Gao, F. — Page 11 | bioRxiv Science

bioRxiv2018

Genome analysis of the unicellular eukaryote Euplotes vannus provides insights into mating type determination and tolerance to environmental stresses

As a model organism in studies of cell and environmental biology, the free-living and cosmopolitan ciliated protist Euplotes vannus has more than ten mating types (sexes) and shows strong resistance to environmental stresses. However, the molecular basis of its sex determination mechanism and how the cell responds to stress remain largely unknown. Here we report a combined analysis of de novo assembled high-quality macronucleus (MAC; i.e. somatic) genome and partial micronucleus (MIC; i.e. germline) genome of Euplotes vannus. Furthermore, MAC genomic and transcriptomic data from several mating types of E. vannus were investigated and gene expression levels were profiled under different environmental stresses, including nutrient scarcity, extreme temperature, salinity and the presence of free ammonia. We found that E. vannus, which possesses gene-sized nanochromosomes in its MAC, shares a similar pattern on frameshifting and stop codon usage as Euplotes octocarinatus and may be undergoing incipient sympatric speciation with Euplotes crassus. Somatic pheromone loci of E. vannus are generated from programmed DNA rearrangements of multiple germline macronuclear destined sequences (MDS) and the mating types of E. vannus are distinguished by the different combinations of pheromone loci instead of possessing mating type-specific genes. Lastly, we linked the resilience to environmental temperature change to the evolved loss of temperature stress-sensitive regulatory regions of HSP70 gene in E. vannus. Together, the genome resources generated in this study, which are available online at Euplotes vannus DB (http://evan.ciliate.org), provide new evidence for sex determination mechanism in eukaryotes and common pheromone-mediated cell-cell signaling and cross-mating.

genomics↗

bioRxiv2017

Infant Transmitted/Founder HIV-1 Viruses from Peripartum Transmission are Neutralization Resistant to Paired Maternal Plasma

Despite extensive genetic diversity of HIV-1 in chronic infection, infant HIV-1 infection involves selective transmission of a single or few maternal virus variants. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env)-specific IgG responses capable of blocking this group of viruses. However, the maternal or infant factors that contribute to selection of infant T/F viruses are not well understood. In this study, we isolated HIV-1 env genes by single genome amplification from 16 mother-infant transmitting pairs from the U.S. pre-antiretroviral era Women Infant Transmission Study (WITS). Infant T/F and representative maternal non-transmitted Env variants from plasma were identified and used to generate pseudoviruses for paired maternal plasma neutralization sensitivity analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma. Yet, all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies and variably sensitive to heterologous plasma neutralizing antibodies. Moreover, infant T/F pseudoviruses were overall more neutralization resistant compared to maternal non-transmitted plasma variants (p=0.012). Altogether, our findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the spector that enhancement of this response at the end of pregnancy could further reduce infant HIV infection risk.\n\nAuthor SummaryMother to child transmission (MTCT) of HIV-1 can occur during pregnancy (in utero), at the time of delivery (peripartum) or by breastfeeding (postpartum). With the availability of anti-retroviral therapy (ART), rate of MTCT of HIV-1 have been significantly lowered. However, significant implementation challenges remains in resource-poor areas, making it difficult to eliminate pediatric HIV. An improved understanding of the viral population (escape variants from autologous neutralizing antibodies) that lead to infection of infants at time of transmission will help in designing immune interventions to reduce vertical HIV-1 transmission. Here, we selected 16 HIV-1-infected mother-infant pairs from WITS cohort (from pre anti-retroviral era), where infants became infected peripartum. HIV-1 env gene sequences were obtained by the single genome amplification method. The sensitivity of these infant Env pseudoviruses against paired maternal plasma and a panel of broadly neutralizing monoclonal antibodies (bNAbs) was analyzed. We demonstrated that the infant T/F viruses were more resistant against maternal plasma than non-transmitted maternal variants, but sensitive to most (bNAbs). Signature sequence analysis of infant T/F and non-transmitted maternal variants revealed the potential importance of V3 and MPER region for resistance against to paired maternal plasma. These findings provide insights for the design of maternal immunization strategies to enhance neutralizing antibodies that target V3 region of autologous virus populations, which could work synergistically with maternal ARVs to further reduce the rate of peripartum HIV-1 transmission.

molecular biology↗

bioRxiv2017

Adaptation of the FADS gene family in Europe: Variation across time, geography and subsistence

Fatty acid desaturase (FADS) genes encode rate-limiting enzymes for the biosynthesis of omega-6 and omega-3 long chain polyunsaturated fatty acids (LCPUFAs). This biosynthesis is essential for individuals subsisting on LCPUFAs-poor, plant-based diets. Positive selection on FADS genes has been reported in multiple populations, but its presence and pattern in Europeans remain elusive. Here, with analyses of ancient and modern DNA, we demonstrated that positive selection acted on the same FADS variants both before and after the advent of farming in Europe, but on opposite alleles. Selection in recent farmers also varied geographically, with the strongest signal in Southern Europe. These varying selection patterns concur with anthropological evidence of differences in diets, and with the association of recently-adaptive alleles with higher FADS1 expression and enhanced LCPUFAs biosynthesis. Genome-wide association studies revealed associations of recently-adaptive alleles with not only LCPUFAs, but also other lipids and decreased risk of several inflammation-related diseases.

genomics↗