As a species that "just" became extinct 4,000 years ago, how did the mammoth disappear from the face of the earth? This question has always fascinated scientists. On Wrangel Island, isolated from the mainland, the last mammoth population once lived, making it an ideal place for researchers to find out.
A recent study published in the journal Cell has overturned long-held speculation that isolated mammoth populations on Wrangel Island eventually became extinct due to inbreeding and genetic defects. In other words, genetic problems caused by inbreeding may not have been the cause of their extinction, and their story is more complex than previously understood.
Written by | Wood wood
In the movie "Ice Age", the mammoth Manny, the sloth Sid and the saber-toothed tiger Diego, three animal protagonists who were originally natural enemies, help each other survive and grow together in the harsh natural environment.
Among them, Manny, who is huge in size, is taciturn and mild-mannered, and hides deep down his grief over the loss of his family. Behind this story full of warmth and humor, it is also implied that during that distant ice age, the great changes in the natural environment had a profound impact on the fate of some species.
Movie "Ice Age"
In fact, the woolly mammoth (Mammuthus primigenius) was one of the most widespread large herbivores on Earth during the last ice age. However, by the end of the Late Pleistocene (about 10,000 years ago), they disappeared from most of the Earth's continents. There are only a few isolated populations, cut off from the continent due to global sea level rise due to climate change. One of the most important populations, on Wrangel Island, an island between the present-day East Siberian Sea and the Chukchi Sea, was last extinct until about 4,000 years ago.
Placed throughout geological time, it seems to be a good understanding that the global extinction of a species is caused by drastic climate change on a planetary scale. But why did the woolly mammoth, which has survived on Wrangel Island for almost 6,000 years, not escape extinction?
We can't help but ask, what happened to the woolly mammoth on Wrangel Island during the period when human civilization had begun to conceive and develop?
The story of the last years
The isolated environment of Wrangel Island has allowed us to obtain well-preserved mammoth remains and provides the opportunity to study how this small population survived for a long time and how it eventually became extinct. This, combined with advances in gene sequencing technology in recent years, has made it possible for scientists to go one step further in unraveling the story of the survival and evolution of this isolated population.
In June, the journal Cell published the latest results of an international team led by Sweden scientists that unveiled the detailed story of the final years of the long-haired mammoth in Siberia by comparing the genomes of mammoths from the wider continent and isolated on Wrangel Island over a 50,000-year scale. This new discovery not only challenges our understanding of the evolution of this isolated mammoth population and its small population, but also has important implications for today's conservation efforts of endangered species.
Specifically, the research team analyzed the genomes of 21 Siberian woolly mammoths, including 13 newly sequenced samples and eight samples that they had discovered and sequenced more than a year ago. The samples span a period of time, from the Late Pleistocene to the Holocene, including the isolation of mammoths on Wrangel Island; In terms of spatial span, it covers the northern hemisphere continent and Wrangel Island. One of the oldest genomic samples comes from a female Siberian mammoth that died about 52,300 years ago; The youngest specimens were male mammoths from Wrangel Island, who died more than 4,000 years ago.
The ivory remains of a Siberian woolly mammoth
The researchers used advanced ancient DNA sequencing technology and a series of bioinformatics analyses to assess the genomic diversity, inbreeding, genome-wide heterozygosity, homozygosity of homologous regions (ROHs), and other indicators of these samples.
Until then, it was more thought that abrupt climate change had led to the widespread extinction of the hairy mammoth population. In the latest study, scientists point out that mammoths did experience a "period of climate upheaval," but that the process probably began as early as about 20,000 years ago. Even during a period of rapid warming between about 14,700 and 12,900 years ago, scientists have found no evidence of any adverse effects of warming on the genome of mammoth populations. "In a period characterized by sudden changes in temperature, climate change has been suggested to be a possible cause of multiple extinctions of species at the end of the Ice Age, but we did not observe any genomic changes in mammoth inbreeding and genome-wide heterozygosity." The researchers said.
However, the team found that woolly mammoths isolated on Wrangel Island had a four-fold increase in genetic homology compared to before sea level rise. Increased genetic homology means that an individual's chromosomes are more likely to come from the same or similar ancestor. In other words, it was only after the last herd of woolly mammoths survived Wrangel Island and was cut off from the outside world that the genetic adverse effects became apparent.
The research team showed through genomic characterization and simulations that the woolly mammoth population experienced a severe "bottleneck" event after entering Wrangel Island and being "isolated". At its most severe, the total population of mammoths on Wrangel Island was less than 10 individuals.
