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Problems Of Genetics

A key figure in the field of evolutionary biology, William Bateson (1861–1926) revived Mendelian methods of analysis to develop Darwin's theory of evolution, thereby pioneering the study of genetics. In these lectures, published at Yale in 1913, Bateson systematically chronicles the era's conflicting and developing theories on taxonomy, speciation, variation and hybridisation, and includes his own thoughts on continuous and discontinuous variation and its causes. Drawing on the comparative physiology and anatomy of species that he knew from his wide experience, citing detailed examples from across the taxonomic kingdoms, Bateson brings to life this exciting time in biology. Because the theories central to the modern understanding of genetics, heredity and evolution were formed at this time, this work remains valuable and relevant to students of biology and the history of science.

Genetic-editing Of Chickens Protects Them From Catching The Flu

The genome of the humble chicken has been edited to protect them from avian influenza. When the edited birds were then exposed to avian flu they were largely resistant to it, with nine in 10 birds uninfected. 'This promises a new way to make permanent changes in the disease resistance of an animal,' says Mike McGrew at the Roslin Institute, University of Edinburgh, who was involved in the research.

An H5N1 flu strain is currently killing huge numbers of wild birds across Asia, Europe and the Americas, as well as occasionally devastating farmed poultry and killing mammals. 'There is a growing fear that bird flu could jump to humans and lead to another pandemic,' says McGrew. A gene-editing strategy could both protect poultry and reduce the risk of bird flu spreading to poultry farmers and wild birds.

Currently, one of the best ways to protect poultry from catching avian flu is by keeping them under cover, away from wild birds that can transmit the disease. However, this isn't ideal for the birds' wellbeing. Vaccination is another possibility, but is challenging in terms of cost and practicality, and flu can mutate to evade vaccines.

Gene editing offers a new way to protect poultry and was achieved using Crispr–Cas9 to edit the gene that produces the protein ANP32A, as it is known to be hijacked by the virus to assist it in replicating. The edit changed two amino acids in the ANP32A protein so that a flu polymerase enzyme could no longer bind to it. Edited birds were mated to produce offspring that were resistant to the virus. These chickens showed no changes in growth, behaviour or health.

'This strategy could be used not just for H5N1 bird flu, but for any of the strains, because it's fundamental to the way that the virus works,' said Wendy Barclay, a virologist at Imperial College London, speaking at a press briefing.

Her earlier studies identified the ANP32 protein family as essential for flu replication in human cells. Her group also previously reported that shorter human ANP32 proteins do not support bird flu well and the researchers hypothesised that changing these proteins in birds might protect against the virus.

The edit was not a complete success, however, as not every bird was protected against flu. It may be possible to make chickens resistant to the flu virus, but this will require more robust edits that completely stamp out viral replication, says Barclay. This was emphasised by the discovery of viral mutants that used related ANP32 proteins to continue replicating.

Disabling three ANP32 genes led to chicken cells that were completely resistant to the flu virus, but no birds have been bred with these changes yet.

A new English law in 2023 set out a regulatory path for gene-edited plants and animals, which would include flu-resistant poultry. Edited chickens are still some way from supermarket shelves, however.

'The results here are really promising,' says Richard Webby, an expert in influenza in animals and birds at St. Jude Children's Research Hospital in Memphis, US. 'This particular edited chicken is not ready for primetime, and there's still a lot of research to do to see if the approach will work. But producing a flu-resistant chicken would be an incredible advance.'

'From a public health perspective, anything we can do to reduce the contact of humans with these animal flu viruses is positive,' he says.

Webby adds that it 'is somewhat concerning that the virus mutated in ways that made it a little more adapted to mammal cells, but we probably could have predicted that based on the biology'.

The team says that pigs are another possible target for editing in flu resistance, as they have been linked to the emergence of flu pandemics such as in 2009. The researchers now plan to edit the remaining ANP32 genes in chickens to stop the proteins being hijacked by the flu virus.

Inbreeding Can Be Beneficial In The Long Run

image: Reindeer have managed to adapt to life on Svalbard, despite the fact that they have only been on the islands for roughly 8,000 years. But will they be able to adapt to the rapid climate changes? View more 

Credit: Photo: Bart Peeters

"Of all the subspecies of reindeer found in the high north, the Svalbard reindeer has the most inbreeding and the lowest genetic diversity," says Nicolas Dussex, a postdoc at Norwegian University of Science and Technology´s (NTNU) Department of Natural History.

It was only 7000-8000 years ago that the first reindeer migrated to Svalbard, most likely from Russia via Novaya Zemlya and the islands of Franz Josef Land. Perhaps there were no more than a few animals that established themselves on the arctic archipelago. Evolutionary theory suggests this is a poor starting point since inbreeding can quickly lead to an accumulation of harmful mutations and genetic variants followed by disease and death.

