Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted some time this week.
In the early, online edition of the Proceedings of the National Academy of Sciences, a Harvard University-led team describes transcriptional variability in so-called CD4+ FOXP3+ regulatory T (Treg) immune cells. Through array-based expression profiling of Treg cells and other CD4+ cells from 168 individuals with or without type 1 or type 2 diabetes, the researchers detected expression signatures that appear to be associated with type 1 diabetes, amongst other forms of Treg variability. The analysis also unearthed 110 variants that seem to act as expression quantitative trait loci in the Treg cells. "We suggest that the 'state' of [a] Treg population, as reflected by its [messenger RNA] expression profile, incorporates some genetic elements but also many non-genetic ones: parentally transmitted epigenetic traits, epigenetic remodeling during development, microbiome influence, and immunologic history," the authors conclude. "It is this integration that may define the susceptibility of a given individual to autoimmune disease."
Inbreeding leads to declines in heterozygosity and fitness that are detectable by genome-wide measures, another PNAS study suggests. The researchers genotyped three-dozen oilfield mice at more than 13,000 sites across the genome using restriction site-associated sequencing — an analysis that turned up evidence of inbreeding-related impacts on heterozygosity and fitness. Heterozygosity fitness correlations, or HFCs, also occurred in wild harbor seal populations, where the team saw ties between heterozygosity and propensity for infection by lungworm parasites. The results "arguably provide the strongest evidence to date of HFC being due to inbreeding depression in a natural population lacking a pedigree," the study's authors say. "They also suggest that under some circumstances heterozygosity may explain far more variation in fitness than previously envisaged."
Researchers from China and the US argue that RNA editing effects on protein-coding transcripts are typically non-adaptive in human cells. Instead, they found that much of this editing appears to occur by happenstance due to promiscuous RNA editing enzyme binding. The research duo did a comparative genomic analysis of information from half a dozen genomic datasets, considering almost 1,800 A-to-G RNA editing sites in human coding transcripts. Results from the analysis indicated that non-synonymous RNA edits are often deleterious and weeded out (particularly in key genes), rather than routinely serving as a source of new adaptation. GenomeWeb Daily News has more on the study, here.