selection pressure
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The newly emerging SARS-CoV-2 Omicron (B.1.1.529) variant first identified in South Africa in November 2021 is characterized by an unusual number of amino acid mutations in its spike that renders existing vaccines and therapeutic monoclonal antibodies dramatically less effective. The in vivo pathogenicity, transmissibility, and fitness of this new Variant of Concerns are unknown. We investigated these virological attributes of the Omicron variant in comparison with those of the currently dominant Delta (B.1.617.2) variant in the golden Syrian hamster COVID-19 model. Omicron-infected hamsters developed significantly less body weight losses, clinical scores, respiratory tract viral burdens, cytokine/chemokine dysregulation, and tissue damages than Delta-infected hamsters. The Omicron and Delta variant were both highly transmissible (100% vs 100%) via contact transmission. Importantly, the Omicron variant consistently demonstrated about 10-20% higher transmissibility than the already-highly transmissible Delta variant in repeated non-contact transmission studies (overall: 30/36 vs 24/36, 83.3% vs 66.7%). The Delta variant displayed higher fitness advantage than the Omicron variant without selection pressure in both in vitro and in vivo competition models. However, this scenario drastically changed once immune selection pressure with neutralizing antibodies active against the Delta variant but poorly active against the Omicron variant were introduced, with the Omicron variant significantly outcompeting the Delta variant. Taken together, our findings demonstrated that while the Omicron variant is less pathogenic than the Delta variant, it is highly transmissible and can outcompete the Delta variant under immune selection pressure. Next-generation vaccines and antivirals effective against this new VOC are urgently needed.

Gut microbiomes of humans carry a complex symbiotic assemblage of microorganisms. As in all mammals, the special mode of feeding newborn infants through milk from the mammary gland enhances the opportunity for vertical transmission of elements of this microbiome. This has potential benefits, but it also brings with it some hazards for the host. We point out here that vertical transmission from both parents would allow host populations to be invaded by elements that are deleterious. In contrast, vertical transmission, when restricted to one parent, acts as a sieve preventing the spread of such elements. Because some transmission from mother to infant is unavoidable in placental mammals, uniparental transmission of symbionts, if it were to be selected, would require some separation of the father from the newborn infant. This paper therefore puts forward the hypothesis that the asymmetry in roles of mother and father, together with the hazards that come with biparental transmission, generate a selection pressure against male lactation in humans, and in mammals in general.

Abstract Background RADIALIS (RAD), belongs to the MYB gene family and regulates a variety of functions including floral dorsoventral asymmetry in Antirrhinum majus and development of fruit proteins in Solanum lycopersicum. RAD genes contain an SNF2_N superfamily domain. Here, we comprehensively identified 68 RAD genes from six different species including Arabidopsis and five species of cotton. Results Phylogenetic analysis classified RAD genes into five groups. Gene structure, protein motifs and conserved amino acid residues indicated that GhRAD genes were highly conserved during the evolutionary process. Chromosomal location information showed that GhRAD genes were distributed unevenly on different chromosomes. Collinearity and selection pressure analysis indicated RAD gene family expansion in G. hirsutum and G. barbadense with purifying selection pressure. Further, various growth and stress related promotor cis-acting elements were observed. Tissue specific expression level indicated that most GhRAD genes were highly expressed in roots and flowers (GhRAD2, GhRAD3, GhRAD4 and GhRAD11). Next, GhRAD genes were regulated by phytohormonal stresses (JA, BL and IAA). Moreover, Ghi-miRN1496, Ghi-miR1440, Ghi-miR2111b, Ghi-miR2950a, Ghi-miR390a, Ghi-miR390b and Ghi-miR7495 were the miRNAs targeting most of GhRAD genes. Conclusions Our study revealed that RAD genes are evolutionary conserved and might be involved in different developmental processes and hormonal stress response. Data presented in our study could be used as the basis for future studies of RAD genes in cotton.

Two functional protein sequences can sometimes be separated by a fitness valley - a series of low or non-functional intermediate mutations that must be traversed to reach a more optimal or refined function. Time-varying selection pressure modulates evolutionary sampling of such valleys. Yet, how the amplitude and frequency of fluctuating selection influence the rate of protein evolution is poorly understood. Here, we derive a simple equation for the time-dependent probability of crossing a fitness valley as a function of evolutionary parameters: valley width, protein size, mutation rate, and selection pressure. The equation predicts that, under low selection pressure, the valley crossing rate is magnified by a factor that depends exponentially on valley width. However, after a characteristic time set by the evolutionary parameters, the rate rapidly decays. Thus, there is an optimal frequency of selection-pressure fluctuations that maximizes the rate of protein optimization. This result is reminiscent of the resonance frequency in mechanical systems. The equation unites empirical and theoretical results that were previously disconnected, and is consistent with time-dependent in vitro and clinical data. More generally, these results suggest that seasonal and climate oscillations could synchronously drive protein evolution at the resonant frequency across a range of organism hosts and timescales. This theory could also be applied to optimize de novo protein evolution in laboratory directed evolution using time-varying protocols.

The classical evolutionary theories of aging suggest that aging evolves due to insufficient selective pressure against it. In these theories, declining selection pressure with age leads to aging through genes or resource allocations, implying that aging could potentially be stalled were genes, resource allocation, or selection pressure somewhat different. While these classical evolutionary theories are undeniably part of a description of the evolution of aging, they do not explain the diversity of aging patterns, and they do not constitute the only possible evolutionary explanation. Without denying selection pressure a role in the evolution of aging, we argue that the origin and diversity of aging should also be sought in the nature and evolution of organisms that are, from their very physiological make up, unmaintainable. Drawing on advances in developmental biology, genetics, biochemistry, and complex systems theory since the classical theories emerged, we propose a fresh evolutionary-mechanistic theory of aging, the Danaid theory. We argue that, in complex forms of life like humans, various restrictions on maintenance and repair may be inherent, and we show how such restrictions are laid out during development. We further argue that there is systematic variation in these constraints across taxa, and that this is a crucial factor determining variation in aging and lifespan across the tree of life. Accordingly, the core challenge for the field going forward is to map and understand the mosaic of constraints, trade-offs, chance events, and selective pressures that shape aging in diverse ways across diverse taxa.