But after the "life and death" of this race, something miraculous happened, and the mammoth population quickly recovered to the level of 200-300 individuals in the following 20 generations, and maintained a stable population size, inbreeding level, and genetic diversity for the next 6,000 years until it was completely extinct 4,000 years ago.
Moreover, unlike the population characteristics of the initial "bottleneck" period, the genomic characteristics of the population over time suggest that the breeding between mammoth populations has changed from very close inbreeding to more distant related pairings. This is also consistent with the slow decline in heterozygosity they found in the genome.
This conclusion suggests that genetic problems caused by inbreeding after surviving adversity on Wrangel Island may not have contributed to their extinction, and that their story is more complex than previously understood.
Wrangel Island covers an area of about 7,608 square kilometres, which is enough to provide enough living space and resources for these large animals.
In the 6,000 years since they were "isolated", while they have suffered population suppression due to inbreeding (increased mortality due to inbreeding and the defects it causes), inbreeding has also accelerated the clearance of "harmful" severe mutations to some extent.
In other words, two individuals with "harmful" severe genetic mutations often fail to produce offspring, or the progeny that reproduces is more likely to die after birth. From the perspective of the population as a whole, the surviving offspring are often less likely to carry "harmful" genetic mutations. So, for Wrangel Island mammoths, inbreeding doesn't seem like it's all really bad.
According to the paper's lead author, paleogeneticist Marianne Dehasque, "clearing harmful genetic mutations" could be a lengthy evolutionary process. And the "removal of harmful genetic mutations" from the mammoth population on Wrangel Island continued for more than 6,000 years.
This means that the woolly mammoth suffers from the negative effects of inbreeding while maintaining a stable population with the removal of "harmful" severe mutations, a process that has lasted for thousands of years. The discovery also disproved long-held speculation that isolated mammoth populations eventually became extinct on Wrangel Island due to inbreeding and genetic defects.
4,000 years ago, what happened suddenly?
As one of the most fascinating species of the last ice age, and a species that survived steadily on Wrangel Island for 6,000 years before suddenly becoming extinct, mammoths have long been regarded as a textbook model for studying small isolated populations. Exploring how a small population so close to us came to extinction on Earth will not only increase our understanding of the historical fate of woolly mammoths, but will also provide new genetic insights into the conservation of endangered species. Of course, these are only meanings, and human curiosity is the driving force for tireless exploration of the mystery of mammoths.
Combined with earlier research, it has been suggested that multiple genetic processes increase the risk of extinction in small populations. First, isolated small populations may gradually accumulate deleterious genetic mutations over time, leading to reduced adaptability, which is expected to lead to further population size reduction; Second, the phenomenon of inbreeding, which is commonly observed in small populations, is associated with its negative adaptive consequences and is therefore also thought to increase the risk of extinction; Third, a decrease in genome-wide heterozygosity may also translate into a loss of the population's adaptive potential, i.e., limiting the population's ability to adapt to environmental changes or resist pathogens.
Under these assumptions, it can be speculated that the genome of a small, isolated population will accelerate its decline over time. However, the paper, recently published in Cell, did not find any significant changes in the parameters of the above three genomes over a long period of time. Based on the results of the study, it is even shown that the woolly mammoth population on Wrangel Island recovered quickly after a "bottleneck" and remained stable during the subsequent 6,000 years of island isolation. The researchers even found that the recovered population was large enough for the mammoths to change their reproductive behavior to avoid reproduction with very close relatives, such as the closest first or second degree relatives, during the 6,000-year period of isolation.
Mammoth population size and diversity/inbreeding changes found in the study
However, the researchers' genetic mutation load analysis showed that while "highly deleterious" mutations due to inbreeding within the mammoth population have been removed, at the same time the frequency of "moderate" or "mild" deleterious mutations has increased. That is, in small populations, the gradual accumulation of "highly harmful" genetic mutations is eliminated, but the frequency of "mildly harmful" genetic mutations increases over time.
For example, in the woolly mammoth population on Wrangel Island, researchers found that the diversity of its major histocompatibility complex (MHC) decreased by 49.2% compared to the Late Pleistocene mammoth. The MHC gene plays a key role in the immune response, suggesting that the mammoth on Wrangel Island may be more susceptible to the disease. Compared to the Late Pleistocene mammoths, the Holocene mammoths had more than 40% less heterozygosity within the genome. As mentioned earlier, a decrease in genome-wide heterozygosity may limit a population's ability to adapt to environmental changes or resist pathogens.
