Analysis of inbreeding in a colonizing population of Drosophila subobscura

An analysis of the effects of inbreeding on the genetic structure of a colonizing population of Drosophila subobscura has been carried out. Species of Drosophila, particularly D. subobscura, may have lethal alleles associated with chromosomal inversions and our aim was to assess the extent to which the genome is balanced in this way. The frequencies of chromosomal inversions were compared between a large population and a set of 72 lines that were maintained by brother-sister mating for 10 generations. Fisher's matrix method was used to calculate the expected homozygosity in these inbred lines for 5 allozyme loci (Aph, Hk-1, Lap, Odh, and Pept-1) used as markers of large chromosomal segments. Furthermore, the expected rates of fixation corresponding to these allozyme loci were also calculated. The results show that the amount of homozygosis observed did not differ significantly from expectations (with the corresponding loss of lines as a consequence of the reduction in viability). However, two deviations from strict neutrality were observed: there was a heterozygote excess at the Lap locus, and the frequency of the O ₅ inversion (always associated with a lethal gene in colonizing populations) was higher than expected.     

Introduction

The only concrete basis for the discontinuous and hierarchical organization of extant organisms lies in their genealogical (i. e. germ line) relationships. Individuals and populations of common descent are called sib or stirps. Ideally, systematic classification is based on the formulas: (1) sib + taxonomic category + name = taxon, and (2) divergent genealogy of sibs + hierarchy of taxonomic categories + names = taxonomic system (Fig. 1).Presented at the symposium Speciation and the Species Concept during the XIIth International Botanical Congress, Leningrad, July 8, 1975.     

Managing the middle: A shift in conservation priorities based on the global human modification gradient

An increasing number of international initiatives aim to reconcile development with conservation. Crucial to successful implementation of these initiatives is a comprehensive understanding of the current ecological condition of landscapes and their spatial distributions. Here, we provide a cumulative measure of human modification of terrestrial lands based on modeling the physical extents of 13 anthropogenic stressors and their estimated impacts using spatially explicit global datasets with a median year of 2016. We quantified the degree of land modification and the amount and spatial configuration of low modified lands (i.e., natural areas relatively free from human alteration) across all ecoregions and biomes. We identified that fewer unmodified lands remain than previously reported and that most of the world is in a state of intermediate modification, with 52% of ecoregions classified as moderately modified. Given that these moderately modified ecoregions fall within critical land use thresholds, we propose that they warrant elevated attention and require proactive spatial planning to maintain biodiversity and ecosystem function before important environmental values are lost.     

Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008–2019)

Cyclooxygenase-2 is a very important physiological enzyme playing key roles in various biological functions especially in the mechanism of pain and inflammation, among other roles, making it a molecule of high interest to the pharmaceutical community as a target. COX 2 enzyme is induced only during inflammatory processes or cancer and reflects no role in the guarding stomach lining. Thus, selective COX-2 inhibition can significantly reduce the adverse effects including GI tract damage and hepatotoxic effects of traditional NSAIDs like aspirin, ibuprofen, etc. Recent developments on COX-2 inhibitors is primarily focused on improving the selectivity index of the drug towards COX-2 along with enhancing the potency of the drug by modifying the scaffolds of Coxibs currently in the market like Celecoxib, Indomethacin, Oxaprozin, etc. We have reported the progress on new COX-2 inhibitors in the last decade (2008–2019) focussing on five heterocyclic rings- Pyrazole, Indole, Oxazole, Pyridine and Pyrrole. The addition of various moieties to these core rings and their structure-activity relationship along with their molecular modelling data have been explored in the article. This review aims to aid medicinal chemists in the design and discovery of better COX-2 inhibitors constructed on these five heterocyclic pharmacophores.     

Life history variation in gametophyte populations of the moss Ceratodon purpureus (Ditrichaceae)

The life cycles of mosses and other bryophytes are unique among land plants in that the haploid gametophyte stage is free-living and the diploid sporophyte stage is ephemeral and completes its development attached to the maternal gametophyte. Despite predictions that populations of haploids might contain low levels of genetic variation, moss populations are characterized by substantial variation at isozyme loci. The extent to which this is indicative of ecologically important life history variation is, however, largely unknown. Gametophyte plants from two populations of the moss Ceratodon purpureus were grown from single-spore isolates in order to assess variation in growth rates, biomass accumulation, and reproductive output. The data were analyzed using a nested analysis of variance, with haploid sib families (gametophytes derived from the same sporophyte) nested within populations. High levels of life history variation were observed within both populations, and the populations differed significantly in both growth and reproductive characteristics. Overall gametophytic sex ratios did not depart significantly from 1:1 within either population, but there was significant variation among families in both populations for progeny sex ratio. Some families produced predominantly male gametophytes, while others yielded predominantly females. Because C. purpureus has a chromosomal mechanism of sex determination, these observations suggest differential (but unpredictable) germination of male and female spores. Life history observations showed that male and female gametophytes are dimorphic in size, maturation rates, and reproductive output.     

