Effects of the B chromosome polymorphism of the grasshopper Eyprepocnemis plorans were analyzed in two natural populations. Postmating sexual selection, female fertility, and survival were studied. The B chromosome lacks drive and has no detectable effects on fitness. A neutral B cannot invade a population and establish a polymorphism, but the confidence limits on our estimates cannot exclude the possibility that the polymorphism is maintained by a balance between weak drive and weak selection against individuals with two and three B's. However, other lines of evidence favor the following model of the dynamics of the B in E. plorans. In a newly invaded population, the B has substantial drive, but the evolution of drive suppressor genes in the A chromosomes neutralizes the B drive so that it becomes near-neutral and begins a random walk toward extinction by stochastic loss. Because the B is common by the time drive disappears, the random walk is likely to continue for a long time. If in the course of the random walk a variant B with greater drive appears, then it will displace the original variant, and a new cycle of drive suppression and drift to extinction occurs. A simulation model of this process suggested that the mean time to extinction is proportional to the two-thirds power of the population size; it is much less affected by subpopulation size or the number of populations in a subdivided population.

Improving the prediction of complex diseases by testing for multiple disease-susceptibility genes.

/n and tDepartamento de Genét/ca, Facultad de B/o/ogIa, Un/vers/dad Comp/utense de Madrid, E-28040 Madrid, Spa/n Twenty-eight progeny analyses (PAs) performed on specimens of E. plorans collected from four natural Iberian populations have been informative about the transmission of rare B chromosome types or the de novo origin of some of them. At least ii rare B-types have been found in addition to the predominant ones: B1 in Daimuz, B2 in Jete and Salobreña, and B5 in Fuengirola. The presence in two controlled crosses of one embryo carrying a B-type which was absent in the parents suggests that these B variants (B20 and B ) have originated de novo. Eleven other PAs suggest that new B derivatives are recurrently arising in these populations. The most frequent B chromosome mutation was centromere misdivision that originated four different B-types (B2m1, B110, B210 and Bmjnj). Other rearrangements were pericentric inversions (B211, B212 and B213), inverse tandem fusion (B211), centric fusion (B11) and deletions (B2d1 and B2d2). The four B derivatives produced by centromeric misdivision are significantly eliminated during sexual transmission, most probably owing to deficiencies in the control of chromosome movement by their hemicentromeres. Those derived from translocations showed Mendelian transmission but deletion B variants showed a tendency to elimination. Our results suggest that B chromosome substitution of B1 by B2 in the Salobreña and Jete populations could be achieved by differences in relative transmission efficiency, as in one controlled cross, where the female carried 1 B1 plus 1 B2, B2 was significantly overtransmitted and B1 eliminated.

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A number of females of Locusta migratoria have shown tychoparthenogenetic reproduction (a kind of accidental thelytoky) characterized by: (i) a female-biased primary sex ratio; (ii) the production of embryos with abnormal ploidy levels, mainly haplodiploid mosaics; (iii) a longer time for embryo development; and (iv) the capability of producing female offspring that reproduced in the absence of males. Perfect diploidization is not essential for parthenogenetic embryos to reach the adult stage but a great majority of embryo cells must be diploid to complete properly embryogenesis and hatch. In addition, diploidy is apparently necessary to the ovary of parthenogenetic females so that eggs laid without mating can hatch. Cytological analyses of embryos at different developmental ages have shown that parthenogenetic embryos begin haploid and gradually become diploid, thus passing through a haplodiploid mosaic stage. The most likely mechanism for ploidy restoration is the restitution of the sister products of cleavage mitoses, although our results show that cell fusion could be another mechanism, the relative importance of which remains to be tested in future work. Although parthenogenetic females showed a fecundity comparable to that of sexual females, their reproductive output was significantly lower because of a decrease in the number of embryos per pod and a consequent decrease in the rate of embryo production.