduction in the amount of broad-leaf forest and an increase in the amount of pasture and natural grasslands in the continent. We demonstrate the utility of integrating ancient genomes with archaeometric datasets in a spatiotemporal statistical framework, which we foresee will enable future studies of ancient populations movements, and their putative effects on local fauna and flora

A test for ancient selective sweeps and an application to candidate sites in modern humans

We introduce a new method to detect ancient selective sweeps centered on a candidate site. We explored different patterns produced by sweeps around a fixed beneficial mutation, and found that a particularly informative statistic measures the consistency between majority haplotypes near the mutation and genotypic data from a closely related population. We incorporated this statistic into an approximate Bayesian computation (ABC) method that tests for sweeps at a candidate site. We applied this method to simulated data and show that it has some power to detect sweeps that occurred more than 10,000 generations in the past. We also applied it to 1,000 Genomes and Complete Genomics data combined with high-coverage Denisovan and Neanderthal genomes to test for sweeps in modern humans since the separation from the Neanderthal–Denisovan ancestor. We tested sites at which humans are fixed for the derived (i.e., nonchimpanzee allele) whereas the Neanderthal and Denisovan genomes are homozygous for the ancestral allele. We observe only weak differences in statistics indicative of selection between functional categories. When we compare patterns of scaled diversity or use our ABC approach, we fail to find a significant difference in signals of classic selective sweeps between regions surrounding nonsynonymous and synonymous changes, but we detect a slight enrichment for reduced scaled diversity around splice site changes. We also present a list of candidate sites that show high probability of having undergone a classic sweep in the modern human lineage since the split from Neanderthals and Denisovans