Sib mating designs for mapping quantitative trait loci

The power to separate the variance of a quantitative trait locus (QTL) from the polygenic variance is determined by the variability of genes identical by descent (IBD) at the QTL. This variability may increase with inbreeding. Selfing, the most extreme form of inbreeding, increases the variability of the IBD value shared by siblings, and thus has a higher efficiency for QTL mapping than random mating. In self-incompatible organisms, sib mating is the closest form of inbreeding. Similar to selfing, sib mating may also increase the power of QTL detection relative to random mating. In this study, we develop an IBD-based method under sib mating designs for QTL mapping. The efficiency of sib mating is then compared with random mating. Monte Carlo simulations show that sib mating designs notably increase the power for QTL detection. When power is intermediate, the power to detect a QTL using full-sib mating is, on average, 7% higher than under random mating. In addition, the IBD-based method proposed in this paper can be used to combine data from multiple families. As a result, the estimated QTL parameters can be applied to a wide statistical inference space relating to the entire reference population. This revised version was published online in July 2006 with corrections to the Cover Date.     

The effect of halogen atom on the molecular quadratic nonlinearity of half sandwich complexes in the presence of an acceptor

Half sandwich complexes of the type [CpM(CO)_nX] {X = Cl, Br, I; If, M = Fe, Ru; n = 2 and if M = Mo; n = 3} and [CpNiPPh₃X] {X = Cl, Br, I} have been synthesized and their second order molecular nonlinearity (β) measured at 1064 nm in CHCl₃ by the hyper-Rayleigh scattering technique. Iron complexes consistently display larger β values than ruthenium complexes while nickel complexes have marginally larger β values than iron complexes. In the presence of an acceptor ligand such as CO or PPh₃, the role of the halogen atom is that of a π donor. The better overlap of Cl orbitals with Fe and Ni metal centres make Cl a better π donor than Br or I in the respective complexes. Consequently, M-π interaction is stronger in Fe/Ni-Cl complexes. The value of β decreases as one goes down the halogen group. For the complexes of 4d metal ions where the metal-ligand distance is larger, the influence of π orbital overlap appears to be less important, resulting in moderate changes in β as a function of halogen substitution.     

Analysis and purification of IgG4 bispecific antibodies by a mixed-mode chromatography

Therapeutic non-hinge-modified IgG4 molecules form bispecific hybrid antibodies with endogenous human IgG4 molecules via a process known as Fab-arm exchange (or called half molecule exchange). Analysis of the bispecific hybrids is critical for studies of half molecule exchange. A number of analytical methods are available to detect IgG4 hybrids. These methods mostly necessitate labeling or alteration of the model IgG4 molecules, or rely on time-consuming immunoassays and mass spectrometry. In addition, these methods do not allow isolation of hybrid antibodies. We report here the only analytical method to date that relies on chromatographic separation for detection of hybrids formed from intact antibodies in their native forms using pembrolizumab as an example. This method employs a mixed-mode chromatography using a Sepax Zenix SEC-300 column to separate a bispecific hybrid from the parental antibodies. The simultaneous quantitative monitoring of the newly formed hybrid and parental antibodies was achieved by UV absorption and/or protein fluorescence. The bispecific hybrid antibodies were purified with the same method for further biochemical characterization. The method has allowed monitoring of half molecule exchange between a human serum IgG4 and a tested IgG4 molecule, and has been implemented for the analysis of in vitro as well as in vivo samples.     

Experimental evolution of the genetic load and its implications for the genetic basis of inbreeding depression

The degree to which, and rapidity with which, inbreeding depression can be purged from a population has important implications for conservation biology, captive breeding practices, and invasive species biology. The degree and rate of purging also informs us regarding the genetic mechanisms underlying inbreeding depression. We examine the evolution of mean survival and inbreeding depression in survival following serial inbreeding in a seed-feeding beetle, Stator limbatus, which shows substantial inbreeding depression at all stages of development. We created two replicate serially inbred populations perpetuated by full-sib matings and paired with outbred controls. The genetic load for the probability that an egg produces an adult was purged at approximately 0.45-0.50 lethal equivalents/generation, a reduction of more than half after only three generations of sib-mating. After serial inbreeding we outcrossed all beetles then measured (1) larval survival of outcrossed beetles and (2) inbreeding depression. Survival of outcrossed beetles evolved to be higher in the serially inbred populations for all periods of development. Inbreeding depression and the genetic load were significantly lower in the serially inbred than control populations. Inbreeding depression affecting larval survival of S. limbatus is largely due to recessive deleterious alleles of large effect that can be rapidly purged from a population by serial sib-mating. However, the effectiveness of purging varied among the periods of egg/larval survival and likely varies among other unstudied fitness components. This study presents novel results showing rapid and extensive purging of the genetic load, specifically a reduction of as much as 72% in only three generations of sib-mating. However, the high rate of extinction of inbred lines, despite the lines being reared in a benign laboratory environment, indicates that intentional purging of the genetic load of captive endangered species will not be practical due to high rates of subpopulation extinction.