Has human evolution stopped?

Image source: pixabay

Since human ancestors left Africa and migrated to all parts of the world, people in different regions quickly adapted to the local environment and evolved different characteristics, which seems to indicate that human evolution has accelerated recently. However, analysis of the human genome has allowed scientists to discover a completely different fact: natural selection occurs extremely slowly, and humans 5,000 years from now will still be the same as humans today.

By Jonathan Pritchard

Translation | Wang Chuanchao and Li Hui

Thousands of years ago, humans first arrived at the Qinghai-Tibet Plateau, which is more than 4,200 meters above sea level, after a long journey. At such high altitudes, the average oxygen content in the air is only about 60% of that at sea level, which can cause chronic altitude sickness, increase infant mortality, and be a severe test for their bodies. About 10 years ago, a series of studies discovered a gene variant that is common among Tibetans in China but rare in other populations. It can regulate the amount of red blood cells produced in Tibetans, which may help explain why Tibetans can adapt to the harsh living environment. This discovery provides a vivid example of how humans quickly adapted to new environments in the not-too-distant past. One study estimated that this beneficial variant spread to most Tibetans less than 3,000 years ago - in the long river of evolution, this is just a moment.

The findings in Tibetans seem to support the view that humans have undergone many such adaptations since they left Africa about 60,000 years ago (estimates range from 50,000 to 100,000 years ago). Admittedly, many of these adaptations have a “technological” component, such as the creation of clothing to protect against the cold. But in prehistoric times, technology alone was not enough to solve environmental problems such as widespread epidemics of infectious diseases and thin air in the mountains. In these cases, human adaptations could only be solved through genetic evolution rather than technology. Therefore, it is reasonable to expect that a comprehensive examination of the human genome will reveal many new genetic mutations that have recently spread to different populations due to natural selection—that is, the children of people with these mutations will be healthier and more reproductive than those of others.

In 2004, my colleagues and I began looking for the signatures of those far-reaching environmental challenges in the human genome. We wanted to understand how humans evolved after that global voyage tens of thousands of years ago. To what extent are the genetic differences between people in different parts of the world due to natural selection adapting to different environmental pressures? And how much of these genetic differences are due to other factors? Thanks to the continuous improvement of the technology for studying genetic variation, we are beginning to be able to answer these questions.

Studies have shown that there are almost no mutations in the human genome caused by very fast and intense natural selection processes. In contrast, most of the natural selection we see in the human genome seems to have taken tens of thousands of years to occur. One situation that seems to happen often is that a beneficial mutation spread throughout the human population long ago in response to local environmental pressures, and then as these people migrated to new territories, the mutation was also carried to further places. These ancient imprints of natural selection stayed in the genome for thousands of years without being changed by new environmental pressures, which shows that the process of natural selection is much slower than scientists thought. It seems that the rapid evolution of that important gene in Tibetans may be just a special case.

As an evolutionary biologist, I often ask whether humans are still evolving today. Of course we are. But the answer to how we are evolving is much more complicated. Classic natural selection works like this: a beneficial mutation spreads through the human population like wildfire. But our data show that this kind of natural selection has actually been rare in humans over the past 60,000 years. This kind of evolution usually requires some environmental pressures to remain unchanged for tens of thousands of years - which became uncommon once humans began to spread around the world and the rate of technological invention began to accelerate.

The above findings not only deepen our understanding of human evolution in recent times, but also give us a deeper understanding of what the future of humanity may be like. Currently, we are facing too many challenges, such as global climate change and frequent infectious diseases. Natural selection is too slow to provide us with much help. We can only rely on culture and technology.

Select Imprint

In the 20th century, it was extremely difficult for scientists to find genetic mutations that human ancestors produced in response to environmental changes because the tools needed to do this research did not exist. With the completion of human genome sequencing, more and more genetic mutations have been discovered by scientists, and this situation has changed fundamentally.

