Evolving while invading: rapid adaptive evolution in juvenile development time for a biological control organism colonizing a high-elevation environment

We report evidence of adaptive evolution in juvenile development time on a decadal timescale for the cinnabar moth Tyria jacobaeae (Lepidoptera: Arctiidae) colonizing new habitats and hosts from the Willamette Valley to the Coast Range and Cascades Mountains in Oregon. Four lines of evidence reveal shorter egg to pupa juvenile development times evolved in the mountains, where cooler temperatures shorten the growing season: (i) field observations showed that the mountain populations have shorter phenological development; (ii) a common garden experiment revealed genetic determination of phenotypic differences in juvenile development time between Willamette Valley and mountain populations correlated with the growing season; (iii) a laboratory experiment rearing offspring from parental crosses within and between Willamette Valley and Cascades populations demonstrated polygenic inheritance, high heritability, and genetic determination of phenotypic differences in development times; and (iv) statistical tests that exclude random processes (founder effect, genetic drift) in favor of natural selection as explanations for observed differences in phenology. These results support the hypothesis that rapid adaptation to the cooler mountain climate occurred in populations established from populations in the warmer valley climate. Our findings should motivate regulators to require evaluation of evolutionary potential of candidate biological control organisms prior to release.Keywords: phenology, heritability, Tyria jacobaeae, natural selection, quantitative trait, contemporary evolution, development time, Senecio triangulari

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Evolving while invading: rapid adaptive evolution in juvenile development time for a biological control organism colonizing a high-elevation environment

We report evidence of adaptive evolution in juvenile development time on a decadal timescale for the cinnabar moth Tyria jacobaeae (Lepidoptera: Arctiidae) colonizing new habitats and hosts from the Willamette Valley to the Coast Range and Cascades Mountains in Oregon. Four lines of evidence reveal shorter egg to pupa juvenile development times evolved in the mountains, where cooler temperatures shorten the growing season: (i) field observations showed that the mountain populations have shorter phenological development; (ii) a common garden experiment revealed genetic determination of phenotypic differences in juvenile development time between Willamette Valley and mountain populations correlated with the growing season; (iii) a laboratory experiment rearing offspring from parental crosses within and between Willamette Valley and Cascades populations demonstrated polygenic inheritance, high heritability, and genetic determination of phenotypic differences in development times; and (iv) statistical tests that exclude random processes (founder effect, genetic drift) in favor of natural selection as explanations for observed differences in phenology. These results support the hypothesis that rapid adaptation to the cooler mountain climate occurred in populations established from populations in the warmer valley climate. Our findings should motivate regulators to require evaluation of evolutionary potential of candidate biological control organisms prior to release.We report evidence of adaptive evolution in juvenile development time on a decadal timescale for the cinnabar moth Tyria jacobaeae (Lepidoptera: Arctiidae)colonizing new habitats and hosts from the Willamette Valley to the Coast Rangeand Cascades Mountains in Oregon. Four lines of evidence reveal shorter egg topupa juvenile development times evolved in the mountains, where cooler temperatures shorten the growing season: (i) ?eld observations showed that themountain populations have shorter phenological development; (ii) a commongarden experiment revealed genetic determination of phenotypic differences injuvenile development time between Willamette Valley and mountain populationscorrelated with the growing season; (iii) a laboratory experiment rearing offspring from parental crosses within and between Willamette Valley and Cascadespopulations demonstrated polygenic inheritance, high heritability, and geneticdetermination of phenotypic differences in development times; and (iv) statisticaltests that exclude random processes (founder effect, genetic drift) in favor of natural selection as explanations for observed differences in phenology. These resultssupport the hypothesis that rapid adaptation to the cooler mountain climateoccurred in populations established from populations in the warmer valley climate. Our ?ndings should motivate regulators to require evaluation of evolutionary potential of candidate biological control organisms prior to release

The Statistical Analysis of Insect Phenology

Weintroduce two simple methods for the statistical comparison of the temporal pattern of life-cycle events between two populations. The methods are based on a translation of stagefrequency data into individual Ôtimes in stageÕ. For example, if the stage-k individuals in a set of samples consist of three individuals counted at time t1 and two counted at time t₂, the observed times in stage k would be (t₁, t₁, t₁, t₂, t₂). Times in stage then can be compared between two populations by performing stage-speciÞc t-tests or by testing for equality of regression lines of time versus stage between the two populations. Simulations show that our methods perform at close to the nominal level, have good power against a range of alternatives, and have much better operating characteristics than a widely-used phenology model from the literature.Keywords: phenology, t-test, logistic, Tyria jacobaea

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. US National Institutes of Health and Operation Warp Spee