Parthenogenetic Darevskia lizards mate frequently if they have the chance: a quantitative analysis of copulation marks in a sympatric zone

Several Caucasian rock lizards of the genus Darevskia of hybrid origin are known to reproduce parthenogenetically. Local communities can be composed exclusively of parthenogens, though syntopy with bisexual members of the genus may occur. In some localities, reproduction between bisexual and parthenogenetic Darevskia has been previously reported based on lizard intermediate morphology and karyology (3n, 4n). However, the frequency of such heterospecific matings remains unknown. We indirectly quantified the reproductive interactions through the inspection of copulation marks in females in a mixed Darevskia community from Kuchak (Armenia) composed of two hybrid parthenogens (D. armeniaca and D. unisexualis), one bisexual species (D. valentini) and their putative backcrosses. A total of 139 adults were randomly collected and photographed. Females were later measured (SVL), inspected for inguinal marks and ranked from 0 (no scars) to 3 (≥ 3 scars). The lizard species and ploidy determination was ensured by a parallel microsatellite analysis. Sex-ratio in the community was extremely biased due to the high abundance of parthenogenetic females. All female types displayed copulation marks with frequencies varying from 80% in D. valentini to 64% in D. armeniaca. Remarkably, 7 out of 11 (64%) backcross females also showed marks. In the most abundant D. armeniaca, the prevalence and intensity of copulation marks increased with body size, just as predicted for polygynous female lacertids. These results indicate that copulation between parthenogenetic and bisexual species in Darevskia mixed communities is common and driven by sexual selection, thus reinforcing previous suggestions of reproductive interaction in syntopy. Evolutionary implications of these findings are discussed.     

Crystal structure of a potassium ion transporter, TrkH

The TrkH/TrkG/KtrB proteins mediate K(+) uptake in bacteria and probably evolved from simple K(+) channels by multiple gene duplications or fusions. Here we present the crystal structure of a TrkH from Vibrio parahaemolyticus. TrkH is a homodimer, and each protomer contains an ion permeation pathway. A selectivity filter, similar in architecture to those of K(+) channels but significantly shorter, is lined by backbone and side-chain oxygen atoms. Functional studies showed that TrkH is selective for permeation of K(+) and Rb(+) over smaller ions such as Na(+) or Li(+). Immediately intracellular to the selectivity filter are an intramembrane loop and an arginine residue, both highly conserved, which constrict the permeation pathway. Substituting the arginine with an alanine significantly increases the rate of K(+) flux. These results reveal the molecular basis of K(+) selectivity and suggest a novel gating mechanism for this large and important family of membrane transport proteins.     

Crystal structure of a phosphorylation-coupled saccharide transporter

Saccharides have a central role in the nutrition of all living organisms. Whereas several saccharide uptake systems are shared between the different phylogenetic kingdoms, the phosphoenolpyruvate-dependent phosphotransferase system exists almost exclusively in bacteria. This multi-component system includes an integral membrane protein EIIC that transports saccharides and assists in their phosphorylation. Here we present the crystal structure of an EIIC from Bacillus cereus that transports diacetylchitobiose. The EIIC is a homodimer, with an expansive interface formed between the amino-terminal halves of the two protomers. The carboxy-terminal half of each protomer has a large binding pocket that contains a diacetylchitobiose, which is occluded from both sides of the membrane with its site of phosphorylation near the conserved His250 and Glu334 residues. The structure shows the architecture of this important class of transporters, identifies the determinants of substrate binding and phosphorylation, and provides a framework for understanding the mechanism of sugar translocation.     

Functional genomics reveal that the serine synthesis pathway is essential in breast cancer

Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.     

Retroelements and their impact on genome evolution and functioning

Retroelements comprise a considerable fraction of eukaryotic genomes. Since their initial discovery by Barbara McClintock in maize DNA, retroelements have been found in genomes of almost all organisms. First considered as a “junk DNA” or genomic parasites, they were shown to influence genome functioning and to promote genetic innovations. For this reason, they were suggested as an important creative force in the genome evolution and adaptation of an organism to altered environmental conditions. In this review, we summarize the up-to-date knowledge of different ways of retroelement involvement in structural and functional evolution of genes and genomes, as well as the mechanisms generated by cells to control their retrotransposition.