Overall, the genomes of any two people are extremely similar, with only about 1 difference in every 1,000 nucleotide pairs. The DNA site where one nucleotide pair is replaced by another is called a single nucleotide polymorphism (SNP), and the individual DNA fragments at each SNP site are called alleles. Since most sequences in the genome neither encode proteins nor regulate gene expression, many SNPs may not have a significant effect on individuals. However, if a SNP appears in a region that encodes proteins or regulates gene expression, it may affect the structure and function of a certain protein, or affect the location or output of the protein synthesis.

When natural selection particularly "favors" a certain allele, this gene will become more and more common as the population reproduces. Conversely, unfavored genes will become less and less common. If the environment continues to remain in this state, the beneficial allele will spread until everyone in the population carries it - at this point, the allele is considered to be fixed in the population. In theory, if a beneficial allele can give an individual a great survival advantage, the gene can be fixed in the population in just a few hundred years; on the contrary, if the advantage it brings is not so obvious, it will take thousands of years to stabilize in the population.

It would be ideal if we could extract DNA samples from ancient human remains to track how beneficial alleles changed over time when studying recent human evolution. However, DNA in ancient remains usually degrades rapidly, making it difficult to extract DNA samples from them. Therefore, we and many other scientists around the world have developed methods to look for traces of natural selection in the past by studying genetic variation in modern humans.

Image source: pixabay
One strategy is to analyze DNA data from different individuals in a population and search for fragments of SNP alleles that differ only slightly. When a new beneficial mutation spreads rapidly in a population, the DNA fragments adjacent to it on the chromosome will also spread with it, a process called "genetic hitchhiking." Over time, the beneficial allele will become more and more common in the population, while the neutral or nearly neutral alleles adjacent to it will also become more and more common - they have little effect on the structure and production of proteins, but will be inherited along with the beneficial allele. As a result, the number of SNP sites in the genomic region where the beneficial allele is located will be very small or even completely eliminated. This phenomenon is called selective sweep. When alleles spread under the action of natural selection, they will leave another completely different mark on the genome: when a population enters a new environment, if an existing allele can immediately provide them with great help, this gene will not necessarily cause the "genetic hitchhiking" phenomenon and can become very common in the population (but it will still be rare in other populations).

Several studies have found hundreds of clear signs of natural selection in the human genome over the past 60,000 years, since our ancestors left Africa. For a few of these signs, scientists already know what selection pressures they represent and what benefits alleles carrying these signs bring to humans.

In nomadic peoples of Europe, the Middle East, and East Asia, regions of the genome containing the gene for lactase, which breaks down lactose in dairy products, have clearly experienced intense natural selection. In most populations, infants are born with the ability to digest lactose, but after weaning, the lactase gene stops being expressed, so that people can no longer digest lactose as adults. In 2004, a research team at the Massachusetts Institute of Technology published an article in the American Journal of Human Genetics stating that they estimated that mutant forms of the lactase gene, which are still active in adults, became widespread among European nomads in just 5,000 to 10,000 years. In 2006, a research team led by Sarah Tishkoff, now at the University of Pennsylvania, reported in Nature Genetics that they had found evidence of rapid evolution of the lactase gene among East Asian nomads. These changes must have been an adaptation to new living conditions.

We can also see the imprint of selection in a series of genes that confer resistance to infectious diseases. Pardis Sabeti of Harvard University in the United States has found a gene that has only recently spread to most Yoruba people in Nigeria, the so-called LARGE gene. This is probably the result of the Yoruba people's response to Lassa fever (acute viral hemorrhagic fever disease) that has only recently appeared in the local area.

Slow evolution

These and a handful of other examples provide strong evidence that natural selection can rapidly promote the spread of beneficial alleles. However, for the remaining hundreds of candidate imprints, we don’t know what environmental conditions promoted the spread of these selected alleles, nor what effects carrying them would have. We and other scientists have analyzed that these hundreds of candidate imprints may represent at least several hundred rapid selective sweeps that occurred in the few human populations studied over the past 15,000 years. But in a newer study, my colleagues and I have found evidence that the vast majority of these imprints were not actually created by recent, rapid adaptations to local environments at all.