Although the research team found evidence of genomic indicators in the Wrangel Island mammoth population, it does not appear to have affected the population so much that the mammoth population experienced a long-term negative growth rate. For example, comparisons with known human diseases have shown that the clearance process of some deleterious genetic mutations may disrupt genes that are important for the development of different senses, such as hearing and vision. However, this is unlikely to lead to the eventual extinction of mammoths. Similarly, mildly harmful genetic mutations, although they accumulate over time, do not become the main cause of the mammoth's eventual extinction.
And, most importantly, research data suggest that the extinction of the mammoths on Wrangel Island 4,000 years ago occurred rapidly. What was the reason behind the eventual extinction of mammoths on Wrangel Island? Why is it that the stable state that has lasted for 6,000 years suddenly does not work?
The research team also put forward some hypotheses and made further explorations. If the problem of inbreeding of the Wrangel Island mammoth population was not enough to lead to its eventual extinction, then what is the truth?
Could it be the impact of human activity? After all, over the past few centuries, human activity has brought many species around the world to the brink of extinction.
Although human civilization spread to many corners of the Earth's continent 4,000 years ago, available evidence suggests that the earliest human appearance on Wrangel Island dates back to about 3,600 years ago, almost four centuries after the mammoths disappeared from the island (although humans did coexist with mammoths and may have contributed to the disappearance of mammoths in continental areas during the Late Pleistocene, but there is currently no evidence that the same was true for mammoths on Wrangel Island).
Therefore, the researchers hypothesize that some other form of emergency, such as a disease outbreak or dramatic changes in climate and environment, combined with the fragile adaptive potential of the mammoth population, may have contributed to the eventual extinction of the mammoth on Wrangel Island.
Of course, the researchers also said that based on the analysis data, it could not be ruled out that the accumulation of moderate-impact genetic mutations over time span reached a tipping point that ultimately led to the unsustainability of the mammoth population. Or, to put it more conservatively, a combination of ecological and genetic processes may have contributed to the extinction of mammoths.
The latest insights provided by this study are of great significance for the current conservation of endangered populations, and will also have a broader impact on the field of conservation biology.
Someone is going to resurrect a mammoth?
Some study the death of mammoths, while others study resurrecting mammoths.
After watching the movie "Jurassic Park", it is better to understand why and how to resurrect mammoths, and we have already excavated relatively well-preserved mammoth remains in the Siberian permafrost, and this is a species that "just" became extinct 4,000 years ago, so resurrecting mammoths is more acceptable from an ecological or moral perspective than resurrecting dinosaurs.
When it comes to the main exponents who supported and promoted the resurrection of mammoths, we have to mention United States genetic engineer George · Church.
In 2008, George · Church first expressed the idea of resurrecting mammoths. Since mammoths and Asian elephants have 99.6% of the same DNA, the general idea of George · Church's team to resurrect mammoths is to first obtain enough ancient mammoth genes from frozen mammoths in the Arctic Circle, and then implant and splice enough key mammoth genes into the Asian elephant genome, and finally obtain functional embryos that can develop in Asian elephants, and use African elephants and Asian elephants as potential surrogacy targets. In this way, this shortly extinct creature can return to us.
In 2015, George · and his genetics team used CRISPR gene-editing tools to copy mammoth genes into the genome of Asian elephants. In the same year, his lab successfully integrated mammoth genes into the DNA of elephant skin cells.
In 2021, he co-founded a biotechnology company called Colosal Biosciences with United States entrepreneur Ben Lamm and raised $15 million in seed funding. They announced that the company's mission is to protect endangered animals through gene-editing technology and use these animals to reshape the Arctic ecosystem to combat climate change. And it is officially proposed to give birth to mammoth cubs in 2028.
Ben Lamm和乔治·丘奇
In March 2022, Colossal Biosciences raised $60 million in Series A funding. In January 2023, Colossal Biosciences closed a Series B funding round raising $150 million, valuing the company at more than $1 billion. Colossal Biosciences was also named to Time magazine's list of the 100 Most Influential Companies for 2023.
In March, Colossal Biosciences announced that they had successfully reprogrammed mature skin cells from Asian elephants into induced pluripotent stem cells (iPSCs) in the lab, arguably a major milestone in achieving the resurrection mammoth project.
The resurrection of mammoths seems to be a particularly sci-fi thing at first glance, but now it seems that maybe we will really have the opportunity to "see mammoths again" soon.