Tag: dna

Histones

Work on the structure and function of histones in ancient, simple cells has made the central importance of these proteins to gene regulation even clearer. Billions of years ago, archaea were already using histones, but with looser rules and much more variety. By curving the DNA around the nucleosome, the histones prevent it from clumping together and keep it functional. With more DNA, cells could wrap more nucleosomes and enable the histones to reduce more copper, which would support more mitochondrial activity. It wasn’t just that histones allowed for more DNA, but more DNA allowed for more histones.

Engram

Almost all neuroscientists base their search—for the physical basis of memory (the engram)—on the assumption that temporal-pairing causes learning. They are dedicated to this assumption—even though, as Rescorla pointed out 50 years ago, experimental attempts to define temporal-pairing have always failed. This failure is as striking now as it was 50 years ago. Anything that gets neuroscientists to abandon the idea that temporal-pairing is a useful scientific concept is a step toward discovering the physical basis of memory. Each neuron contains billions of (almost) incomprehensibly-tiny molecular machines. Molecular biologists have developed an astonishing array of techniques for visualizing/manipulating the actions of these little machines. These techniques will allow molecular biologists to follow the machines inside this huge neuron to the engram—to the tiny machine that encodes the experience-gleaned facts so that these learned/remembered facts can inform later behavior.

2021-11-19: This feels like a really big deal:

Biology feels different right now. New broadly enabling technologies and tools are driving forward progress in nearly every specific field at a rapid pace. The large scale adoption and application of a powerful set of common tools has created a virtuous cycle of further technology refinement and engineering. The rate of iteration is increasing, and previously intractable problems are now within reach. While RNA-seq and MPRAs are both valuable approaches, they come with some limitations. Fundamentally, each measurement represents a single static slice of a dynamic process which is only inferred by attempting to piece together the slices. The quality of the reconstruction is limited by sampling density. What if we could measure these systems continually as they occurred in a way that didn’t require destructive sampling? Here, the fundamental idea is that “DNA is the natural medium for biological information storage, and is easily ‘read’ through sequencing.” This forms the basis for this new technology: ENGRAM (ENhancer-driven Genomic Recording of transcriptional Activity in Multiplex). The workflow of this technique is very similar to that of the MPRA introduced above, but with an important twist. Instead of destroying the cell and sequencing a ratio of barcodes, the transcription event is recorded by the insertion of a barcode into a locus of DNA in the cell via prime editing. They went further and showed that they could effectively multiplex this technique by reading out all 3 signals in response to stimulants in a single population of cells. Even more, they showed a proof-of-concept for reading out the order in which events occurred.

Mendelian randomization

by employing innate genetic differences between people—an inborn susceptibility to alcohol, say, or to higher cholesterol levels in the arteries—they can now mimic, at much less effort and expense, the kinds of large trials that would be necessary to determine if an HDL-lowering medicine is really beneficial. The new technique, called Mendelian randomization, is already being used by drug companies to make billion-dollar decisions about which drugs to pursue. What may worry Davey Smith and others most is that as genetic databases have multiplied, tying genes to virtually any imaginable biological or even behavioral variable, studies of cause and association have become almost effortless.

The University of Bristol hosts a platform called MR-Base that lets anyone carry out virtual experiments without collecting any new data.

“You can do these studies now, sitting at your desk, in 10 minutes. It’s just too easy. Because of the flood of studies coming out, it may very well fall into disrepute.”

Essential gene evolution

Essential genes are often thought to be frozen in evolutionary time — evolving only very slowly if at all, because changing or dying would lead to the death of the organism. 100s of millions of years of evolution separate insects and mammals, but experiments show that the Hox genes guiding the development of the body plans in Drosophila fruit flies and mice can be swapped without a hitch because they are so similar. This remarkable evolutionary conservation is a foundational concept in genome research.

But a new study turns this rationale for genetic conservation on its head. Researchers at the Fred Hutchinson Cancer Research Center in Seattle reported last week in eLife that a large class of genes in fruit flies are both essential for survival and evolving extremely rapidly. In fact, the scientists’ analysis suggests that the genes’ ability to keep changing is the key to their essential nature. “Not only is this questioning the dogma, it is blowing the dogma out of the water

China civilization origins

Shimao is now the largest known Neolithic settlement in China with art and technology that came from the northern steppe and would influence future Chinese dynasties.

Together with recent discoveries at other prehistoric sites nearby and along the coast, Shimao is forcing historians to rethink the beginnings of Chinese civilization—expanding their understanding of the geographical locations and outside influences of its earliest cultures. Shimao is one of the most important archaeological discoveries of this century. It gives us a new way of looking at the development of China’s early civilization. Carbon-dating determined that parts of Shimao, as the site is called (its original name is unknown), date back 4300 years, 2000 years before the oldest section of the Great Wall—and 500 years before Chinese civilization took root on the Central Plains, several 100 km to the south.

2023-06-07: The genetic roots go back even further

We now know that the Han, 95% of the citizens of today’s People’s Republic of China, are scions of hunters and foragers who roamed the Yellow and Yangzi river valleys at the end of the last Ice Age, 12 ka BP. Today’s Chinese carry DNA startlingly similar to an individual buried in Tianyun Cave, near modern Beijing, 40 ka BP. China might not have the oldest continuous recorded history (Mesopotamia owns this distinction). But it comes close, and on the far more astonishing scale of 10s of 1000s of years, the Chinese people’s biological continuity knows no parallel.

Hybrid Fish

Sturddlefish go shockingly far beyond classic crossbreeds like mules and ligers, whose parent species sit close together on the tree of life. Sturddlefish result from the merger of different taxonomic families. It’s like if they had a cow and a giraffe make a baby. Then he quickly corrected himself, because the lineages of those 2 ruminants split only 40 ma ago. The evolutionary paths of paddlefish and sturgeons diverged 184 ma ago. For those fish to breed is more like if a human came out of a platypus egg.