In collaboration with colleagues at Stanford University, we analyzed a large amount of SNP data from DNA samples of 1,000 people around the world. When we studied the geographic distribution of alleles with selective imprinting, we found that most of the apparent selective imprinting followed one of three distribution patterns: "out-of-Africa sweeping pattern," "West Eurasian sweeping pattern," and "East Asian sweeping pattern."

These purge patterns suggest something interesting: the migrations of human ancestors had a strong impact on the global distribution of beneficial alleles, while natural selection has done little to adjust these distributions to match modern environmental pressures.

Take, for example, a mutation in the gene SLC24A5, one of the most important genes responsible for light skin. Because it is an adaptation to reduced light intensity, one might expect that the frequency of this mutation in a population would increase with latitude, with a similar distribution in northern Asians and northern Europeans. Instead, we see a “West Eurasian sweep pattern”: the mutation and its hitchhiker DNA are common in populations from Pakistan to France, but are almost absent in East Asians, even in northeastern Asia. This distribution pattern suggests that the beneficial mutation arose in West Eurasians and was carried to the region where they live after their common ancestor split from East Asians. So the initial widespread appearance of the SLC24A5 gene was the result of natural selection, but which populations today have the gene and which do not is determined in part by early human history (light skin in East Asians is caused by other genetic variants).

A closer look at the imprinting and other data revealed another odd pattern. Some alleles vary widely in commonness among populations, with nearly all Asians having them, for example, and no Africans having them. One might expect natural selection to have a strong hitchhiking effect as it promoted the rapid spread of these new alleles. But the vast majority of these genes showed no such effect. Instead, they seemed to have spread gradually over the 60,000 years since our ancestors left Africa.

Given these findings, my colleagues and I argue that classic selective sweeps—where a new advantageous mutation becomes fixed rapidly in a population under the influence of natural selection—actually occurred only rarely after our ancestors set out on their journey around the world. We speculate that natural selection would have acted relatively weakly on individual alleles, and thus would have driven the spread of genes only slowly. As a result, most alleles would have spread through the population under selective pressure only if environmental pressures persisted for tens of thousands of years.

Continue to evolve?

Our conclusions seem paradoxical: If it really takes 50,000 years for a useful allele to become prevalent in a population, rather than 5,000 years, then how can humans adapt so quickly to new environments? Although our best-understood adaptations result from single-gene mutations, the vast majority of adaptations probably do not arise this way, but rather from a few genetic variants that have modest effects on thousands or tens of thousands of related genes in the genome.

When natural selection modulates human height, it does so over a wide range, changing the frequencies of hundreds or even thousands of different alleles. Take the Pygmies, who live in the rainforests of Africa, Southeast Asia, and South America, where short stature is more adaptable to nutrient-poor environments. If the prevalence of each "short stature gene" could increase by only 10%, most Pygmies would gain more of these genes in a short period of time, and the group as a whole would become shorter. Even if the overall height of the Pygmies was subject to very strong selection pressure, the selection pressure on each "height gene" could still be weak. Because of this, polygenic adaptations don't leave the selection marks we often see in our studies on the genome.

Are humans still evolving? It is difficult to find evidence of natural selection acting on humans today. But it is not difficult to imagine what human traits might be affected by natural selection. In developing countries, infectious diseases such as malaria and AIDS exert strong selection pressure on the people of these countries. Known gene mutations that give local people some resistance to these diseases may be experiencing strong selection, because people with these mutations are more likely to survive and reproduce more offspring than those without such mutations.

In developed countries, where few people die before adulthood, the genes that may be under the greatest selection pressure are those that influence how many children people have. In theory, any aspect of fertility or reproductive behavior that is affected by genetic mutations could be a target for natural selection.

However, compared with the rate of change in culture, technology, and, of course, the Earth's environment, most human genetic traits change extremely slowly. Moreover, large adaptive shifts require the environment to remain unchanged for tens of millions of years. Thus, 5,000 years from now, the environment in which humans live will undoubtedly change greatly, but unless the genome has undergone large-scale artificial modification, humans will probably remain the same as they are today.

Global Science