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Over the past few years several methodological and data-driven advances have greatly improved our ability to robustly detect genomic signatures of selection in humans. New methods applied to large samples of present-day genomes provide increased power, while ancient DNA allows precise estimation of timing and tempo. However, despite these advances, we are still limited in our ability to translate these signatures into understanding about which traits were actually under selection, and why. Combining information from different populations and timescales may allow interpretation of selective sweeps. Other modes of selection have proved more difficult to detect. In particular, despite strong evidence of the polygenicity of most human traits, evidence for polygenic selection is weak, and its importance in recent human evolution remains unclear. Balancing selection and archaic introgression seem important for the maintenance of potentially adaptive immune diversity, but perhaps less so for other traits., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

For the purpose of this review, 'time-lapse' refers to the reconstruction of ancestral (in this case dinosaur) karyotypes using genome assemblies of extant species. Such reconstructions are only usually possible when genomes are assembled to 'chromosome level' i.e. a complete representation of all the sequences, correctly ordered contiguously on each of the chromosomes. Recent paleontological evidence is very clear that birds are living dinosaurs, the latest example of dinosaurs emerging from a catastrophic extinction event. Non-avian dinosaurs (ever present in the public imagination through art, and broadcast media) emerged some 240 million years ago and have displayed incredible phenotypic diversity. Here we report on our recent studies to infer the overall karyotype of the Theropod dinosaur lineage from extant avian chromosome level genome assemblies. Our work first focused on determining the likely karyotype of the avian ancestor (most likely a chicken-sized, two-legged, feathered, land dinosaur from the Jurassic period) finding karyotypic similarity to the chicken. We then took the work further to determine the likely karyotype of the bird-lizard ancestor and the chromosomal changes (chiefly translocations and inversions) that occurred between then and modern birds. A combination of bioinformatics and cross-species fluorescence in situ hybridization (zoo-FISH) uncovered a considerable number of translocations and fissions from a 'lizard-like' genome structure of 2n = 36-46 to one similar to that of soft-shelled turtles (2n = 66) from 275 to 255 million years ago (mya). Remarkable karyotypic similarities between some soft-shelled turtles and chicken suggests that there were few translocations from the bird-turtle ancestor (plus ∼7 fissions) through the dawn of the dinosaurs and pterosaurs, through the theropod linage and on to most to modern birds. In other words, an avian-like karyotype was in place about 240mya when the dinosaurs and pterosaurs first emerged. We mapped 49 chromosome inversions from then to the present day, uncovering some gene ontology enrichment in evolutionary breakpoint regions. This avian-like karyotype with its many (micro)chromosomes provides the basis for variation (the driver of natural selection) through increased random segregation and recombination. It may therefore contribute to the ability of dinosaurs to survive multiple extinction events, emerging each time as speciose and diverse., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The formalization of the idea of "Regulatory Genome" is a recent one. However, it stems from a long tradition in the study of how the genetic information is transferred between generations. Theodore Boveri suggested for the first time that the whole genome participates in the shaping of individuals. Through a long lineage of researchers, we have learned how this whole-genome activity is regulated, in space and time. It is, however, due to the insights and experimental approaches taken by different researchers, among them Eric Davidson and associates, that we understand the mechanistic basis of this regulation. Whole batteries of regulatory genes interact through their cis-regulatory modules, generating a precise pattern of cross-controlled gene activity (Gene Regulatory Networks). How these genes are deployed in development and evolution has become an area of vibrant research. Here we revisit the history of this intellectual endeavour, taking as key defining points along this historical trajectory the contributions of Theodor Boveri and Eric Davidson., (Copyright © 2018 Elsevier B.V. All rights reserved.)

DNA sequencing has been characterised by scholars and life scientists as an example of 'big', 'fast' and 'automated' science in biology. This paper argues, however, that these characterisations are a product of a particular interpretation of what sequencing is, what I call 'thin sequencing'. The 'thin sequencing' perspective focuses on the determination of the order of bases in a particular stretch of DNA. Based upon my research on the pig genome mapping and sequencing projects, I provide an alternative 'thick sequencing' perspective, which also includes a number of practices that enable the sequence to travel across and be used in wider communities. If we take sequencing in the thin manner to be an event demarcated by the determination of sequences in automated sequencing machines and computers, this has consequences for the historical analysis of sequencing projects, as it focuses attention on those parts of the work of sequencing that are more centralised, fast (and accelerating) and automated. I argue instead that sequencing can be interpreted as a more open-ended process including activities such as the generation of a minimum tile path or annotation, and detail the historiographical and philosophical consequences of this move., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Research on bacteriophages has significantly enhanced our understanding of molecular biology, the genomes of prokaryotic cells, and viral ecology. Phages and lysins offer a viable alternative to the declining utility of antibiotics in this post-antibiotic era. They also provide ideal teaching tools for genomics and bioinformatics. This article touches on the first 100 years of phage research with the author commenting on what he thinks are the highlights, and what needs to be addressed., (Copyright © 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Genomic technologies are now being applied to reproductive genetic screening. Circulating cell-free DNA testing in pregnancy for fetal chromosomal abnormalities is becoming more widely used as a screening test, and expanded carrier screening for autosomal and X-linked recessive conditions for more than a hundred conditions is available to couples for testing before and during pregnancy. These are most typically available as a commercial test. The purpose of reproductive genetic screening is to facilitate autonomous reproductive choices. Previous studies would suggest that many women do not make informed decisions about prenatal genetic screening, and the introduction of genomic technologies has generally added to the ethical debate. Appropriate pre-test genetic counselling is recommended, and healthcare providers should include information that is balanced, accurate and up-to-date, comprising written and/or e-learning tools, as well as providing psychosocial support so that couples consider the pros and cons of being tested and can make informed decisions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

