Hybrid Breakdown in Cichlid Fish

Studies from a wide diversity of taxa have shown a negative relationship between genetic compatibility and the divergence time of hybridizing genomes. Theory predicts the main breakdown of fitness to happen after the F1 hybrid generation, when heterosis subsides and recessive allelic (Dobzhansky-Muller) incompatibilities are increasingly unmasked. We measured the fitness of F2 hybrids of African haplochromine cichlid fish bred from species pairs spanning several thousand to several million years divergence time. F2 hybrids consistently showed the lowest viability compared to F1 hybrids and non-hybrid crosses (crosses within the grandparental species), in agreement with hybrid breakdown. Especially the short- and long-term survival (2 weeks to 6 months) of F2 hybrids was significantly reduced. Overall, F2 hybrids showed a fitness reduction of 21% compared to F1 hybrids, and a reduction of 43% compared to the grandparental, non-hybrid crosses. We further observed a decrease of F2 hybrid viability with the genetic distance between grandparental lineages, suggesting an important role for negative epistatic interactions in cichlid fish postzygotic isolation. The estimated time window for successful production of F2 hybrids resulting from our data is consistent with the estimated divergence time between the multiple ancestral lineages that presumably hybridized in three major adaptive radiations of African cichlids.     

Hybridization and speciation

Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near‐instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky–Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock‐on effects on speciation both within and outside regions of hybridization.     

Heterosis in hybrids within and between yeast species

The performance of hybrids relative to their parents is an important factor in speciation research. We measured the growth of 46 Saccharomyces yeast F1 interspecific and intraspecific hybrids, relative to the growth of each of their parents, in pairwise competition assays. We found that the growth of a hybrid relative to the average of its parents, a measure of mid‐parent heterosis, correlated with the difference in parental growth relative to their hybrid, a measure of phenotypic divergence, which is consistent with simple complementation of low fitness alleles in one parent by high fitness alleles in the other. Interspecific hybrids showed stronger heterosis than intraspecific hybrids. To manipulate parental phenotypic divergence independently of genotype, we also measured the competitive growth of a single interspecific hybrid relative to its parents in 12 different environments. In these assays, we not only identified a strong relationship between parental phenotypic divergence and mid‐parent heterosis as before, but, more tentatively, a weak relationship between phenotypic divergence and best‐parent heterosis, suggesting that complementation of deleterious mutations was not the sole cause of interspecific heterosis. Our results show that mating between different species can be beneficial, and demonstrate that competition assays between parents and offspring are a useful way to study the evolutionary consequences of hybridization.     

Modulation of immune responses by Plasmodium falciparum infection in asymptomatic children living in the endemic region of Mbita,western Kenya

Individuals living in malaria endemic areas become clinically immune after multiple re-infections over time and remain infected without apparent symptoms. However, it is unclear why a long period is required to gain clinical immunity to malaria, and how such immunity is maintained. Although malaria infection is reported to induce inhibition of immune responses, studies on asymptomatic individuals living in endemic regions of malaria are relatively scarce. We conducted a cross-sectional study of immune responses in asymptomatic school children aged 4–16 years living in an area where Plasmodium falciparum and Schistosoma mansoni infections are co-endemic in Kenya. Peripheral blood mononuclear cells were subjected to flow cytometric analysis and cultured to determine proliferative responses and cytokine production. The proportions of cellular subsets in children positive for P. falciparum infection at the level of microscopy were comparable to the negative children, except for a reduction in central memory-phenotype CD8⁺ T cells and natural killer cells. In functional studies, the production of cytokines by peripheral blood mononuclear cells in response to P. falciparum crude antigens exhibited strong heterogeneity among children. In addition, production of IL-2 in response to anti-CD3 and anti-CD28 monoclonal antibodies was significantly reduced in P. falciparum-positive children as compared to -negative children, suggesting a state of unresponsiveness. These data suggest that the quality of T cell immune responses is heterogeneous among asymptomatic children living in the endemic region of P. falciparum, and that the responses are generally suppressed by active infection with Plasmodium parasites.     

