Post by jenny on Jul 14, 2024 15:08:15 GMT
In 2018 an international team of scientists got their hands on a skin sample from a 52,000-year-old woolly mammoth that had been recovered from the permafrost in Siberia. They probed the sample with an innovative experimental technique that revealed the three-dimensional architecture of the mammoth’s genome. The resulting paper was published on Thursday in the journal Cell.
The technique had successfully captured the original geometry of long stretches of DNA, a feat never before accomplished with an ancient DNA sample.
The typical method for extracting ancient DNA from fossils produces short fragments of code composed of a four-letter molecular alphabet: A (adenine), G (guanine), C (cytosine), T (thymine). An organism’s full genome resides in cell nuclei, in long, unfragmented DNA strands called chromosomes. And, vitally, the genome is three-dimensional; as it dynamically folds with fractal complexity, its looping points of contact help dictate gene activity.
To have the actual architectural structure of the genome, which suggests gene expression patterns, is whole other level.
The information gleaned from such chromosome fossils will no doubt aid plans to “de-extinct” animals like the woolly mammoth. Three members of the research team are on the scientific advisory board of, and hold stock options in, Colossal Biosciences, a company that hopes to resurrect the mammoth, the Tasmanian tiger and the dodo. Colossal Biosciences did not provide funding or support for the research.
And 3-D genomic data will also be useful in efforts to save existing organisms from extinction by studying questions of how rapidly or not animals can adjust to warming or cooling patterns.
The researchers hypothesized that the mammoth had “spontaneously freeze-dried” in the cold of Siberia. The cells transitioned into a glasslike state, which prevented molecular movement and so preserved the chromosomes’ shape, or morphology, all the way down to 50-nanometer genomic loops.
By combining polymer physics and PaleoHi-C data, the researchers reconstructed how woolly mammoth chromosomes folded and fluctuated inside cell nuclei tens of thousands of years ago, building on earlier research that probed the 3-D architecture of whole genomes. A genome is like a book containing all of an organism’s genetic information; DNA sequencing extracts and reads individual pages of the book, but without page numbers. The new technique, called Hi-C, puts the pages in order.
Researchers studied the way the technique worked on how degraded and contaminated samples could yield a 3D map. Once they had the 3-D signal, they could examine how the 52,000-year-old mammoth’s genome was folded. One remarkable finding was that classic features of modern chromosomes, at many scales, were preserved.
The elephant and mammoth genomes were strikingly similar: Each had 28 chromosomes — not surprising, yet a valuable confirmation. However, a comparison of the two 3-D genomes showed that about 800 genes in skin — 4.1 percent of the total — exhibited differing activity profiles. One class of differing genes pertained to hair follicle development and hair growth regulation.
I've abridged a NYT article to create this - if you want to read the more detailed original, with researchers' names etc, it's here.
The technique had successfully captured the original geometry of long stretches of DNA, a feat never before accomplished with an ancient DNA sample.
The typical method for extracting ancient DNA from fossils produces short fragments of code composed of a four-letter molecular alphabet: A (adenine), G (guanine), C (cytosine), T (thymine). An organism’s full genome resides in cell nuclei, in long, unfragmented DNA strands called chromosomes. And, vitally, the genome is three-dimensional; as it dynamically folds with fractal complexity, its looping points of contact help dictate gene activity.
To have the actual architectural structure of the genome, which suggests gene expression patterns, is whole other level.
The information gleaned from such chromosome fossils will no doubt aid plans to “de-extinct” animals like the woolly mammoth. Three members of the research team are on the scientific advisory board of, and hold stock options in, Colossal Biosciences, a company that hopes to resurrect the mammoth, the Tasmanian tiger and the dodo. Colossal Biosciences did not provide funding or support for the research.
And 3-D genomic data will also be useful in efforts to save existing organisms from extinction by studying questions of how rapidly or not animals can adjust to warming or cooling patterns.
The researchers hypothesized that the mammoth had “spontaneously freeze-dried” in the cold of Siberia. The cells transitioned into a glasslike state, which prevented molecular movement and so preserved the chromosomes’ shape, or morphology, all the way down to 50-nanometer genomic loops.
By combining polymer physics and PaleoHi-C data, the researchers reconstructed how woolly mammoth chromosomes folded and fluctuated inside cell nuclei tens of thousands of years ago, building on earlier research that probed the 3-D architecture of whole genomes. A genome is like a book containing all of an organism’s genetic information; DNA sequencing extracts and reads individual pages of the book, but without page numbers. The new technique, called Hi-C, puts the pages in order.
Researchers studied the way the technique worked on how degraded and contaminated samples could yield a 3D map. Once they had the 3-D signal, they could examine how the 52,000-year-old mammoth’s genome was folded. One remarkable finding was that classic features of modern chromosomes, at many scales, were preserved.
The elephant and mammoth genomes were strikingly similar: Each had 28 chromosomes — not surprising, yet a valuable confirmation. However, a comparison of the two 3-D genomes showed that about 800 genes in skin — 4.1 percent of the total — exhibited differing activity profiles. One class of differing genes pertained to hair follicle development and hair growth regulation.
I've abridged a NYT article to create this - if you want to read the more detailed original, with researchers' names etc, it's here.