Inteins are genetic parasites

Gene invasion in distant eukaryotic lineages: discovery of mutually exclusive genetic elements reveals marine biodiversity
The ISME Journal (2013) 7, 1764–1774
Adam Monier, et al.
Inteins are rare, translated genetic parasites mainly found in bacteria and archaea, while spliceosomal introns are distinctly eukaryotic features abundant in most nuclear genomes.
Using targeted metagenomics, we discovered an intein in an Atlantic population of the photosynthetic eukaryote, Bathycoccus, harbored by the essential spliceosomal protein PRP8 (processing factor 8 protein).  …
We hypothesize that intein propagation is facilitated by marine viruses; and, while intron gain is still poorly understood, presence of a spliceosomal intron where a locus lacks an intein raises the possibility of new, intein-primed mechanisms for intron gain.

Keywords: invasive elements; inteins; polymorphic introns; horizontal transfer; metagenomics; viridiplantae

The origins and distributions of introns and inteins remain one of the greatest mysteries of molecular and evolutionary biology.
Spliceosomal introns are distinctly eukaryotic features abundant in almost all nuclear genomes.
These non-coding elements interrupt coding regions (exons) of genes and are excised from the nascent mRNA prior to translation.
In contrast, inteins (internal protein) are much rarer genetic elements found in protein-coding genes from all three domains of life and viruses.
These in-frame intervening sequences are in coding regions of genes and are translated as part of the host protein. After self-catalyzed excision by the intein, the host protein flanking regions known as exteins (external protein) are ligated by a peptide bond. This intein-mediated process has been dubbed protein-splicing and maintains host protein functional integrity.

De novo mutations: 74 SNVs per genome

Current estimates of the average mutation frequencies for the different types of de novo genomic variation observed per generation per genome.

De novo mutations in human genetic disease
Nature Reviews Genetics 13, 565-575 (August 2012)
Joris A. Veltman, et al.

New mutations have long been known to cause genetic disease, but their true contribution to the disease burden can only now be determined using family-based whole-genome or whole-exome sequencing approaches.

In this Review we discuss recent findings suggesting that de novo mutations play a prominent part in rare and common forms of neurodevelopmental diseases, including intellectual disability, autism and schizophrenia.
De novo mutations provide a mechanism by which early-onset reproductively lethal diseases remain frequent in the population.
These mutations, although individually rare, may capture a significant part of the heritability for complex genetic diseases that is not detectable by genome-wide association studies.

Pathological pain and the neuroimmune interface

Pathological pain and the neuroimmune interface
Peter M. Grace, et al.
Nature Reviews Immunology  14, 217–231 (2014)

Reciprocal signalling between immunocompetent cells in the central nervous system (CNS) has emerged as a key phenomenon underpinning pathological and chronic pain mechanisms.
Neuronal excitability can be powerfully enhanced both by classical neurotransmitters derived from neurons, and by immune mediators released from CNS-resident microglia and astrocytes, and from infiltrating cells such as T cells.

In this Review, we discuss the current understanding of the contribution of central immune mechanisms to pathological pain, and how the heterogeneous immune functions of different cells in the CNS could be harnessed to develop new therapeutics for pain control.

Given the prevalence of chronic pain and the incomplete efficacy of current drugs — which focus on suppressing aberrant neuronal activity — new strategies to manipulate neuroimmune pain transmission hold considerable promise.

GWAS explains only a small proportion of the total heritability

By exploiting allied phenotypic data, it is possible to examine the genetic contribution to such aspects of disease biology (including prognosis) by comparing the genetic profiles of patients with contrasting clinical phenotypes—a so-called ‘within-cases’ analysis.

Prognosis in autoimmune and infectious disease: new insights from genetics
Clinical & Translational Immunology (2014) 3, e15
James C Lee, et al.

Keywords: autoimmunity; FOXO3; genetics; infection; prognosis

despite the apparent success, GWAS results have only explained a relatively small proportion of the total heritability of each disease.[3]
Work is now underway to try to identify the ‘missing heritability’ through a variety of complementary methods, including:

  • whole-genome sequencing (to identify rare variants that may have larger effect sizes) and
  • studies to examine interactions between a given gene and other genes (epistasis) and
  • between genes and the environment.


Are vitamins good for you?

Nutrition: Vitamins on trial
After decades of study, researchers still can’t agree on whether nutritional supplements actually improve health.
Melinda Wenner Moyer
Nature 510, 462–464 (26 June 2014)

But scientific opinion about the use of vitamin supplements by millions of seemingly healthy people has never been more divided.

“The tools we’ve had in the past have been so crude — it’s like we’ve been looking through a dirty window with the curtains closed,”

one of the many complexities of nutrient metabolism.
Nutrition scientists now recognize that risk curves are J- or U-shaped: nutrients have beneficial effects at low doses and toxic effects at high doses.
The magnitude of the response differs, too, depending on where individuals start on the curve — their baseline status.

Are supplements useless?
The current state of research offers only an equivocal half-answer: ‘maybe yes’ for some individuals, nutrients and doses, and ‘maybe no’ for others.
“Nutrition is complex, and I don’t think we’re necessarily going to find one formula that works for everybody,” says Mayne.

related article on within-cases analysis:

Retraction: STAP papers

The STAP papers have been retracted (July 2, 2014), but the original Nature publications are not yet labeled as such:

Stimulus-triggered fate conversion of somatic cells into pluripotency
Nature  505, 641–647 (30 January 2014)
Haruko Obokata, et al.

Here we report a unique cellular reprogramming phenomenon, called stimulus-triggered acquisition of pluripotency (STAP), which requires neither nuclear transfer nor the introduction of transcription factors.
In STAP, strong external stimuli such as a transient low-pH stressor reprogrammed mammalian somatic cells, resulting in the generation of pluripotent cells.
Through real-time imaging of STAP cells derived from purified lymphocytes, as well as gene rearrangement analysis, we found that committed somatic cells give rise to STAP cells by reprogramming rather than selection.
STAP cells showed a substantial decrease in DNA methylation in the regulatory regions of pluripotency marker genes.

Blastocyst injection showed that STAP cells efficiently contribute to chimaeric embryos and to offspring via germline transmission.

We also demonstrate the derivation of robustly expandable pluripotent cell lines from STAP cells.
Thus, our findings indicate that epigenetic fate determination of mammalian cells can be markedly converted in a context-dependent manner by strong environmental cues.