Genes that cause heart disease have benefits! (or at least are selected for)

Genes that cause heart disease have benefits! (or at least are selected for)

Byars SG, Huang QQ, Gray L-A, Bakshi A, Ripatti S, Abraham G, et al. (2017) Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy. PLoS Genet 13(6): e1006328. https://doi.org/10.1371/journal.pgen.1006328  (Open access)

Author summary: How genetic variation contributes to disease is complex, especially for those such as coronary artery disease (CAD) that develop over the lifetime of individuals. One of the fundamental questions about CAD––whose progression begins in young adults with arterial plaque accumulation leading to life-threatening outcomes later in life––is why natural selection has not removed or reduced this costly disease. It is the leading cause of death worldwide and has been present in human populations for thousands of years, implying considerable pressures that natural selection should have operated on. Our study provides new evidence that genes underlying CAD have recently been modified by natural selection and that these same genes uniquely and extensively contribute to human reproduction, which suggests that natural selection may have maintained genetic variation contributing to CAD because of its beneficial effects on fitness. This study provides novel evidence that CAD has been maintained in modern humans as a by-product of the fitness advantages those genes provide early in human lifecycles.

 

Special Discount for ISEMPH meeting registration by June 30

Special Discount for ISEMPH meeting registration by June 30

An 80 Euro discount on meeting registration fees is available to readers of the EvMedReview who register by June 30 and use the code “ISEMPHFRIENDS” at checkout.

The 2017 IEMPH Meeting in Groningen, Netherlands, August 18-21 offers rare opportunity to hear great talks by the leaders in evolutionary medicine and have conversations with many who share common interests, including members of the European Society for Evolutionary Biology, that is holding its meeting in conjunction with ISEMPH.12 medical Accreditation credits are provided for meeting participants. 

Another bonus: Those attending either ESEB or ISEMPH are also eligible to submit a paper to Evolution, Medicine & Public Health without paying the usual $2000 author’s fees. Details here.

The full program for the ISEMPH meeting is posted here.

Please share this offer with friends, colleagues… and your doctor!

 

 

Evolution of the Human Immune Response

Evolution of the Human Immune Response

Living in an adaptive world: Genomic dissection of the genus Homo and its immune response
A Review Article by Hélène Quach and Lluis Quintana-Murci

in  The Journal of Experimental Medicine 214:877-894 (2017)
Doi.org/10.1084/jem.20161942 (open access)

Commentary by Jon Laman

Two authors from Paris, France, provide a wonderfully concise and sophisticated overview on how evolution shaped our current immune response. Their review is a scientific and educational treasure trove, written in accessible form, and with 6 very instructive figures, box and table. For those from other fields, it is useful to point out that the Journal of Experimental Medicine is highly read and respected in the fields of hematology, immunology, and regenerative medicine. Hence, this article has high visibility bringing these evolutionary aspects to a large audience.

While discussing classic and recent exciting primary studies, this review also refreshes many basics (e.g. human migration across the globe in Figure 1, in its 2017 guise), and explains important concepts not always widely known (e.g. archaic introgression of Neanderthal sequences; regulatory variants of gene expression eQTL versus protein quantitative trait loci – pQTL).

Their Table 1, Some iconic cases of positive selection in the human genome will find its way to slides in many presentations.

It is worthwhile that in addition to the strong emphasis on genetics driving quality and intensity of the immune response, the authors state on page 887 that “a large fraction of the variation in immune responses cannot be attributed to genetic factors”. They cite papers demonstrating roles of age and gender, annual seasonality, social environment, and gut microbiota composition.

In the last section the authors emphasize the role of environmental and cultural factors promoting transmission of advantageous or negative immune traits across generations, such as access to medical care, smoking, diet, and mate choice.

This concise review is also an excellent teaching resource. For instance, together with a review on evolutionary molecular medicine (Nesse, Ganten, Gregory and Omenn, 2012) and a glossary of evolutionary terms (INSERT LINK TO MY PDF HERE), a very doable starter package can be compiled for (medical) students as well as for more advanced audiences.

Instant classroom-flipping assignments are to have participants present 1-4 slide Powerpoints of five minutes to explain to peers the items covered in the figures of this review. For instance Figure 3, Natural selection and archaic introgression affect human genome diversity, provides good level conceptual and technical challenges for student didactic skills.

In conclusion, the two authors are to be highly commended on this useful paper. One would hope to see updates regularly of the same high quality, in view of the rapid advances in this field.

 

Jon Laman
Prof. Dr. Jon D. Laman
Professor of Immune Physiology
Head Department of Neuroscience
University Medical Center Groningen
PO Box 196, 9700 AD Groningen, The Netherlands
e-mail  j.d.laman@umcg.nl
website http://neuroscience.umcg.nl

Additional (teaching) materials;
Evolutionary molecular medicine.

Nesse RM, Ganten D, Gregory TR, Omenn GS.
J Mol Med (Berl). 2012, 90:509-22. doi: 10.1007/s00109-012-0889-9. Review.

Jon Laman Glossary of evolutionary terms 2017
(A pdf valuable for teaching and learning.) 

ISEMPH and ESEB Meeting Registrants can submit to EMPH with no author’s fees

ISEMPH and ESEB Meeting Registrants can submit to EMPH with no author’s fees

A Special offer from Evolution, Medicine, and Public Health and Oxford University Press 

In honor of the 2017 meeting of the International Society of Evolution, Medicine, & Public Health and the 2017 Congress of the European Society for Evolutionary Biology, Oxford University Press is pleased to extend a special offer to all ISEMPH and ESEB attendees.

For a limited time only, we are waiving author fees for research submitted to ISEMPH’s open access flagship journal Evolution, Medicine, and Public Health.
Submit an article to the journal as corresponding author during August or September 2017 and take advantage of free publication.

