human evolution

Natural selection is an ongoing process – our bodies are constantly mutating

Researchers have identified genetic variants that are less common in older people, suggesting natural selection continues to weed out disadvantageous traits.

Human evolution can seem like a phenomenon of the distant past that applies only to our ancestors living millions of years ago. But human evolution is ongoing. To evolve simply means that mutations – the accidental changes to genes that happen normally in the process of copying DNA – are becoming more or less common in the population over time.

These changes can happen by chance, because the individuals who reproduced happened to carry a particular mutation somewhat more often than individuals who did not have children. They can also happen because of natural selection, when carriers of a specific mutation are better able to survive, reproduce or tend to their family members – and therefore leave more descendants. Every biological adaptation, from the ability of humans to walk upright on two feet to flight in birds, ultimately traces back to natural selection acting on these minute changes, generation after generation.

So humans are definitely still evolving. The question is whether we are still adapting: are individuals who carry harmful mutations living less long, reproducing less – ultimately leaving fewer descendants? For instance, terrible eyesight may have been a major survival disadvantage living on the savanna, but with glasses and laser surgery, it is unlikely to prevent people from living a long life today. How commonly then are mutations under selection in contemporary humans?

Long time scale

Because adaptations involve tiny changes in the frequencies of mutations from generation to generation and their fortune plays out over tens to hundreds of thousands of years, they are incredibly hard to study directly – at least in long-lived organisms such as people.

So while there is overwhelming evidence for human evolution and unequivocal footprints of adaptation in the genome, rarely have scientists been able to directly observe natural selection operating in people. As a result, biologists still understand very little about the workings of natural selection in humans.

Indeed, one of the clearest footprints of a past adaptation in the human genome involves a mutation that permits milk to be digested in adulthood. This mutation in the lactase gene rapidly rose in frequency with the rise of dairy farming thousands of years ago, independently in multiple populations. It is the reason some people can drink milk as adults, whereas most remain lactose intolerant.

But even in this well-studied case, let alone for the rest of the genome, researchers do not know whether the mutation was beneficial for survival or for reproduction; whether the benefits were the same for both sexes, or across all ages; or whether the benefit depended on the environment (for instance, availability of other food sources). As pointed out by evolutionary biologist Richard Lewontin in the 1960s, to learn these properties of natural selection would require a massive study, in which genetic and genealogical information is obtained for hundreds of thousands of people.

Fifty years later, our group realised that this thought experiment is starting to become feasible. We sought large biomedical data sets that would let us learn about mutations that affect survival.

Gene frequency across age groups

Our basic idea was that mutations that lower the chance of survival should be present at lower frequency in older individuals. For example, if a mutation becomes harmful at the age of 60 years, people who carry it have a lower chance to survive past 60 – and the mutation should be less common among those who live longer than that.

We therefore looked for mutations that change in frequency with age among around 60,000 individuals from California (part of the GERA cohort) and around 150,000 from the UK Biobank. To avoid the complication that people whose ancestors lived in different places carry a somewhat different set of mutations, we focused on the largest group with shared ancestry within each study.

Across the genome, we found two variants that endanger survival. The first is a variant of the APOE gene, which is a well-known risk factor for Alzheimer’s disease. It drops in frequency beyond age 70. The second harmful variant we found is a mutation in the CHRNA3 gene. Associated with heavy smoking, this inherited mutation starts to decrease in frequency at middle age in men, because carriers of this mutation are less likely to survive longer.

Both deleterious variants only had an effect long after the typical ages of reproduction for both females and males. Biologists usually consider such mutations to not be under selection. After all, by late middle age, most people have already passed their genes on to whatever offspring they will have, so it seems like it might not matter how long they live beyond that point.

People who carry a variant of the APOE gene die at a higher rate and are less common among the old age categories. Mostafavi et al, PLOS Biology, CC BY
People who carry a variant of the APOE gene die at a higher rate and are less common among the old age categories. Mostafavi et al, PLOS Biology, CC BY

Why then would we only find two, when our study was large enough to detect any such variant, if common in the population? One possibility is that mutations that only imperil survival so late in life almost never arise. While that is possible, the genome is a large place, so that seems unlikely.

The other intriguing possibility is that natural selection prevents even late-acting variants from becoming common in the population by natural selection, if they have large enough effects. Why might that be? For one, men can father children in old age. Even if only a tiny fraction of them do so, it may be enough of an evolutionary fitness cost for selection to act on. Survival beyond the age of reproduction could also be beneficial for the survival of related individuals who carry the same mutations, most directly children. In other words, surviving past typical reproductive ages may be beneficial for humans after all.

Smokers who carry a mutation in the CHRNA3 gene tend to smoke more cigarettes per day and so are more exposed to the harmful effects of smoking. NeONBRAND on Unsplash, CC BY
Smokers who carry a mutation in the CHRNA3 gene tend to smoke more cigarettes per day and so are more exposed to the harmful effects of smoking. NeONBRAND on Unsplash, CC BY

Your mutations do influence your survival

In addition to examining one mutation at a time, we were also interested in considering sets of mutations that have all been shown to influence the same trait, and might have very subtle effects on survival individually. For example, researchers have identified approximately 700 common mutations that influence height, each contributing only millimeters. To this end, we considered tens to hundreds of mutations that shape variation in one of 42 traits.

We found genetic mutations linked to a number of diseases and metabolic traits that decrease survival rates: individuals who are genetically predisposed to have higher total cholesterol, LDL cholesterol, risk of heart disease, Body Mass Index, risk of asthma or lower HDL cholesterol tend to die younger than others.

