Category Archives: Genetics

All humans, and two ancestors?

Daily Mail reports a study in Human Evolution with comments at

A scientific study has prompted speculation that all modern humans could have descended from a solitary pair who lived 100,000 to 200,000 years ago.
Scientists surveyed the genetic ‘bar codes’ of five million animals – including humans – from 100,000 different species and the results have prompted speculation that we sprang from a single pair of adults after a catastrophic event almost wiped out the human race.
These bar codes, or snippets of DNA that reside outside the nuclei of living cells, suggest that it’s not just people who could have come from a single pair of beings, but nine out of every 10 animal species, too.

I have heard that before.

How does the soma to germline transfer work?

I never had problems to understand environmental induced sperm methylation as spermatozoa of animals are produced continuously by meiotic division.  But I learned that in humans all ova are produced before birth, so how could these ever be influenced by an environmental exposure? It seems that the dogma of prefabricated eggs is wrong as described already in 2012.

Rare mitotically active cells have a gene expression profile that is consistent with primitive germ cells. Once established in vitro, these cells can be expanded for months and can spontaneously generate 35- to 50-μm oocytes

So there is a lifelong chance that environmental exposures both in fathers and mothers can be transmitted to the offspring “fat eggs, fat offspring” – there is no Weismann Barrier. (This remains also an important question as somatic gegen therapy could accidentally introduced germline changes – at least in theory).

But how does any soma to germline transfer work? A new paper examined this  in more detail. They found that the negative regulator of sperm activation in C elegans, SWM-1, is produced in body wall muscle, then secreted into the body cavity. Whenever it enters the gonad it finds it target TRY-5, a spermiogenesis activator, that influences sperm success.

So to the more conventional soma to germline theories of persistent methylation changes or RNA fragments ( as described in a recent review) there maybe more possibilities like microbiome transfer.

Der chinesische Menschenversuch

Der geplante Tabubruch – eine kommentierte Presse- und Literaturschau.

Wir haben es lange gefürchtet, es wird ein verrückter Einzeltäter sein, der als erster einen genmanipulierten Menschen produzieren wird. Nature berichtet heute mittag über eine Serie von Youtube Videos, die bereits gestern am 25.11. hochgeladen wurden.

He Jiankui, a genome-editing researcher from the Southern University of Science and Technology of China in Shenzhen, says that he implanted into a woman an embryo that had been edited to disable the genetic pathway that allows a cell to be infected with HIV … The scientist’s claims have not been verified through independent genome testing or published in a peer-reviewed journal. But, if true, the birth would represent a significant — and controversial — leap in the use of genome-editing. So far these tools have only be used in embryos for research, often to investigate the benefit of using them to eliminate disease-causing mutations from the human germline. But reports of off-target effects in some studies have raised significant safety concerns.

Die Literaturliste auf der Website von Jiankui He Continue reading Der chinesische Menschenversuch

No eternal life

Seven years ago we published a 15% heritability of life span from data in South Tyrol. The heritability of longevity increased from 0.20 to 0.35 as the longevity threshold increased.

A new study now finds that we have been exaggerating

true heritability of human longevity for birth cohorts across the 1800s and early 1900s was well below 10%, and that it has been generally overestimated due to the effect of assortative mating. … Spouse life spans correlate as much or more than those of genetic relatives, raising the possibility that correlated environments and/or assortative mating have confounded those estimates.

I think there is a misunderstanding of assortative mating (AM). AM is a form of sexual selection in which individuals with similar phenotypes mate with one another more frequently than would be expected under chance conditions. BUT the phenotype longevity is not known to anyone at mating. Instead there seems to be a simple “environmental” interaction: We know that elderly couples frequently die together, also known as broken hearts phenomenon.

Adjusting any regression model for any AM will therefore seriously reduces the heritability of longevity, which is exactly what the authors describe in their new paper.

Spousal correlation is expected on two grounds: shared-household environment during adulthood and/or assortative mating. The two can be distinguished by definition: the effects of shared-household environment are nontransferable through inheritance, whereas the factors correlated by assortative mating are transferable, allowing them to also generate correlations with family members of the spouse

This is not very convincing as A) shared-household environment can be transmitted by epigenetic factors and B) it is a myth there is any AM for lifespan.

Cell life span in the human body: 7 years?