Coccidiosis is the costliest disease in the rabbit industry. The kits do not obtain maternal immunity against the diseases and therefore suckling to weaning period being the riskiest time of infection. To date, control of coccidiosis is relied on the use of chemical coccidiostat as a drug or as the substance in feed. Whilst, continuous exposure to antibiotics develops resistance and contamination in the carcass. There is no commercially provided vaccine to prevent rabbit coccidiosis cases. In this report, we processed precocious lines from the strain of Yogyakarta origin by using selection pressure to attenuate Eimeria spp. The vaccine candidate composed of 50% of each Eimeria media and Eimeria intestinalis were given orally to initiate protective immunity against rabbit coccidiosis. The vaccinated groups with 5 x 102 oocyst dosage exhibited 95% less total oocyst excretion compared to the non-vaccinated group. Our experiment showed no mortality and without any significantly detrimental response of vaccinated rabbits during the observation time (P<0.0001). Since the oocysts in the vaccinated rabbits are excreted in dropped faecal samples, it provides recirculation and provokes a group immunity within the flock. A vaccine candidate is a promising tool as a more environmentally friendly strategy for sustainable rabbit production.

The genome of the metal resistant, hydrogen-oxidizing bacterium Cupriavidus metallidurans strain CH34 contains horizontally acquired plasmids and genomic islands. Metal-resistance determinants on the two plasmids may exert genetic dominance over other related determinants. To investigate whether these recessive determinants can be activated in the absence of the dominant ones, the transcriptome of the highly zinc-sensitive deletion mutant Δe4 (Δ cadA ΔzntA ΔdmeF ΔfieF ) of the plasmid-free parent AE104 was characterized using gene arrays. As a consequence of some unexpected results, close examination by PCR and genomic re-resequencing of strains CH34, AE104, Δe4 and others revealed that the genomic islands CMGIs 2, 3, 4, D, E, but no other islands or recessive determinants, were deleted in some of these strains. Provided CH34 wild type was kept under alternating zinc and nickel selection pressure, no comparable deletions occurred. All current data suggest that genes were actually deleted and were not, as previously surmised, simply absent from the respective strain. As a consequence, a cured database was compiled from the newly generated and previously published gene array data. Analysis of data from this database indicated that some genes of recessive, no longer needed determinants were nevertheless expressed and up-regulated. Their products may interact with those of the dominant determinants to mediate a mosaic phenotype. The ability to contribute to such a mosaic phenotype may prevent deletion of the recessive determinant. The data suggest that the bacterium actively modifies its genome to deal with metal stress and the same time ensures metal homeostasis. Significance In their natural environment, bacteria continually acquire genes by horizontal gene transfer and newly acquired determinants may become dominant over related ones already present in the host genome. When a bacterium is taken into laboratory culture, it is isolated from the horizontal gene transfer network. It can no longer gain genes, but instead may lose them. This was indeed observed in Cupriavidus metallidurans for loss key metal-resistance determinants when no selection pressure was continuously kept. However, some recessive metal-resistance determinants were maintained in the genome. It is proposed that they might contribute some accessory genes to related dominant resistance determinants, for instance periplasmic metal-binding proteins or two-component regulatory systems. Alternatively, they may only remain in the genome because their DNA serves as a scaffold for the nucleoid. Using C. metallidurans as an example, this study sheds light on the fate and function of horizontally acquired genes in bacteria.

Background: The study of regressive evolution has yielded a wealth of examples where the underlying genes bear molecular signatures of trait degradation, such as pseudogenization or deletion. Typically, it appears that such disrupted genes are limited to the function of the regressed trait, whereas pleiotropic genes tend to be maintained by natural selection to support their myriad purposes. One such set of pleiotropic genes is involved in the synthesis (AANAT, ASMT) and signaling (MTNR1A, MTNR1B) of melatonin, a hormone secreted by the vertebrate pineal gland. Melatonin provides a signal of environmental darkness, thereby influencing the circadian and circannual rhythmicity of numerous physiological traits. Therefore, the complete loss of a pineal gland and the underlying melatonin pathway genes seems likely to be maladaptive, unless compensated by extrapineal sources of melatonin. Methods: We examined AANAT, ASMT, MTNR1A and MTNR1B in 123 vertebrate species, including pineal-less placental mammals and crocodylians. We searched for inactivating mutations and modelled selective pressures (dN/dS) to test whether the genes remain functionally intact. Results: We report that crocodylians retain intact melatonin genes and express AANAT and ASMT in their eyes, whereas all four genes have been repeatedly inactivated in the pineal-less xenarthrans, pangolins, sirenians, and whales. Furthermore, colugos have lost these genes, and several lineages of subterranean mammals have partial melatonin pathway dysfunction. These results are supported by the presence of shared inactivating mutations across clades and analyses of selection pressure based on the ratio of non-synonymous to synonymous substitutions (dN/dS), suggesting extended periods of relaxed selection on these genes. Conclusions: The losses of melatonin synthesis and signaling date to tens of millions of years ago in several lineages of placental mammals, raising questions about the evolutionary resilience of pleiotropic genes, and the causes and consequences of losing melatonin pathways in these species.