“Polygenic Adaptation”
“CRISPR-Cas9 is a method for quickly and accurately editing the genome of virtually any living thing… “
Article by Adam Bluestein / Illustration by Jamie Cullen
Significance
We discovered that contrary to other bird species and most other animals, all examined songbird lineages contain a different number of chromosomes in the somatic and germline genomes. Their germ cells have an additional germline-restricted chromosome (GRC). GRCs contain highly duplicated genetic material represented by repetitive elements and sequences homologous to unique regions of the somatic genome. Surprisingly, GRCs even in very closely related species, vary drastically in size and show little homology. We hypothesize that the GRC was formed as an additional parasitic microchromosome in the songbird ancestor about 35 million years ago and subsequently underwent significant changes in size and genetic content, becoming an important component of the germline genome.
An unusual supernumerary chromosome has been reported for two related avian species, the zebra and Bengalese finches. This large, germline-restricted chromosome (GRC) is eliminated from somatic cells and spermatids and transmitted via oocytes only. Its origin, distribution among avian lineages, and function were mostly unknown so far. Using immunolocalization of key meiotic proteins, we found that GRCs of varying size and genetic content are present in all 16 songbird species investigated and absent from germline genomes of all eight examined bird species from other avian orders. Results of fluorescent in situ hybridization of microdissected GRC probes and their sequencing indicate that GRCs show little homology between songbird species and contain a variety of repetitive elements and unique sequences with paralogs in the somatic genome. Our data suggest that the GRC evolved in the common ancestor of all songbirds and underwent significant changes in the extant descendant lineages.
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In 2018, psychology PhD student William McAuliffe co-published a paper in the prestigious journal Nature Human Behavior. The study’s conclusion — that people become less generous over time when they make decisions in an environment where they don’t know or interact with other people — was fairly nuanced.
But the university’s press department, perhaps in an attempt to make the study more attractive to news outlets, amped up the finding. The headline of the press release heralding the publication of the study read “Is big-city living eroding our nice instinct?”
From there, the study took on a new life as stories in the press appeared with headlines like “City life makes humans less kind to strangers.”
This interpretation wasn’t correct: The study was conducted in a lab, not a city. And it measured investing money, not overall kindness.
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Want remarkably clear insights into genetics and public health with a bare minimum of reading? Well, some corners of Twitter have recently become an incredible resource if you’re interested in learning something about predictive statistics, epidemiology, genomics, and population genetics. There are no better examples of this than the tweetorials that Dr. Cecile Janssen posts. Dr. Janssen is a professor of translational epidemiology in the department of Epidemiology of the Rollins School of Public Health, Emory University, and her website, like her posts, contains insightful guides for thinking critically about DNA sequence data, heritability and health.
If you would like some key insights into predicting complex traits from DNA in a handful of tweets, follow this link: Why it is so hard to predict complex diseases and traits from DNA?
For a slightly longer read, here’s her article from WIRED on how DNA is best applied: DNA tells great stories -- about the past, not future
And a more advanced read, still aimed at a fairly general audience: Designing babies through gene editing: science or science fiction?
It is common for articles to claim that “the gene for” some trait or disease has been identified. Usually they actually mean that an association has been found between an uncommon genetic variant found in, or near, a gene and some trait or disease. These kinds of articles are becoming increasingly common because Genome-Wide Association Studies (GWAS) are becoming cheaper and more common. Though GWAS yield important insights their results can be misleading because ancestral relationships between individuals in the study can create signals that can be misinterpreted as association with the trait being studied. This phenomenon is very powerful and one reason why it is important to have a diverse group of individuals in any genetic study. Underlying ancestral relationships are known as “population structure” and serious thought is required to ensure that it doesn’t skew GWAS results. The paper below is a scientific review article (in an excellent journal with exceptional authors) and not exactly easy reading, but it was written for a broad audience and worth considering the next time you see an article discussing the identification of “the genes for” something or other, even if it appears in Genome-Media.
-RPR
Great care is needed when interpreting claims about the genetic basis of human variation based on data from genome-wide association studies.
Human height is the classic example of a quantitative trait: its distribution is continuous, presumably because it is influenced by variation at a very large number of genes, most with a small effect (Fisher, 1918). Yet height is also strongly affected by the environment: average height in many countries increased during the last century and the children of immigrants are often taller than relatives in their country of origin – in both cases presumably due to changing diet and other environmental factors (Cavalli-Sforza and Bodmer, 1971; Grasgruber et al., 2016; NCD Risk Factor Collaboration, 2016). This makes it very difficult to determine the cause of geographic patterns for height, such as the ‘latitudinal cline’ seen in Europe (Figure 1).
