Enlarge / The African Lungfish, showing it's thin, wispy fins. (credit: feathercollector)

When it was first discovered, the coelacanth caused a lot of excitement. It was a living example of a group of fish that was thought to only exist as fossils. And not just any group of fish. With their long, stalk-like fins, coelacanths and their kin are thought to include the ancestors of all vertebrates that aren't fish—the tetrapods, or vertebrates with four limbs. Meaning, among a lot of other things, us.

Since then, however, evidence has piled up that we're more closely related to lungfish, which live in freshwater and are found in Africa, Australia, and South America. But lungfish are a bit weird. The African and South American species have seen the limb-like fins of their ancestors reduced to thin, floppy strands. And getting some perspective on their evolutionary history has proven difficult because they have the largest genomes known in animals, with the South American lungfish genome containing over 90 billion base pairs. That's 30 times the amount of DNA we have.

But new sequencing technology has made tackling that sort of challenge manageable, and an international collaboration has now completed the largest genome ever, one where all but one chromosome carry more DNA than is found in the human genome. The work points to a history where the South American lungfish has been adding 3 billion extra bases of DNA every 10 million years for the last 200 million years, all without adding a significant number of new genes. Instead, it seems to have lost the ability to keep junk DNA in check.

Enlarge (credit: Aurich Lawson)

In 1972, Janet Rowley sat at her dining room table and cut tiny chromosomes from photographs she had taken in her laboratory. One by one, she snipped out the small figures her children teasingly called paper dolls. She then carefully laid them out in 23 matching pairs—and warned her kids not to sneeze.

The physician-scientist had just mastered a new chromosome-staining technique in a year-long sabbatical at Oxford. But it was in the dining room of her Chicago home where she made the discovery that would dramatically alter the course of cancer research.

Enlarge (credit: Aurich Lawson | Getty Images)

There are no wild ligers. Indeed, hybrids were once thought to be rare in nature—and of little consequence in an evolutionary sense. But now we know they can play an important role in speciation—the creation of new, genetically distinct populations.

As it turns out, hybridization in nature is quite common. Some 25 percent of plant species hybridize and some 10 percent of animals do the same.

“Hybridization as an event is rare,” said Jeremie Fant, a conservation scientist with the Chicago Botanic Garden who has worked on plant hybridization. “But in evolutionary history, it's been very common. Hybrids in the plant kingdom are everywhere. They are scattered through most lineages. When hybridization does occur, it can have important evolutionary impacts.”

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The basic outline of the interactions between modern humans and Neanderthals is now well established. The two came in contact as modern humans began their major expansion out of Africa, which occurred roughly 60,000 years ago. Humans picked up some Neanderthal DNA through interbreeding, while the Neanderthal population, always fairly small, was swept away by the waves of new arrivals.

But there are some aspects of this big-picture view that don't entirely line up with the data. While it nicely explains the fact that Neanderthal sequences are far more common in non-African populations, it doesn't account for the fact that every African population we've looked at has some DNA that matches up with Neanderthal DNA.

A study published on Thursday argues that much of this match came about because an early modern human population also left Africa and interbred with Neanderthals. But in this case, the result was to introduce modern human DNA to the Neanderthal population. The study shows that this DNA accounts for a lot of Neanderthals' genetic diversity, suggesting that their population was even smaller than earlier estimates had suggested.

Enlarge (credit: LEONELLO CALVETTI/SCIENCE PHOTO LIBRARY)

One of the challenges of working with ancient DNA samples is that damage accumulates over time, breaking up the structure of the double helix into ever smaller fragments. In the samples we've worked with, these fragments scatter and mix with contaminants, making reconstructing a genome a large technical challenge.

But a dramatic paper released on Thursday shows that this isn't always true. Damage does create progressively smaller fragments of DNA over time. But, if they're trapped in the right sort of material, they'll stay right where they are, essentially preserving some key features of ancient chromosomes even as the underlying DNA decays. Researchers have now used that to detail the chromosome structure of mammoths, with some implications for how these mammals regulated some key genes.

