Our Homo sapiens ancestors shared the world with Neanderthals, Denisovans and other types of humans

When the first modern humans appeared in East Africa between 200,000 and 300,000 years ago, the world looked very different from today. Perhaps the biggest difference was that we – that is, people of our species, Homo sapiens – were just one of many types of humans (or hominins) that existed on Earth simultaneously.

From the well-known Neanderthals and more enigmatic Denisovans in Eurasia, to the diminutive “hobbit” Homo floresiensis on the island of Flores in Indonesia, to Homo naledi who lived in South Africa, multiple hominins abounded.

Then, between 30,000 and 40,000 years ago, all but one type of these hominids disappeared, and for the first time we were alone.

Until recently, one of the mysteries of human history was whether our ancestors interacted and bred with these other types of humans before their extinction. This fascinating question has been the subject of significant and often contentious debate among scientists for decades, because the data needed to answer this question simply did not exist. In fact, it seemed to many that the data would never exist.

Svante Pääbo, however, paid little attention to what people thought was or wasn’t possible. His perseverance in developing tools to extract, sequence, and interpret ancient DNA has resulted in the genomes of Neanderthals, Denisovans, and early modern humans who lived more than 45,000 years ago.

For developing this new field of paleogenomics, Pääbo was awarded the 2022 Nobel Prize in Physiology or Medicine. This honor is not only well-deserved recognition for Pääbo’s triumphs, but also for evolutionary genomics and the ideas that it can contribute to a more complete understanding of human health and disease.

Mixing and mating, revealed by DNA

Genetic studies of living people over the past few decades have revealed general outlines of human history. Our species originated in Africa, dispersed from that continent about 60,000 years ago, eventually spreading to almost every habitable place on Earth. Other types of humans existed as modern humans migrated across the world, but genetic data showed little evidence that modern humans mated with other hominins.

Over the past decade, however, the study of ancient DNA, recovered from fossils dating back around 400,000 years, has revealed startling new twists in human history.

For example, the Neanderthal genome provided the data needed to definitively show that humans and Neanderthals mated. Non-African peoples alive today inherited about 2% of their genomes from Neanderthal ancestors, through this type of interbreeding.

In one of the biggest surprises, when Pääbo and his colleagues sequenced ancient DNA obtained from a small finger bone fragment believed to be Neanderthal, it turned out to be a totally unknown type of human, now called Denisovans. Humans and Denisovans have also interbred, with the highest levels of Denisovan ancestry being present today – between 4% and 6% – among individuals of Oceanian ancestry.

Amazingly, ancient DNA from a 90,000-year-old woman has revealed she had a Neanderthal mother and a Denisovan father. Although there are still many unanswered questions, the picture that emerges from analyzes of ancient and modern DNA is that not only did multiple hominids overlap in time and space, but matings were relatively common. .

Archaic genes you carry today

Estimating the proportion of ancestry that modern individuals have from Neanderthals or Denisovans is certainly interesting. But ancestry proportions provide limited information about the consequences of these ancient matings.

For example, does DNA inherited from Neanderthals and Denisovans influence the biological functions that occur in our cells? Does this DNA influence traits like eye color or susceptibility to disease? Have DNA sequences from our evolutionary cousins ​​ever been beneficial, helping humans adapt to new environments?

To answer these questions, we need to identify the Neanderthal and Denisovan DNA fragments scattered throughout the genomes of modern individuals.

In 2014, my group and David Reich’s group independently published the first surviving maps of Neanderthal sequences in the DNA of modern humans. Today, about 40% of the Neanderthal genome has been recovered not by sequencing ancient DNA recovered from a fossil, but indirectly by reconstructing Neanderthal sequences that persist in the genomes of contemporary individuals.

Similarly, in 2016, my group and David Reich’s group published the first comprehensive catalogs of DNA sequences in modern individuals inherited from Denisovan ancestors. Surprisingly, when we analyzed the Denisovan sequences that persist in humans today, we found that they came from two distinct Denisovan populations, and thus at least two distinct waves of matings occurred between Denisovans and modern humans.

Analysis of Neanderthal and Denisovan DNA in modern humans reveals that part of their sequence was harmful and was quickly purged from human genomes. In fact, the initial fraction of Neanderthal ancestry among humans who lived around 45,000 years ago was around 10%. This amount declined rapidly over a small number of generations to the 2% seen in contemporary individuals.

The deletion of deleterious archaic sequences has also created large regions of the human genome that are significantly depleted in Neanderthal and Denisovan ancestry. These archaic hominin sequence deserts are interesting because they can help identify genetic changes that contribute to unique modern human traits, such as our ability for language, symbolic thought and culture, although there is some debate. on how unique these traits are to modern humans.

In contrast, there are also sequences inherited from Neanderthals and Denisovans that were advantageous and helped modern humans adapt to new environments as they dispersed out of Africa. Neanderthal versions of several genes related to the immune system reached high frequency in several non-African populations, which likely helped humans avoid exposure to new pathogens. Similarly, a version of the EPAS1 gene, which contributes to the high altitude adaptation of Tibetan populations, was inherited from the Denisovans.

It is also becoming clear that DNA sequences inherited from Neanderthal and Denisovan ancestors contribute to the burden of disease in individuals today. Neanderthal sequences have been shown to influence both susceptibility and protection against severe COVID-19. Archaic hominin sequences have also been shown to influence susceptibility to depression, type 2 diabetes, and celiac disease, among others. Ongoing studies will undoubtedly reveal more about the contribution of Neanderthal and Denisovan ancestry to human disease.

I was a graduate student when the Human Genome Project was winding down a little over twenty years ago. I was drawn to genetics because I found it fascinating that by analyzing the DNA of individuals today, one could uncover aspects of the history of a population that occurred ages ago. tens of thousands of years.

Today, I am equally fascinated by the stories contained in our DNA, and the work of Svante Pääbo and his colleagues has made it possible to tell these stories in a way that was simply not possible before.

This article is republished from The Conversation under a Creative Commons license. Read the original article.