Karel & Iris Schrijver “Living with the starts” have an intestine chapter “Dying to Live” that is about the cell turn over

Take the skin, for example: a Iiving, breathing, regenerating tissue that is the largest organ of the body and that acts as a barrier between the internal organs and the environment. In adults, it encompasses about 22 square feet (2 m2) and weighs around eight pounds (4 kg). It protects the interior of the body from injury, from harmful effects of microorganisms, and from the damaging ultraviolet rays of the Sun. It plays a role in the body’s thermal regulation through the constriction or dilatation of small blood vessels, it contains nerve endings that allow us to feel touch, temperature, pain, pressure, and vibration, and it slows the loss of fluids from the body. The skin also shelters the hair follicles, which produce the hairs that cover most of the body’s surface, and it provides storage for a variety of substances. The skin, composed of several layers, ages quickly but is remarkably effective at renewing itself. In the top layer, the epidermis, most cells eventually reach the surface as the outermost layers at cells wear off. They are replaced in a time frame of roughly a month or two, in a continuous process that culminates in the loss of approximately 30,000 cells every minute throughout our lives. This translates into roughly eight pounds (4 kg) of dead material per year. Some features of our skin are, of course, more lasting. For example, we may have seemingly permanent moles and we may have scars that persist for years. These tissues, however, are not really skin. Moles are embedded within our skin but they are in fact benign growths that are typically composed of pigmented cells that do not follow the same lifecycle as true skin cells. Likewise, scars are repairs of deep cuts in our skin.

Unfortunately they do not give any reference there. Data should have been produced by carbon 14 dating. And yes, there are references

Radioactive carbon decays slowly, such that a given amount of carbon-14 halves every 6,000 years. So detecting the subtle change in the ratio of normal to naturally occurring radioactive carbon over just a few years is incredibly hard.
But Jonas Frisén of the Karolinska Institute in Stockholm, Sweden, says it can be done if one takes advantage of the signal left by nuclear testing, which spewed high levels of carbon-14 into the air during the Cold War.
By the time a halt was called to aboveground nuclear testing in 1963, levels of carbon-14 in the atmosphere had doubled beyond natural background levels, says Frisén. Since the halt, this has halved every 11 years. By taking this into account, one can see detectable changes in levels of carbon-14 in modern DNA, he says.
“Most molecules of the cell will turn over all the time. But DNA is a material that does not exchange carbon after cell division, so it serves as a time capsule for carbon,” Frisén says.

basically referring to a Cell 2005 paper

We therefore modified established DNA-extraction protocols to minimize the risk of carbon contamination (see Experimental Procedures). DNA samples were analyzed for purity in several ways; in addition to spectrophotometric analysis, the contents of all samples were analyzed by HPLC and the amount of total carbon (12C, 13C, and 14C) was determined during graphite preparation for isotope analysis by accelerator mass spectrometry.

They needed a minimum of 15 million cells for 14C analysis with the current sensitivity of accelerator mass spectrometry while it would be  interesting to repeat this study with single cell genome sequencing.

Purifying selection affect as much as 95% of the variants

New research shows that most genetic variants in the human genome are affected by purifying selection, so nothing “neutral”.

Pouyet, Aeschbacher et al. created a measure of genetic diversity that is only affected by selection or transmission bias. The results showed that negative selection influences as much as 85 percent of our genome, whereas transmission bias affects a majority of the rest of the genome. After removing these two biases, less than 5 percent of the human genome is found to evolve by chance. This suggests that while most of our genetic material is formed of non-functional sequences, the vast majority of it evolves indirectly under some type of selection.

Finding the allergy cause

Genomics did not really help to explain allergic mechanisms beyond IL33. But combining  now stem cell & immune cell Identity tracking looks like a promising strategy for identifying initial disease events. At least colleagues at the MDC  think so.

LifeTime – ein visionärer Vorschlag für ein EU-Flagschiff. Zuverlässig vorherzusagen, wann eine Krankheit ausbricht oder wie sie verläuft, erscheint wie ein Traum. Ein europäisches Konsortium will ihn Wirklichkeit werden lassen und dabei vor allem neue Technologien der Einzelzellbiologie nutzen. Führende Forscherinnen und Forscher haben daher einen Antrag für ein FET-Flagschiff mit dem Namen LifeTime eingereicht.

New insights by single-cell genomics

Congress report Annual AGD Meeting 2018, Potsdam Oct. 5–6

Welcome and Opening of Symposium by  Peter Nürnberg, President of the AGD and Joachim L. Schultze, Chair of the Program Committee.

Joachim L. Schultze
Peter Nürnberg

The AGD meeting was interesting and a great primer for all of us who are not directly working with single cells.

Maybe it is an unusual research field – dissecting single cells in the first stage is not a trivial task. And single cell  means single cell experiment that can be replicated only in other cells. The current readout is  RNA content at a given time while genomics and proteomics still need to be integrated. Experiments cover mainly abundant RNAs and for cost reasons only the 3′ ends. The statistical analysis usually is a 2 dimensional PCA (known to overfit noise) so this not a trivial approach at all. Newly identified cell cluster need careful confirmation as addressed in the talk of Andreas Schlitzer.

Continue reading New insights by single-cell genomics