G. (2011). Rethinking the evolution of extant subSaharan African suids (Suidae, Artiodactyla). -Zoologica Scripta, 40, 327-335. Although African suids have been of scientific interest for over two centuries, their origin, evolution, phylogeography and phylogenetic relationships remain contentious. There has been a longrunning debate concerning the evolution of pigs and hogs (Suidae), particularly regarding the phylogenetic relationships among extant Eurasian and African species of the subfamily Suinae. To investigate these issues, we analysed the mitochondrial and nuclear DNA sequences of extant genera of Suidae from Eurasia and Africa. Molecular phylogenetic analyses revealed that all extant sub-Saharan African genera form a monophyletic clade separate from Eurasian suid genera, contradicting previous attempts to resolve the Suidae phylogeny. Two major sub-Saharan African clades were identified, with Hylochoerus and Phacochoerus grouping together as a sister clade to Potamochoerus. In addition, we find that the ancestors of extant African suids may have evolved separately from the ancestors of modern day Sus and Porcula in Eurasia before they colonised Africa. Our results provide a revision of the intergeneric relationships within the family Suidae.

African swine fever virus (ASFV) is a highly infectious disease of domestic pigs, with virulent isolates causing a rapidly fatal hemorrhagic fever. In contrast, the porcine species endogenous to Africa tolerate infection. The ability of the virus to persist in one host while killing another genetically related host implies that disease severity may be, in part, modulated by host genetic variation. To complement transcription profiling approaches to identify the underlying genetic variation in the host response to ASFV, we have taken a candidate gene approach based on known signaling pathways that interact with the virus-encoded immunomodulatory protein A238L. We report the sequencing of these genes from different pig species and the identification and initial in vitro characterization of polymorphic variation in RELA (p65; v-rel reticuloendotheliosis viral oncogene homolog A), the major component of the NF-B transcription factor. Warthog RELA and domestic pig RELA differ at three amino acids. Transient cell transfection assays indicate that this variation is reflected in reduced NF-B activity in vitro for warthog RELA but not for domestic pig RELA. Induction assays indicate that warthog RELA and domestic pig RELA are elevated essentially to the same extent. Finally, mutational studies indicate that the S531P site conveys the majority of the functional variation between warthog RELA and domestic pig RELA. We propose that the variation in RELA identified between the warthog and domestic pig has the potential to underlie the difference between tolerance and rapid death upon ASFV infection.

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A hallmark of acute promyelocytic leukemia (APL) is altered nuclear architecture, with disruption of promyelocytic leukemia (PML) nuclear bodies (NBs) mediated by the PML-retinoic acid receptor α (RARα) oncoprotein. To address whether this phenomenon plays a role in disease pathogenesis, we generated a knock-in mouse model with NB disruption mediated by 2 point mutations (C62A/C65A) in the Pml RING domain. Although no leukemias developed in Pml mice, these transgenic mice also expressing RARα linked to a dimerization domain (p50-RARα model) exhibited a doubling in the rate of leukemia, with a reduced latency period. Additionally, we found that response to targeted therapy with all- retinoic acid in vivo was dependent on NB integrity. PML-RARα is recognized to be insufficient for development of APL, requiring acquisition of cooperating mutations. We therefore investigated whether NB disruption might be mutagenic. Compared with wild-type cells, primary Pml cells exhibited increased sister-chromatid exchange and chromosome abnormalities. Moreover, functional assays showed impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ) repair pathways, with defective localization of Brca1 and Rad51 to sites of DNA damage. These data directly demonstrate that Pml NBs are critical for DNA damage responses, and suggest that Pml NB disruption is a central contributor to APL pathogenesis.