Interview to our November AaRC-TikTalk speaker Marianne Dehasque

The woolly mammoth (Mammuthus primigenius) was a greatly successful species characteristic of the Pleistocene megafauna in Eurasia, roaming around the whole northern part of the continent for millennia (1), reaching up to Mediterranean seashores during their highest expansion range (2), and even migrating to the American continent and again back to Eurasia through the Bering land bridge due to sea level downfall during the last Ice Age (3). The causes of their final disappearance, first from continental mainland and subsequently from their last northern Arctic refugia remain, however, debated. Dr. Marianne Dehasque shared with us one of her last research studies where she tried to elucidate what happened to the last woolly mammoths at the genomic level (4). In this way, we can learn unvaluable lessons of how near-extinction events affect animal populations in the present, and improve conservation efforts to preserve endangered species.

They first started by selecting 21 woolly mammoths to study, of which 14 were dated between 9.3 and 4.3 thousand years-before-present belonged to a population trapped into the Wrangel Island after it got separated from the Eurasian continent. These individuals lived after the severe bottleneck that happened when the island got isolated around 10 thousand years ago due to rising sea levels. The remaining 7 mammoths found in the Siberian mainland were dated to between 12 to 50 thousand years ago. These two subgroups were considered sufficiently separated in time so as to compare how living in a small isolated island during the last living generations of woolly mammoths would have affected them genetically. In a sense, Wrangel island could have been a heavenly peaceful refuge for the last surviving mammoths, but a genetic hell at the same, with a pervasive accumulating inbreeding effect across generations that might have ultimately caused their final extinction. Was Wrangel island ultimately a sinister trap where woolly mammoths were obliged to extreme inbreeding up until they were rendered biologically unable to reproduce further? Did genomic erosion kill the last surviving woolly mammoths?

Dehasque and collaborators found proof of an increased homozygosity and genetic deletions in Wrangel island mammoths compared to older mainland relatives, as expected due to loss of genetic diversity after the extreme bottleneck caused by the isolation in a small island up in the Arctic. They argued that this is probably caused by increased inbreeding, i.e. mating between close relatives, where genetic diversity gets eroded and similar genotypes get combined forming long regions of homogenous invariant genomic sequences across the population. This was even more prevalent in regions known to harbor genes crucial for immune response, weakening their ability to adapt to pathogens and derived illnesses.

However, after the initial strong bottleneck effect, they found weak evidence of sustained genomic erosion, where homozygosity kept accumulating but at a much slower pace. To explain this, they suggest a fast recovery after the initial bottleneck and a subsequent stabilization of the isolated Wrangel island population after around 20 generations, with still some level of inbreeding but mostly due to mating with distant relatives. Interestingly and supporting this hypothesis, they found an increased segregation of mutations with mild deleterious effects, but a reduced proportion of highly damaging polymorphisms in Wrangel island mammoths, a finding that they linked to the presence of purging through strong selection against homozygous deleterious mutations. Paradoxically, this could help the endurance of highly inbreed populations through time.

Dehasque and collaborators inferred that this population quickly recovered after a strong bottleneck caused by land isolation, initially suffering a steep increase in inbreeding and deleterious genetic load hindering their adaptive abilities as seen in immune-related genomic regions, but progressively recovering to a stable population that survived for millennia thanks to pervasive purging of highly damaging mutations and lowered inbreeding effects. However, as they did not analyze the very last woolly mammoths surviving in the Wrangel island, the final cause of the extinction of the woolly mammoths living in Wrangel island remains, as the authors emphasize, uncertain. It might have been caused by a sudden change in environmental conditions or pathogen outbreak leading to high mortality rates, or maybe the last generations of woolly mammoths suffered again a strong bottleneck effect with increased deleteriousness that rendered them finally unable to recover.

References

1. Nyström, V. et al. Temporal genetic change in the last remaining population of woolly mammoth. Proceedings of the Royal Society B: Biological Sciences 277, 2331–2337 (2010).
2. Álvarez-Lao, D. J., Kahlke, R. D., García, N. & Mol, D. The Padul mammoth finds — On the southernmost record of Mammuthus primigenius in Europe and its southern spread during the Late Pleistocene. Palaeogeogr Palaeoclimatol Palaeoecol 278, 57–70 (2009).
3. Debruyne, R. et al. Out of America: Ancient DNA Evidence for a New World Origin of Late Quaternary Woolly Mammoths. Current Biology 18, 1320–1326 (2008).
4. Dehasque, M. et al. Temporal dynamics of woolly mammoth genome erosion prior to extinction. Cell 187, 3531-3540.e13 (2024).
   
   

Below, Marianne shared with us further details about her profile, career, prospects and future projects:

1. Briefly introduce yourself. What is your origin story for how you got into science?
Hi, I’m Marianne, a postdoctoral researcher at Uppsala University in Sweden. My current work focuses on the genomics of feralization in sheep, using both contemporary and ancient DNA. Before this, I completed my PhD at Stockholm University, where I studied the genomics of the last woolly mammoth population on Wrangel Island. If you created a word cloud of my research interests, you’d probably see words like “woolly,” “island,” and “ancient DNA” standing out.

2. How and/or why did you start working on this project?
The mammoth project has already been going on for over 20 years. I joined the team as a PhD student in 2018. I sometimes joke that “I am number four”, referring to being Love Dalén’s fourth PhD student working on mammoths. What makes the Wrangel Island mammoth population so fascinating -aside from being the enigmatic last woolly mammoth population – is how closely their story mirrors the challenges of many present-day species threatened by climate change and habitat loss. This makes the Wrangel mammoths an excellent system to study and test long-standing hypotheses on the evolutionary processes in small, declining populations. The insights we gain can hopefully also contribute to the field of conservation genomics and help us better understand how to protect endangered species today.

3. Were there any major challenges in this project? How did you overcome them?
Like most scientific projects, this one had its fair share of challenges—some bigger than others. One standout moment involves a mammoth nicknamed “Lonely Boy.” I wrote a piece about our adventures with Lonely Boy in The Conversation, but to keep things brief, we invested a lot of time (and money!) into analyzing a precious sample that, in the end, turned out to be a completely average mammoth.

4. What do you think are the main take-home messages of this project?
I would say there are two take-home messages in this project: The first one being that the mammoths on Wrangel Island were not doomed by their small population size. Instead, a sudden and short event likely caused the population’s demise. This challenges earlier hypotheses, suggesting that an accumulation of genomic defect led to the Wrangel mammoth’s extinction. Those earlier studies relied on limited data, such as small markers or a single Wrangel Island genome. In our study, we analyzed a dataset of 21 serially sampled mammoth genomes, providing us a much more complex and nuanced understanding of the mammoth’s extinction. Second, despite quickly recovering from a sudden population decline, the Wrangel mammoths suffered from inbreeding depression for over 6,000 years. This is an important finding for conservation – as it implies that just restoring population size may not be sufficient to ensure a viable population. Instead, active genetic monitoring is essential to safeguard against long-term population bottleneck-related issues.

5. What do you think is missing in the field that you would like to work on?
Most ancient genomic research has focused on SNP’s and small indels, but the world of structural variants remains largely unexplored. I believe that further exploring this type of genetic variation could reveal exciting new insights into evolutionary processes over time.

6. Where do you see yourself in the near future?
In a sunnier place than Sweden. Preferably somewhere with a nice beach.