Perhaps more surprisingly, we discovered that people who carry mutations that delay puberty or the age at which they have their first child tend to live longer. It was known from epidemiological studies that early puberty is associated with adverse effects later in life such as cancer and obesity. Our results indicate some of that effect is probably due to heritable factors.

So humans carry common mutations that affect their survival and natural selection appears to act on at least a subset, in some contemporary environments. But what is bad in one context may well not be in another; as one example, the CHRNA3 variant has an effect because people smoke. These are early days, however, and our findings offer only a first glimpse of what can soon be gleaned from millions of genomes, in combination with genealogical records. In future work, it will be important to study not only lifespan, but also the number of children and grandchildren individuals leave, as well as populations and environments worldwide.

Hakhamanesh Mostafavi, PhD Student in Biological Sciences, Columbia University; Joe Pickrell, Adjunct Assistant Professor of Biological Sciences, Columbia University and Molly Przeworski, Professor of Biological Sciences, Columbia University.

This article first appeared on The Conversation.

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“My body instantly craves chai and samosa”

German expats talk about adapting to India, and the surprising similarities between the two cultures.

The cultural similarities between Germany and India are well known, especially with regards to the language. Linguists believe that Sanskrit and German share the same Indo-Germanic heritage of languages. A quick comparison indeed holds up theory - ratha in Sanskrit (chariot) is rad in German, aksha (axle) in Sanskrit is achse in German and so on. Germans have long held a fascination for Indology and Sanskrit. While Max Müller is still admired for his translation of ancient Indian scriptures, other German intellectuals such as Goethe, Herder and Schlegel were deeply influenced by Kalidasa. His poetry is said to have informed Goethe’s plays, and inspired Schlegel to eventually introduce formal Indology in Germany. Beyond the arts and academia, Indian influences even found their way into German fast food! Indians would recognise the famous German curry powder as a modification of the Indian masala mix. It’s most popular application is the currywurst - fried sausage covered in curried ketchup.

It is no wonder then that German travellers in India find a quite a lot in common between the two cultures, even today. Some, especially those who’ve settled here, even confess to Indian culture growing on them with time. Isabelle, like most travellers, first came to India to explore the country’s rich heritage. She returned the following year as an exchange student, and a couple of years later found herself working for an Indian consultancy firm. When asked what prompted her to stay on, Isabelle said, “I love the market dynamics here, working here is so much fun. Anywhere else would seem boring compared to India.” Having cofounded a company, she eventually realised her entrepreneurial dream here and now resides in Goa with her husband.

Isabelle says there are several aspects of life in India that remind her of home. “How we interact with our everyday life is similar in both Germany and India. Separate house slippers to wear at home, the celebration of food and festivals, the importance of friendship…” She feels Germany and India share the same spirit especially in terms of festivities. “We love food and we love celebrating food. There is an entire countdown to Christmas. Every day there is some dinner or get-together,” much like how Indians excitedly countdown to Navratri or Diwali. Franziska, who was born in India to German parents, adds that both the countries exhibit the same kind of passion for their favourite sport. “In India, they support cricket like anything while in Germany it would be football.”

Having lived in India for almost a decade, Isabelle has also noticed some broad similarities in the way children are brought up in the two countries. “We have a saying in South Germany ‘Schaffe Schaffe Hausle baue’ that loosely translates to ‘work, work, work and build a house’. I found that parents here have a similar outlook…to teach their children to work hard. They feel that they’ve fulfilled their duty only once the children have moved out or gotten married. Also, my mother never let me leave the house without a big breakfast. It’s the same here.” The importance given to the care of the family is one similarity that came up again and again in conversations with all German expats.

While most people wouldn’t draw parallels between German and Indian discipline (or lack thereof), Germans married to Indians have found a way to bridge the gap. Take for example, Ilka, who thinks that the famed differences of discipline between the two cultures actually works to her marital advantage. She sees the difference as Germans being highly planning-oriented; while Indians are more flexible in their approach. Ilka and her husband balance each other out in several ways. She says, like most Germans, she too tends to get stressed when her plans don’t work out, but her husband calms her down.

Consequently, Ilka feels India is “so full of life. The social life here is more happening; people smile at you, bond over food and are much more relaxed.” Isabelle, too, can attest to Indians’ friendliness. When asked about an Indian characteristic that makes her feel most at home, she quickly answers “humour.” “Whether it’s a taxi driver or someone I’m meeting professionally, I’ve learnt that it’s easy to lighten the mood here by just cracking a few jokes. Indians love to laugh,” she adds.

Indeed, these Germans-who-never-left as just diehard Indophiles are more Indian than you’d guess at first, having even developed some classic Indian skills with time. Ilka assures us that her husband can’t bargain as well as she does, and that she can even drape a saree on her own.

Isabelle, meanwhile, feels some amount of Indianness has seeped into her because “whenever its raining, my body instantly craves chai and samosa”.

Like the long-settled German expats in India, the German airline, Lufthansa, too has incorporated some quintessential aspects of Indian culture in its service. Recognising the centuries-old cultural affinity between the two countries, Lufthansa now provides a rich experience of Indian hospitality to all flyers on board its flights to and from India. You can expect a greeting of Namaste by an all-Indian crew, Indian food, and popular Indian in-flight entertainment options. And as the video shows, India’s culture and hospitality have been internalized by Lufthansa to the extent that they are More Indian Than You Think. To experience Lufthansa’s hospitality on your next trip abroad, click here.


This article was produced by the Scroll marketing team on behalf of Lufthansa as part of their More Indian Than You Think initiative and not by the Scroll editorial team.