Disruptive sexual selection on male nuptial coloration in an experimental hybrid population of cichlid fish

Theory suggests that genetic polymorphisms in female mating preferences may cause disruptive selection on male traits, facilitating phenotypic differentiation despite gene flow, as in reinforcement or other models of speciation with gene flow. Very little experimental data have been published to test the assumptions regarding the genetics of mate choice that such theory relies on. We generated a population segregating for female mating preferences and male colour dissociated from other species differences by breeding hybrids between species of the cichlid fish genus Pundamilia. We measured male mating success as a function of male colour. First, we demonstrate that non-hybrid females of both species use male nuptial coloration for choosing mates, but with inversed preferences. Second, we show that variation in female mating preferences in an F2 hybrid population generates a quadratic fitness function for male coloration suggestive of disruptive selection: intermediate males obtained fewer matings than males at either extreme of the colour range. If the genetics of female mate choice in Pundamilia are representative for those in other species of Lake Victoria cichlid fish, it may help explain the origin and maintenance of phenotypic diversity despite some gene flow.     

The Stem Region of Premembrane Protein Plays an Important Role in the Virus Surface Protein Rearrangement during Dengue Maturation

Newly assembled dengue viruses (DENV) undergo maturation to become infectious particles. The maturation process involves major rearrangement of virus surface premembrane (prM) and envelope (E) proteins. The prM-E complexes on immature viruses are first assembled as trimeric spikes in the neutral pH environment of the endoplasmic reticulum. When the virus is transported to the low pH environment of the exosomes, these spikes rearrange into dimeric structures, which lie parallel to the virus lipid envelope. The proteins involved in driving this process are unknown. Previous cryoelectron microscopy studies of the mature DENV showed that the prM-stem region (residues 111–131) is membrane-associated and may interact with the E proteins. Here we investigated the prM-stem region in modulating the virus maturation process. The binding of the prM-stem region to the E protein was shown to increase significantly at low pH compared with neutral pH in ELISAs and surface plasmon resonance studies. In addition, the affinity of the prM-stem region for the liposome, as measured by fluorescence correlation spectroscopy, was also increased when pH is lowered. These results suggest that the prM-stem region forms a tight association with the virus membrane and attracts the associated E protein in the low pH environment of exosomes. This will lead to the surface protein rearrangement observed during maturation.     

Plasma concentrations of endothelin in patients with abnormal vascular reactivity. Effects of ergometric exercise and acute saline loading

We measured circulating concentrations of endothelin, a recently discovered vasoconstrictor peptide produced by vascular endothelial cells, in healthy subjects and in patients with abnormal vascular reactivity. Endothelin concentrations were determined by radio-immunoassay after extraction of plasma using Sep-Pak C-18 cartridges in healthy subjects (n = 20), in patients with diabetes mellitus type I (n = 10), in patients with mild to moderate essential hypertension (n = 12) and in non-dialyzed patients with stable chronic renal failure (n = 12). Plasma concentrations were similar in healthy controls, in diabetics and in hypertensive patients averaging 5.0 +/- 0.6 pg/ml, 4.7 +/- 0.2 pg/ml and 6.5 +/- 1.0 pg/ml, respectively. In contrast, plasma concentrations of endothelin were markedly elevated in patients with chronic renal failure averaging 16.6 +/- 2.9 pg/ml (p less than 0.005). No correlations were observed between serum creatinine concentrations ranging from 124 to 850 mumol/l or blood pressure and plasma concentrations of endothelin. Bicycle ergometric exercise in six healthy subjects and an acute modest i.v. saline load of 1,000 ml of 0.45% NaCl administered within 60 min in six patients with mild essential hypertension did not affect plasma concentrations of endothelin. Thus, it is unlikely that vascular synthesis of endothelin is related to acute physiological changes in systemic hemodynamics or to the circulatory and renal responses to acute extracellular fluid volume (ECFV) expansion. A potential role of endothelin, however, in the control of regional blood flow cannot be excluded. Elevated plasma concentrations of endothelin observed in patients with chronic renal failure require further investigations.