Rapid adaptation to an extreme environment

But this has not prevented the Svalbard reindeer from evolving into what is today a viable population of more than 20,000 animals.

"Despite the low genetic diversity, they have managed to develop a number of adaptations to life in the High Arctic. They are, for example, smaller in size and have shorter legs than other northern reindeer and caribou subspecies," says Dussex.

The ability to digest mosses in the absence of lichens, and to adjust their circadian rhythm to the extreme seasonal variations on Svalbard, are also traits the Svalbard reindeer have developed over the relatively short time they have lived isolated on the archipelago. Now, researchers at NTNU and collaborating institutions have analyzed genetic samples from 91 reindeer to see how they differ from their relatives on the mainland.

"Populations living on isolated islands are often small and are well-suited studying genetic problems. The Svalbard reindeer has been isolated for at least 7000 years and has a very high degree of inbreeding. In addition, they were nearly extinct in the early 1900s due to excessive hunting," says Michael D. Martin, a professor at NTNU's Department of Natural History.

Getting rid of harmful mutations

This near-extinction, where only a few individuals with their unique genetic variants survive, is called a bottleneck in population biology.

"In this case, we are dealing with a population that suffers from a high degree of inbreeding, which is usually bad news for a small population. But inbreeding can also help a population to get rid of harmful mutations, a phenomenon technically called 'purging'," says Martin.

In a population with a high degree of inbreeding, offspring are more likely to inherit harmful mutations from both mother and father. Therefore, these "dangerous" mutations more quickly manifest in the form of genetic diseases and poorer health. Offspring carrying these mutations become less "fit", and they will either die before they have the chance to reproduce or they will have fewer offspring. Consequently, these dangerous mutations are less likely to be passed on to subsequent generations.

"Paradoxically, in the long run, inbreeding can be beneficial," says Dussex.

Punctuated evolution or steady and continuous?

Similar phenomena have been observed elsewhere in nature. In New Zealand, Kakapo parrots (Strigops habroptilus), which had lived isolated on the islands for at least 10,000 years, became endangered after the arrival of non-native species brought to the islands by humans. In 1995, there were only 60 individuals left, but today the population has grown to around 200. Here too, Dussex and his colleagues found that harmful genetic variants had disappeared from the population thanks to a long period of inbreeding.

"This is important knowledge when it comes to population management. The fact that the Svalbard reindeer is in relatively good genetic condition considering harmful mutations, is good news," says Brage Bremset Hansen, professor of conservation biology at NTNU's Department of Biology and Center for Biodiversity Dynamics. Hansen is also a senior researcher at the Norwegian Institute for Nature Research (NINA).

This knowledge about the Svalbard reindeer can also change the way researchers study the effects of genetic bottlenecks, Dussex said.

"What we still do not know enough about is how quickly such harmful mutations are selected against. We will continue to work on this, using DNA samples collected from bone remains and antlers of animals that lived several thousand years ago. This way, we can see whether these mutations have disappeared quickly over a few centuries or if it has happened gradually over several thousand years," he said.

The researchers are also very interested in examining the development of beneficial mutations, which have allowed the Svalbard reindeer to adapt to the unique ecosystem.

"This is a 'work in progress'," says Martin, who also worked closely with researcher Mathilde Le Moullec, who over past years did the fieldwork to collect most of the bone samples from various locations on Svalbard.

Climate change may be too fast

It is far from certain that the Svalbard reindeer will be able to adapt as well to the rapid changes that result from global warming. The adaptations the reindeer have developed for the extreme arctic climate may fall short as the archipelago is now rapidly warming, which is changing both snow cover and vegetation.

"Global warming is causing Svalbard's climate to change faster than anywhere else in the world. Even though our results show that the Svalbard reindeer managed to adapt relatively quickly to a completely new environment after they colonized the islands, they might have trouble adapting to today's rapid warming. They may have simply lost too much genetic variation," says Hansen.

This also applies to other terrestrial animals that have limited opportunities to move as climate change makes life difficult for them.

"But this work now provides us with a better basis for understanding how quickly species can adapt to new environments," says Martin.

Reference:

Adaptation to the High-Arctic island environment despite long-term reduced genetic variation in Svalbard reindeer. Nicolas Dussex, Ole K. Tørresen, Tom van der Valk et al. IScience  VOLUME 26, ISSUE 10, 107811, OCTOBER 20,2023. DOI:10.1016/j.Isci.2023.107811

Method of Research

Data/statistical analysis

Subject of Research

Not applicable

Article Title

Adaptation to the High-Arctic island environment despite long-term reduced genetic variation in Svalbard reindeer

Article Publication Date

1-Sep-2023

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