MORE ABOUT EMPH:
Evolution, Medicine, and Public Health is an open access journal that publishes original, rigorous applications of evolutionary science to issues in medicine and public health. It aims to connect evolutionary biology with the health sciences to produce insights that may reduce suffering and save lives.

  • Fast first decision and rapid publication times
  • High-quality and constructive peer review
  • Discoverable in PubMed and deposited in PMC
  • Compliant with NIH, HHMI, Wellcome and RCUK public access policies
  • Automatic consideration for the annual $5,000 George C. Williams Prize, awarded to the author of the most significant article published in the preceding year

Browse the journal’s Information for Authors or submit your research now.

DID YOU KNOW?
Members of the International Society for Evolution, Medicine, & Public Health receive a $1000 discount on publication fees for articles published in EMPH. Become an ISEMPH member and benefit from deeply discounted rates at any time!

Prebiotics cut down body fat in obese children

Prebiotics cut down body fat in obese children

This post is the third of a recent trilogy on links between the microbiome and health. Researchers from the University of Calgary have carried out a trial on 7 to 12 year old children who were classified as overweight or obese for their age. Although the total number of children in the trial was fairly small – 42 individuals – the trial was double-blinded and placebo controlled. The children were assigned into groups which were either given a readily available prebiotic fibrous product, oligofructose-enriched inulin, or a placebo, for 16 weeks. The experiment is reported in an open access uncorrected proof in the journal Gastroenterology.

Over the 16 weeks, the researchers measured fat mass and lean mass; height, weight and waist circumference; and analysed blood samples for lipids, cytokines, lipopolysaccharide, and insulin. They also took stool samples to check for changes to the resident gut microbiota. They noted changes between the prebiotic-treated group and the controls at a number of levels. There was a decrease in serum triglycerides of 19% in the prebiotic group, while there were significant increases in species of Bifidobacterium – a direct result of filling the gut with fiber – and decreases in Bacteroides vulgatus. The prebiotic treatment palpably slowed weight gain: the placebo group recorded a 2.4 fold increase in body weight over the prebiotic group over 16 weeks and while the prebiotic group held Body Mass Index stable over this period it was significantly increased in the placebo group. Percentage total body fat was also clearly lower in the prebiotic group by the end of the experimental period. While the duration of the experiment and the young age of the children meant that indicators of widespread inflammation were not noticed they did see a higher level of circulating inflammatory cytokine interleukin-6 in the placebo group and they are now planning bigger trials of this very simple dietary intervention to provide more evidence of cheap and efficient control of childhood obesity. This looks like a group of significantly overweight children rescued from two forms of evolutionary mis-match: a couch-potato life-style rich in fats and refined carbs, and an unhealthy gut microbiota incapable of regulating inflammation and adiposity.

Can the gut microbiota slow the progression of Alzheimer’s disease?

Can the gut microbiota slow the progression of Alzheimer’s disease?

In a current paper in Scientific Reports, Bonfilli et al describe research on a mouse model of Alzheimer’s disease that provides strong and detailed evidence for multiple changes in the diseased brain that appear to lead to an amelioration of neurodegeneration. The AD mice were treated with a probiotic formulation called SLAB51, rich in lactic acid bacteria and bifidobacteria, and the assumption is that the modulation of the gut microbiota this causes affects the brain and behaviour through the gut-brain axis.

On a behavioural level, treated mice out-performed controls on several tests of memory including the novel-object recognition (NOR) test which is used to evaluate recognition memory and is based on the spontaneous tendency of rodents to spend more time exploring a novel object than a familiar one. The amount of time the rodent spends exploring each novel object over a 10 minute test period provides a powerful measurement of memory integrity and attention. Treated mice also out-performed controls on a passive avoidance test which relies on memory of punishment.

In terms of brain anatomy there were notable differences in cortical thickness between probiotic treated and un-treated AD mice, particularly in the hippocampus, and ventricular enlargement in the untreated individuals. They then measured the plasma concentration of the gut peptide hormones ghrelin, leptin, GLP-1 and GIP because of their neuroprotective effects and potential as therapeutic targets and found them elevated in the treated AD mice. With respect to the main culprit in Alzheimer’s disease – ß amyloid, they noted that the load of the more toxic peptide, ß-amyloid-42, was decreased in treated mice, together with amyloid oligomers. They saw a significant reduction of extracellular amyloid deposits. They also recorded a restoration of proteolytic pathways and autophagy in the brains of probiotic-treated AD mice. In particular, they noted a strong increase in the apoptotic p53 in untreated AD mice which was held in check in treated mice. The SLAB51 probiotic was able to restore cathepsin L activity in 18- and 24-week-old mice compared with controls which was of particular interest considering the ability of this enzyme to increase α-secretase activity, thereby suppressing Aβ levels.

All in all, their results suggest a restoration of hippocampal function in probiotic treated AD mice. Improvement of cognitive function seems supported by increased plasma concentration of gut hormones such as ghrelin, leptin, GLP1 and GIP( these are lowered in AD patients which is important because there is evidence that ghrelin reduces synaptic degeneration and leptin is neuroprotective against ß-amyloid at least in vitro and directly affects the gamma-secretase amyloidogenic pathway). They showed that the probiotics counteracted the typical morphological alterations of AD, including reduction in brain weight, decline of cortical areas, and general brain damage and shrinkage. Furthermore, SLAB51 contributed to a consistent reduction in the amount of cerebral Aβ, both in the form of peptides and oligomers. Consequently, a decreased number and size of amyloid plaques were observed upon treatment. All this adds up, they say, to a convincing display of the delaying action of probiotic gut microbiota modulation on Alzheimer’s progression.