DNA meets Hi-C

The backbone of DNA's double helix consists of alternating sugars and phosphates, chemically linked together (the bases of DNA are chemically linked to these sugars). Damage from things like radiation can break these chemical linkages, with fragmentation increasing over time. When samples reach the age of something like a Neanderthal, very few fragments are longer than 100 base pairs. Since chromosomes are millions of base pairs long, it was thought that this would inevitably destroy their structure, as many of the fragments would simply diffuse away.

Enlarge / An artist's conception of one of the last mammoths of Wrangel Island. (credit: Beth Zaiken)

A small group of woolly mammoths became trapped on Wrangel Island around 10,000 years ago when rising sea levels separated the island from mainland Siberia. Small, isolated populations of animals lead to inbreeding and genetic defects, and it has long been thought that the Wrangel Island mammoths ultimately succumbed to this problem about 4,000 years ago.

A paper in Cell on Thursday, however, compared 50,000 years of genomes from mainland and isolated Wrangel Island mammoths and found that this was not the case. What the authors of the paper discovered not only challenges our understanding of this isolated group of mammoths and the evolution of small populations, it also has important implications for conservation efforts today.

A severe bottleneck

It’s the culmination of years of genetic sequencing by members of the international team behind this new paper. They studied 21 mammoth genomes—13 of which were newly sequenced by lead author Marianne Dehasque; others had been sequenced years prior by co-authors Patrícia Pečnerová, Foteini Kanellidou, and Héloïse Muller. The genomes were obtained from Siberian woolly mammoths (Mammuthus primigenius), both from the mainland and the island before and after it became isolated. The oldest genome was from a female Siberian mammoth who died about 52,300 years ago. The youngest were from Wrangel Island male mammoths who perished right around the time the last of these mammoths died out (one of them died just 4,333 years ago).

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The development of gene editing tools, which enable the specific targeting and correction of mutations, hold the promise of allowing us to correct those mutations that cause genetic diseases. However, the technology has been around for a while now—two researchers were critical to its development in 2020—and there have been only a few cases where gene editing has been used to target diseases.

One of the reasons for that is the challenge of targeting specific cells in a living organism. Many genetic diseases affect only a specific cell type, such as red blood cells in sickle-cell anemia, or specific tissue. Ideally, to limit potential side effects, we'd like to ensure that enough of the editing takes place in the affected tissue to have an impact, while minimizing editing elsewhere to limit side effects. But our ability to do so has been limited. Plus, a lot of the cells affected by genetic diseases are mature and have stopped dividing. So, we either need to repeat the gene editing treatments indefinitely or find a way to target the stem cell population that produces the mature cells.

On Thursday, a US-based research team said that they've done gene editing experiments that targeted a high-profile genetic disease: cystic fibrosis. Their technique largely targets the tissue most affected by the disease (the lung), and occurs in the stem cell populations that produce mature lung cells, ensuring that the effect is stable.

Enlarge / The spliceosome is a large complex of proteins and RNAs. (credit: NCBI)

Almost 1,500 genes have been implicated in intellectual disabilities; yet for most people with such disabilities, genetic causes remain unknown. Perhaps this is in part because geneticists have been focusing on the wrong stretches of DNA when they go searching. To rectify this, Ernest Turro—a biostatistician who focuses on genetics, genomics, and molecular diagnostics—used whole genome sequencing data from the 100,000 Genomes Project to search for areas associated with intellectual disabilities.

His lab found a genetic association that is the most common one yet to be associated with neurodevelopmental abnormality. And the gene they identified doesn’t even make a protein.

Trouble with the spliceosome

Most genes include instructions for how to make proteins. That’s true. And yet human genes are not arranged linearly—or rather, they are arranged linearly, but not contiguously. A gene containing the instructions for which amino acids to string together to make a particular protein—hemoglobin, insulin, albumin, whatever protein you like—is modular. It contains part of the amino acid sequence, then it has a chunk of DNA that is largely irrelevant to that sequence, then a bit more of the protein’s sequence, then another chunk of random DNA, back and forth until the end of the protein. It’s as if each of these prose paragraphs were separated by a string of unrelated letters (but not a meaningful paragraph from a different article).