SummaryHuman-induced environmental change and habitat fragmentation pose major threats to biodiversity and require active conservation efforts to mitigate their consequences. Genetic rescue through translocation and the introduction of variation into imperiled populations has been argued as a powerful means to preserve, or even increase, the genetic diversity and evolutionary potential of endangered species [1, 2, 3, 4]. However, factors such as outbreeding depression [5, 6] and a reduction in available genetic diversity render the success of such approaches uncertain. An improved evaluation of the consequence of genetic restoration requires knowledge of temporal changes to genetic diversity before and after the advent of management programs. To provide such information, a growing number of studies have included small numbers of genomic loci extracted from historic and even ancient specimens [7, 8]. We extend this approach to its natural conclusion, by characterizing the complete genomic sequences of modern and historic population samples of the crested ibis (Nipponia nippon), an endangered bird that is perhaps the most successful example of how conservation effort has brought a species back from the brink of extinction. Though its once tiny population has today recovered to >2,000 individuals [9], this process was accompanied by almost half of ancestral loss of genetic variation and high deleterious mutation load. We furthermore show how genetic drift coupled to inbreeding following the population bottleneck has largely purged the ancient polymorphisms from the current population. In conclusion, we demonstrate the unique promise of exploiting genomic information held within museum samples for conservation and ecological research.
Hypoxia-Inducible Factor-1 (HIF-1) plays an important role as a transcription factor under hypoxia. It activates numerous genes including those involved in angiogenesis, glucose metabolisms, cell proliferation and cell survival. The HIF-1 alpha subunit is regulated by 2-oxoglutarate (OG)- and Fe(II)-dependent hydroxylases, including Factor Inhibiting HIF-1 (FIH-1). FIH-1 hydroxylates Asn803 of HIF-1 alpha and blocks its interaction with co-activating molecules. Quinol family compounds such as 5-chloro-7-iodo-8-hydroxyquinoline (Clioquinol) have been shown to inhibit the hydroxylation activity of FIH-1. Here we determined the complex crystal structures of FIH-1: Clioquinol and FIH-1: 8-Hydroxyquinoline. Clioquinol and 8-Hydroxyquinoline bind to the active site of FIH-1 by coordinating the Fe(II) ion, thereby inhibiting the binding of a co-substrate, 2OG. Contrary to other known FIH-1 inhibitors that have negative charges, Clioquinol and 8-hydroxyquinoline are neutral in charge and can provide a template for improved inhibitor design that can selectively inhibit FIH-1.
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