By using whole-exome sequencing on a family with two children affected by a rare, severe skeletal dysplasia, investigators at Australia's University of Queensland "identified two novel compound heterozygous loss-of-function mutations in POP1, which encodes a core component of the RNase mitochondrial RNA processing complex that directly interacts with the RMRP RNA domains that are affected in anauxetic dysplasia." These POP1 mutations, as the authors report in PLoS Genetics this week, impair both the "integrity and activity" of the RNase mitochondrial RNA processing complex as well as cell proliferation, "providing likely molecular and cellular mechanisms" through which this severe skeletal dysplasia occurs.
Researchers at Uppsala University in Sweden and elsewhere report on their use of ultra-deep sequencing on mtDNA mutator mice. They "found no increase in levels of point mutations or deletions in wild-type C57Bl/6N mice with increasing age, thus questioning the causative role of these changes in aging." In its PLoS Genetics paper, the team also shows that "most somatic mtDNA mutations occur as replication errors during development," rather than as a result of oxidative damage during adult life.
Over in PLoS One, a team led by investigators at the National Institute on Drug Abuse reports on signatures of "altered gene expression in pulmonary tissues of tryptophan hydroxylase-1 knockout mice" and how these could have "implications for pulmonary arterial hypertension" in humans. By testing the two alternative hypotheses that "Tph1−/− mice express lower levels of pulmonary 5-HT transporter (SERT) when compared to wild-type controls," and that "Tph1−/− mice display adaptive changes in the expression of non-serotonergic pulmonary genes" associated with pulmonary arterial hypertension, the team found 51 genes that are "significantly altered in the lungs of female Tph1−/− mice."
And in PLoS Computational Biology this week, a trio of investigators at the National Center for Biotechnology Information and Utrecht University in the Netherlands discusses the evolutionary origin of DNA. Using minimal computational models of RNA replicator systems, the NBCI-Utrecht group shows that "RNA can function as both template-directed polymerase and template, whereas DNA can function only as template." In subsequent analyses, the group's results partially "explained ... the trade-off between template and catalyse that is inherent in RNA-only replication cycles: DNA releases RNA from this trade-off by making it unnecessary for RNA to serve as template and so rendering the system more resistant against evolving parasitism."