Nearly 100,000 years ago, a resolute group of Homo sapiens left Africa for the unknown. The impetus and timing of their exodus into the Arabian Peninsula remains controversial, but there's one thing paleoanthropologists know for sure: We weren't the only human species to have colonized Eurasia.
Genetic clues indicate that early humans and Neanderthals began to coexist and interbreed almost immediately after the great migration of Homo sapiens out of Africa. Their commingling lives on today in Asians and Europeans who carry the evidence of human and Neanderthal breeding in one to four percent of their genome. How, exactly, the genetic material of Neanderthals manifests in modern populations is the subject of scrupulous debate.
A new study published in the journal GENETICS proposes that harmful mutations in Neanderthals' genome not only made the hominin 40 percent less evolutionarily fit than modern humans, but also endowed some of us with that same genetic burden.
"Neanderthals are fascinating to geneticists because they provide an opportunity to study what happens when two groups of humans evolve independently for a long time—and then come back together," said lead author Kelley Harris in a statement. "Our results suggest that inheriting Neanderthal DNA came at a cost."
Previous studies that simulated the genetic load of Neanderthal mutations have estimated that early-generation human hybrids would have experienced a reduction in fitness of up to 94 percent compared to modern humans.
Geneticists know that several hominin species were interbreeding approximately 100,000 to 40,000 years ago, due to traces of DNA found in fossil remnants. Modern humans, Neanderthals, and an extinct species of human called Denisova hominin each encountered one another and left us with the evidence of such genetic admixture in their bones.
In the genome of non-African modern humans, specifically, glimpses of Neanderthal DNA are concentrated and uneven, the study notes. Genetic variants associated with Neanderthal DNA have been suggested by other researchers to influence traits such as skin color, addiction, metabolism, and allergies. However, the reasons behind why their genetic legacy appears only sporadically in the human genome have remained unclear until now.
The team of scientists from University of California, Berkeley and the University of Copenhagen theorized that weak natural selection in Neanderthals' small populations (as few as 1,000 individuals at a time over a period of 400,000 years) were responsible for allowing genetic mutations—both advantageous and deleterious—to persist over time. Neanderthals are believed to have had lower genetic diversity than any other living human population, which could signify the occurrence of a drastic bottleneck event that left the hominin with no option but to heavily interbreed.
Neanderthals likely avoided total extinction due to interbreeding, the study notes, by mating with other human species—like us. At one point, approximately 10 percent of modern humans' genome would have been inherited from Neanderthals. Using simulations based on current knowledge of Neanderthal genetics and evolution, the authors created models that show how mutations in their DNA would have built up and affected Homo sapiens once passed on through their offspring.
What their findings indicate is that Neanderthals carried a large number of genetic mutations associated with mild, yet harmful effects, such as diseases, and sterility in males. Combined, these mutations would have made the species 40 percent less likely to reproduce than modern humans.
To determine this percentage, the authors modeled the fitness effects of the same deleterious protein-coding mutations on sample groups of non-hybrid Neanderthals and modern humans. In a simulation of additive fitness effects, the median Neanderthal was found to have a genetic load of 0.63 compared to the median human. Given recessive fitness effects, the median Neanderthal fitness correlated to a genetic load of 0.39 compared to the median human. A disadvantage this significant would have been "incompatible" with Neanderthal survival, the study adds, if the species had continued to exist in isolation of genetic admixture with humans.
The study describes a selective tug-of-war that favored Neanderthal mutations in groups where they were beneficial, and stifled them where they were disadvantageous. Once sexually introduced to larger populations of Homo sapiens, however, most of these variants would have been subject to natural selection and lost.
Neanderthal mutations that persist in the DNA of non-African humans today are estimated to make those people 1 percent less evolutionarily fit than others without them, the study theorizes.
Harris and her colleagues also argued that Neanderthal mutations were more often than not deleterious, rather than adaptive for modern humans. Evidence of Neanderthal DNA found in the human genome, such as a blood disorder that causes excessive clotting, might have once been helpful to our ancestors, but is now considered adverse to our health.
Neanderthals disappeared from Earth 40,000 years ago, likely succumbing to a variety of factors including climate change and competition with modern humans. But their legacy lives on in some of us, and in the lessons we can learn from their extinction. The study's authors hope their research will contribute to the conservation of extant species facing population bottlenecks and a dangerous lack of genetic diversity.
"Genetic rescue is designed to move gene variants from an outbred population to an inbred population," said Harris. "Our results suggest managers must ensure that this movement only goes one way; otherwise harmful mutations from the inbred population may lower the fitness of the outbred group."