One hundred years of the Hubrecht Institute were celebrated in May 2016 with the organization of a one-day symposium "From embryos to stem cells" on the Uithof Campus, Utrecht, the Netherlands. Nine distinguished speakers were invited. They all represent a research branch originating from the passion of Institute founder, Ambrosius Hubrecht, for embryology:, regulation of gene expression, genome structure and function, embryonic and adult stem cells, nuclear reprogramming, and understanding cancer and other diseases using model organisms. The centennial symposium not only retraced the history of the Institute and of modern developmental biology, but was also a tribute to basic research. From there, avenues to therapeutics are being developed and implemented. The symposium was organized, introduced and chaired by Jeroen den Hertog and Alexander van Oudenaarden, the present Directors of the Institute, who also stand on Hubrecht's shoulders., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The trans-Atlantic slave trade brought millions of Africans to the New World. Advances in genomics are providing novel insights into the history and health of Africans and the diasporan populations. Recent examples reviewed here include the unraveling of substantial hunter-gatherer and 'Eurasian' admixtures across sub-Saharan Africa, expanding our understanding of ancestral African genetics; the global ubiquity of mixed ancestry; the revealing of African ancestry in Latin Americans that likely derived from the slave trade; and understanding of the ancestral backgrounds of APOL1 and LPL found to influence kidney disease and lipid levels, respectively, providing specific insights into disease etiology and health disparities., (Published by Elsevier Ltd.)

This symposium marks the achievement of a transformation in the history of science. Whereas in the 1960s, the study of modern developments was marginal to the field, it has now become a key part of the discipline's central concerns. The contrast between this conference and a 1960 symposium is illuminating. The paper reflects on the tensions over the future direction of the discipline expressed at the 1974 semi-centenary conference of the History of Science Society. Today, genomics with its vast demand for resources and its challenges to traditional boundaries is not untypical of a wide range of scientific activities. Its study can serve as a pioneering case study interesting for itself and important for a wider understanding of science. Papers at this meeting show the implications for the understanding of methods, appropriate targets of study, the interpretation of images and the preservation of archives., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In this paper I track the history of post-1945 human genetics and genomics emphasizing the importance of ideas about risk to the scientific study and medical management of human heredity. Drawing on my own scholarship as it is refracted through important new work by other scholars both junior and senior, I explore how radiation risk and then later disease risk mattered to the development of genetics and genomics, particularly in the United States. In this context I excavate one of the central ironies of post-war human genetics: while studies of DNA as the origin and cause of diseases have been lavishly supported by public institutions and private investment around the world, the day-to-day labor of intensive clinical innovation has played a far more important role in the actual human experience of genetic disease and genetic risk for affected families. This has implications for the archival record, where clinical interactions are less readily accessible to historians. This paper then suggests that modern genomics grew out of radiation risk; that it was and remains a risk assessment science; that it is temporally embedded as a form of both prediction and historical reconstruction; and that it has become a big business focused more on risk and prediction (which can be readily marketed) than on effective clinical intervention., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In this paper, I propose a strategy for navigating newly available archives in the study of late-twentieth century genomics. I demonstrate that the alleged 'explosion of data' characteristic of genomics-and of contemporary science in general-is not a new problem and that historians of earlier periods have dealt with information overload by relying on the 'perspective of time': the filtering effect the passage of time naturally exerts on both sources and memories. I argue that this reliance on the selective capacity of time results in inheriting archives curated by others and, consequently, poses the risk of reifying ahistorical scientific discourses. Through a preliminary examination of archives documenting early attempts at mapping and sequencing the human genome, I propose an alternative approach, in which historians proactively problematize and improve available sources. This approach provides historians with a voice in the socio-political management of scientific heritage and advances methodological innovations in the use of oral histories. It also provides a narrative framework in which to address big science initiatives by following second order administrators, rather than individual scientists. The new genomic archives thus represent an opportunity for historians to take an active role in current debates concerning 'big data' and critically embed the humanities in pressing global problems., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In the mid-1990s, the company Human Genome Sciences submitted three potentially revolutionary patent applications to the US Patent and Trademark Office, each of which claimed the entire genome sequence of a microorganism. The patent examiners, however, objected to these applications, and after negotiation they were eventually re-written to resemble more traditional gene patents. In this paper, which is based on a study of the patent examination files, we examine the reasons why these patent applications were unsuccessful in their original form. We show that with respect to utility and novelty, the patent attorney's case built on an understanding of the genome as a computer-related invention. The patent examiners did not object to the patenting of complete genome sequences as computer-related inventions on moral grounds or in terms of the distinction between a discovery and an invention. Instead, their objections were based on classification, rules and procedure. Rather than patent examiners having a notion of a genome that should not be patented, the notion of a 'genome', and the ways in which it may be different from a 'gene', played no role in these debates. We discuss the consequences of our findings for patenting in the biosciences.