Synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) generates combinatorial genomic diversity through rearrangements at designed recombinase sites. We applied SCRaMbLE to yeast synthetic chromosome arm synIXR (43 recombinase sites) and then used a computational pipeline to infer or unscramble the sequence of recombinations that created the observed genomes. Deep sequencing of 64 synIXR SCRaMbLE strains revealed 156 deletions, 89 inversions, 94 duplications, and 55 additional complex rearrangements; several duplications are consistent with a double rolling circle mechanism. Every SCRaMbLE strain was unique, validating the capability of SCRaMbLE to explore a diverse space of genomes. Rearrangements occurred exclusively at designed loxPsym sites, with no significant evidence for ectopic rearrangements or mutations involving synthetic regions, the 99% nonsynthetic nuclear genome, or the mitochondrial genome. Deletion frequencies identified genes required for viability or fast growth. Replacement of 3′ UTR by non-UTR sequence had surprisingly little effect on fitness. SCRaMbLE generates genome diversity in designated regions, reveals fitness constraints, and should scale to simultaneous evolution of multiple synthetic chromosomes.

BackgroundNearly one-quarter of all avian species is either threatened or nearly threatened. Of these, 73 species are currently being rescued from going extinct in wildlife sanctuaries. One of the previously most critically-endangered is the crested ibis, Nipponia nippon. Once widespread across North-East Asia, by 1981 only seven individuals from two breeding pairs remained in the wild. The recovering crested ibis populations thus provide an excellent example for conservation genomics since every individual bird has been recruited for genomic and demographic studies.ResultsUsing high-quality genome sequences of multiple crested ibis individuals, its thriving co-habitant, the little egret, Egretta garzetta, and the recently sequenced genomes of 41 other avian species that are under various degrees of survival threats, including the bald eagle, we carry out comparative analyses for genomic signatures of near extinction events in association with environmental and behavioral attributes of species. We confirm that both loss of genetic diversity and enrichment of deleterious mutations of protein-coding genes contribute to the major genetic defects of the endangered species. We further identify that genetic inbreeding and loss-of-function genes in the crested ibis may all constitute genetic susceptibility to other factors including long-term climate change, over-hunting, and agrochemical overuse. We also establish a genome-wide DNA identification platform for molecular breeding and conservation practices, to facilitate sustainable recovery of endangered species.ConclusionsThese findings demonstrate common genomic signatures of population decline across avian species and pave a way for further effort in saving endangered species and enhancing conservation genomic efforts.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-014-0557-1) contains supplementary material, which is available to authorized users.

Background: Nearly one-quarter of all avian species is either threatened or nearly threatened. Of these, 73 species are currently being rescued from going extinct in wildlife sanctuaries. One of the previously most critically-endangered is the crested ibis, Nipponia nippon. Once widespread across North-East Asia, by 1981 only seven individuals from two breeding pairs remained in the wild. The recovering crested ibis populations thus provide an excellent example for conservation genomics since every individual bird has been recruited for genomic and demographic studies. Results: Using high-quality genome sequences of multiple crested ibis individuals, its thriving co-habitant, the little egret, Egretta garzetta, and the recently sequenced genomes of 41 other avian species that are under various degrees of survival threats, including the bald eagle, we carry out comparative analyses for genomic signatures of near extinction events in association with environmental and behavioral attributes of species. We confirm that both loss of genetic diversity and enrichment of deleterious mutations of protein-coding genes contribute to the major genetic defects of the endangered species. We further identify that genetic inbreeding and loss-of-function genes in the crested ibis may all constitute genetic susceptibility to other factors including long-term climate change, over-hunting, and agrochemical overuse. We also establish a genome-wide DNA identification platform for molecular breeding and conservation practices, to facilitate sustainable recovery of endangered species.Conclusions: These findings demonstrate common genomic signatures of population decline across avian species and pave a way for further effort in saving endangered species and enhancing conservation genomic efforts.

This paper is the result of a collaborative work between researchers based in UK, Italy, China and Brazil, and aims at providing a comprehensive review of practices and meanings of Non--Invasive Prenatal Testing (NIPT) in these countries, while also highlighting the ethical implications that NIPT poses. In the first part of this paper we describe how the technology is being integrated into the 'moral economy' of prenatal testing in the different countries we analysed. The uses of NIPT differ greatly in the countries we analysed.In the second section of the paper we position NIPT within the trajectory of prenatal diagnosis that, displays the role of conflicting values and often incommensurable moral economies in the emergence of new technologies, and in their transformation into routine medical procedures. The two 'often incommensurable moral economies' are women's autonomy and individual--centred medicine, as emphasised in gynaecologists and midwives/obstetricians' public discourse; and considerations about the cost/efficacy of long--term care for people with Down Syndrome or other chromosomal--related disabilities as emphasized in public health discourses. We discuss how these two contrasting narratives are also at play (more or less covertly) in the discourses around NIPT. We then consider some of the ethical issues raised by NIPT, including the argument that NIPT will lead to a harmful bias towards people with Down Syndrome and to an increase in termination rates; and the ethical issues raised possible incidental findings resulting from a maternal chromosomal mosaicisms due to an anomalous cellular line, and other hidden abnormalities in one of the parents, including genetic diseases with late expressions in life. We note how the counselling step following incidental finding will be of the utmost importance and that in many countries, including the ones we analysed, doctors and healthcare professionals are not adequately prepared for it. We conclude that it is important that bioethics scholarship engages proactively with the ethical issues that arise at the nexus of these conflicting values and moral economies, especially as future evolutions of NIPT combined with whole genome sequencing (WGS) will affect women's reproductive decisions, and shape the scope of their reproductive choices, in a way that will lead to a completely new level of 'supervision', 'management' and 'scrutiny' of human foetuses and pregnant women. Accepted for publication June 30, 2016 Forthcoming September 20163 French key--words (Mot--clefs): diagnostique prénatal, tests prénataux non invasifs, NIPT, maladie génétique French AbstractCet article est le résultat d'une collaboration entre des chercheurs qui ont étudié l'évolution du diagnostique prénatal au Royaume Uni, en Italie, en Chine et au Brésil. Il passe en revue les pratiques liées à l'introduction des tests prénataux non invasifs (NIPT) dans ces pays, et discute les questions éthiques liées à l'introduction de cette nouvelle approche diagnostique. En Chine, en Italie, au Royaume ...