These viruses weren’t supposed to affect humans. They were supposed to ride along inside bacteria — unobtrusive hitchhikers taking advantage of another microbe’s machinery. But that wasn’t what Dr. Paul Bollyky and his colleagues saw in their lab dishes three or four years ago. The viruses seemed to be changing the behavior of human immune cells. Instead of gobbling up bacteria as they normally did, white blood cells just sat there.
“They basically don’t eat anything. They don’t move around much either,” said Bollyky, an immunologist and infectious disease specialist at Stanford University. “They would just ignore … the bacteria that were in the dish with them.”
Now, with a paper published Thursday in Science, what began as a chance observation has yielded a startling window into the inner lives of infections — one in which viruses tag-team with bacteria to trick the immune system by providing a decoy. Bollyky describes it as having someone trip the fire alarm so that the rest of the team can pull off a robbery in the chaos that ensues.
Matt Richtel, The New York Times
Cancer immunotherapy drugs, which spur the body’s own immune system to attack tumors, hold great promise but still fail many patients. New research may help explain why some cancers elude the new class of therapies, and offer some clues to a solution.
The study, published on Thursday in the journal Cell, focuses on colorectal and prostate cancer. These are among the cancers that seem largely impervious to a key mechanism of immunotherapy drugs.
The drugs block a signal that tumors send to stymie the immune system. That signal gets sent via a particular molecule that is found on the surface of some tumor cells.
The trouble is that the molecule, called PD-L1, does not appear on the surface of all tumors, and in those cases, the drugs have trouble interfering with the signal sent by the cancer.
In a single drop of water from Lake Ontario, you can find an abundance of algae. In these algae, scientists in 2015 found a new virus belonging to an enigmatic group called giant viruses. And nested inside these giant viruses, scientists have now found yet more novel viruses—three tiny ones that they have named CpV-PLV Larry, Curly, and Moe.
“I originally named them to see if I can get away with it,” says Joshua Stough, now a postdoctoral research fellow at the University of Michigan. He’s a co-author of a new paper describing and naming the Three Stooges, so, in fact, he has gotten away with it.
““The most common form of malignant brain cancer—called a glioblastoma—is notoriously wily and considered the deadliest human cancer. Glioblastomas charge their way into normal brain tissue diffusely and erratically, making them surgical nightmares. And they mutate at such a rapid rate that most currently available cancer treatments can't keep up with them. Even neighboring tumor cells can be genetically distinct, and therefore hard to target with a single therapy.
Survival rates from glioblastomas enjoyed a modest bump in the 1980s when radiation became a standard part of the treatment protocol. Patients could expect to live for nearly another year after diagnosis, up from just four to six months. The introduction of the chemotherapy drug temozolomide in the 2000s increased survival another few months. But since then patient survival rates have stalled… many experts insist the key to beating glioblastoma will entail personalizing care to a patient’s individual tumor and the particular molecular signature of a cancer.
One method of testing cancer therapies, including glioblastomas, has been so-called “ex vivo” cancer models, in which malignant cells are probed in the lab. Also known as tumor “avatars,” they allow researchers to test a drug on patients’ cancer cells before introducing it into their bodies. A number of ex vivo models have been tried over the years: culturing tumor cells in Petri dishes; grafting them into animal models; even growing “organoids” (three-dimensional tumors grown on a supporting matrix). These techniques have seen varying success depending on the tumor type at hand, but none have proven especially helpful for glioblastoma.
A report on new research technology published recently in the journal Nature Biomedical Engineering may address the limitations of previous ex vivo approaches. In short, researchers have concocted a glioblastoma-on-a-chip. Chip-based models of various organs and diseases—including many cancers—have debuted in the last few years. They are constructed by lining a plastic microchip with live human cells that mimic a particular organ or disease in order to simplify, cheapen and increase the efficiency of drug testing. The Wyss Institute at Harvard University and other groups have made impressive headway in developing a number of chip-based biologic models. Chip models of the lung, the intestine, skin, bone marrow ALS—even the blood-brain barrier—have been tested.”
ROXANNE KHAMSI (WIRED)
“Even if cancer therapies kill most of the cells they target, a small subset can survive, largely thanks to genetic changes that render them resistant. In advanced-stage cancer, it’s generally a matter of when, not if, the pugnacious surviving cells will become an unstoppable force. Gatenby thought this deadly outcome might be prevented. His idea was to expose a tumor to medication intermittently, rather than in a constant assault, thereby reducing the pressure on its cells to evolve resistance.“
