Ribonucleotide reductase (RNR) is an essential enzyme that catalyzes the synthesis of DNA building blocks in virtually all living cells. NrdR, an RNR-specific repressor, controls the transcription of RNR genes and, often, its own, in most bacteria and some archaea. NrdR senses the concentration of nucleotides through its ATP-cone, an evolutionarily mobile domain that also regulates the enzymatic activity of many RNRs, while a Zn-ribbon domain mediates binding to NrdR boxes upstream of and overlapping the transcription start site of RNR genes. Here, we combine biochemical and cryo-EM studies of NrdR from Streptomyces coelicolor to show, at atomic resolution, how NrdR binds to DNA. The suggested mechanism involves an initial dodecamer loaded with two ATP molecules that cannot bind to DNA. When dATP concentrations increase, an octamer forms that is loaded with one molecule each of dATP and ATP per monomer. A tetramer derived from this octamer then binds to DNA and represses transcription of RNR. In many bacteria — including well-known pathogens such as Mycobacterium tuberculosis — NrdR simultaneously controls multiple RNRs and hence DNA synthesis, making it an excellent target for novel antibiotics development.

One of the main tasks of the PROCAMED project is to promote research on genetics of dromedary camel. In this regard, and to evaluate the genetic diversity among Tunisian dromedary camel, a total of 62 blood samples were collected from unrelated animals in three different regions (Tataouine, Medenine and Kebili) and belonging to three sub-populations (Ourdhaoui Médenine, Ourdhaoui Tataouine and Merzougui) defined on the basis of morphologic and geographic criterions. From seven microsatellite markers used only four were successfully amplified resulting in a total of 26 alleles observed in the three sub-populations with a mean number of alleles (MNA) of 6.5. Unbiased expected heterozygosity (He) ranged from 0.76 to 0.84 whereas the observed heterozygosity was absolute (Ho = 1) and an excess of heterozygotes was observed in the three groups for all four loci. The mean estimates of the fixation index FST was 0.052 showing a moderate genetic structure between the different sub-populations. Little differentiation was observed between Ourdhaoui Médenine and Merzougui sub-populations, compared to Ourdhaoui Tataouine sub-population which seems to be more established. The results showed the limits of camel classification on the basis of only morphologic and regional distribution criterions.

This study analyzed the genetic variability, inbreeding and population structure of the Tunisian–North African dairy sheep breed, the Sicilo-Sarde (SS), created by crossing the Sarda and Comisana dairy breeds. The level of variability in the SS, considered as an endangered breed after a dramatic decrease, was assessed using 17 microsatellite markers by analyzing the two breed populations sampled from their respective cradles: SS of Beja (SSB, n = 27) and SS of Mateur (SSM, n = 25). High levels of genetic diversity in SS were revealed, with a total of 212 alleles, a high mean number of alleles (12.47 ± 4.17) and a high average polymorphism information content (PIC) (0.81 ± 0.10). The observed heterozygosity was considerable in SSB and SSM (0.795 and 0.785, respectively). The inbreeding level measured by the population inbreeding coefficient FIS is higher in the SSM population (0.121) than in the SSB population (0.090). The higher genetic diversity level detected in SSB reflected the effect of new Italian Sarda genes introduced by intra-uterine artificial insemination recently practiced in this population. The Wilcoxon test and the mode-shift distribution indicated that the SS breed is a non-bottlenecked population. The structural analysis reflected the historical miscegenation practiced during breed creation and highlighted further ancient miscegenation, which could date back to the introduction of the first sheep wave introduction to the western Mediterranean. Microsatellite markers were successfully applied in the assessment of the genetic variability of SS and should be used in monitoring this variability during the application of conservation strategies.

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