Natural selection onTMPRSS6associated with the blunted erythropoiesis and improved blood viscosity in Tibetan Pigs

Tibetan pigs, indigenous to Tibetan plateau, are well adapted to hypoxia. So far, there have been not any definitively described genes and functional sites responsible for hypoxia adaptation for the Tibetan pig. Here we conducted resequencing of the nearly entire genomic region (40.1 kb) of the candidate geneTMPRSS6(Transmembrane protease, serine 6) associated with hemoglobin concentration (HGB) and red blood cell count (RBC) in 40 domestic pigs and 40 wild boars from five altitudes along the Tea-horse ancient road and identified 708 SNPs, in addition to an indel (CGTG/----) in the intron 10. Both the CGTG deletion frequency and the pairwise r2linkage disequilibrium showed an increase with elevated altitudes in 838 domestic pigs from five altitudes, suggesting thatTMPRSS6has been under Darwinian positive selection. As the conserved core sequence of hypoxia-response elements (HREs), the deletion of CGTG in Tibetan pigs decreased the expression levels ofTMPRSS6mRNA and protein in the liver revealed by real-time quantitative PCR and western blot, respectively. To explore whether reducedTMPRSS6expression level could improve blood viscosity, the relationship between CGTG indel and hematologic and hemorheologic parameters in 482 domestic pigs from continuous altitudes was detected and dissected a genetic effect on reducing HGB by 13.25g/L in Gongbo’gyamda Tibetan pigs and decreasing MCV by 4.79 fl in Diqing Tibetan pigs. In conclusion, the CGTG deletion ofTMPRSS6resulted in lower HGB and smaller MCV, thereby blunting erythropoiesis and improving blood viscosity as well as erythrocyte deformability.

Molecular Adaptation of Modern Human Populations

Modern humans have gone through varied processes of genetic adaptations when their ancestors left Africa about 100,000 years ago. The environmental stresses and the social transitions (e.g., emergence of the Neolithic culture) have been acting as the major selective forces reshaping the genetic make-up of human populations. Genetic adaptations have occurred in many aspects of human life, including the adaptation to cold climate and high-altitude hypoxia, the improved ability of defending infectious diseases, and the polished strategy of utilizing new diet with the advent of agriculture. At the same time, the adaptations once developed during evolution may sometimes generate deleterious effects (e.g., susceptibility to diseases) when facing new environmental and social changes. The molecular (especially the genome-wide screening of genetic variations) studies in recent years have detected many genetic variants that show signals of Darwinian positive selection in modern human populations, which will not only provide a better understanding of human evolutionary history, but also help dissecting the genetic basis of human complex diseases.

Characterization of a T7-Like Lytic Bacteriophage (φSG-JL2) of Salmonella enterica Serovar Gallinarum Biovar Gallinarum

ABSTRACT φSG-JL2 is a newly discovered lytic bacteriophage infecting Salmonella enterica serovar Gallinarum biovar Gallinarum but is nonlytic to a rough vaccine strain of serovar Gallinarum biovar Gallinarum (SG-9R), S. enterica serovar Enteritidis, S. enterica serovar Typhimurium, and S. enterica serovar Gallinarum biovar Pullorum. The φSG-JL2 genome is 38,815 bp in length (GC content, 50.9%; 230-bp-long direct terminal repeats), and 55 putative genes may be transcribed from the same strand. Functions were assigned to 30 genes based on high amino acid similarity to known proteins. Most of the expected proteins except tail fiber (31.9%) and the overall organization of the genomes were similar to those of yersiniophage φYeO3-12. φSG-JL2 could be classified as a new T7-like virus and represents the first serovar Gallinarum biovar Gallinarum phage genome to be sequenced. On the basis of intraspecific ratios of nonsynonymous to synonymous nucleotide changes (Pi[a]/Pi[s]), gene 2 encoding the host RNA polymerase inhibitor displayed Darwinian positive selection. Pretreatment of chickens with φSG-JL2 before intratracheal challenge with wild-type serovar Gallinarum biovar Gallinarum protected most birds from fowl typhoid. Therefore, φSG-JL2 may be useful for the differentiation of serovar Gallinarum biovar Gallinarum from other Salmonella serotypes, prophylactic application in fowl typhoid control, and understanding of the vertical evolution of T7-like viruses.