Science & Technology

What makes humans unique? Scientists compare genomes of 240 species to uncover secrets of mammalian evolution

Mammals diversified when continental landmasses began drifting apart, notes study

By Rohini Krishnamurthy
Published: Friday 28 April 2023
Mammals comprise roughly 6,500 living species and represent over 180 million years of genome evolution. Representative image: iStock.
Mammals comprise roughly 6,500 living species and represent over 180 million years of genome evolution. Representative image: iStock. Mammals comprise roughly 6,500 living species and represent over 180 million years of genome evolution. Representative image: iStock.

Scientists have analysed the DNA of 240 mammalian species to provide insights into human evolution. They compared the genomes of humans and other mammals to understand more about what makes humans unique.

The analyses, published in a series of 11 papers in journal Science on April 29, 2023, were conducted by more than 150 researchers from 50 institutions. These researchers are a part of the Zoonomia project, an international collaboration focussed on uncovering new ways of understanding mammalian evolution and humans.

Also read: ‘Changing climatic conditions induce vegetation changes, which shapes human evolution’

“The human genome was sequenced more than 20 years ago. Despite that, it has been hard to understand the functional elements in the genome,” Kerstin Lindblad-Toh, professor of comparative genomics at Uppsala University, Sweden, said in a press briefing.

The human genome contains more than 20,000 genes, she added. Some 10 per cent of the genes are functional. These include genes that code proteins (instructions in the gene are used to make proteins) or regulatory elements (DNA sequences that regulate how much of the instructions in the genes are converted into a functional protein).

The international team of researchers compared 240 mammalian species, representing only 4 per cent of all mammals. They also included 50 endangered species, Elinor Karlsson, director of the Vertebrate Genomics Group at the Broad Institute of Massachusetts Institute of Technology and Harvard, said at the briefing.

Mammals comprise roughly 6,500 living species and represent over 180 million years of genome evolution.

The analysis was based on the theory that if a region in the DNA is essential for biological function, it will be preserved. This means biologically important parts of DNA do not undergo too many mutations. The researchers saw that more than 100 million sites in the DNA show little to no changes across placental mammals.

The genome also contains neutral regions where changes are expected. And then, there are regions called accelerators, where many changes occur. “This suggests that a portion of the DNA has something to do with how the species adapts to its environment,” Karlsson said.

Mammalian evolution

One paper suggested that mammals diversified when continental landmasses began drifting apart. “The diversification accelerated when the dinosaurs went extinct (Cretaceous–Paleogene extinction event, 66 million years ago),” Karlsson said. 

Another paper looked at the link between enhancers and traits such as large brains relative to body size, solitary living, and vocal learning across 222 mammals. Enhancers are parts of the DNA whose role is to regulate how much of the instructions in the DNA are copied into RNA.

Humans have larger brains relative to the size of the body. The researchers identified multiple enhancer candidates associated with this feature. Many of these enhancers sit close to mutated versions of genes that are responsible for microcephaly (baby’s head is much smaller than expected) or macrocephaly ( overly large heads) in humans.

As for solitary living, the team identified enhancers near a gene implicated in separation anxiety. They also detected enhancers linked with the evolution of vocal learning ability. 

Also read: Human evolution didn’t stop at split from chimpanzees, 155 tiny new genes identified: Study

Another paper looked at stretches of DNA called human-accelerated regions (HAR), a part of the human genome. Human HARs possess an unexpected amount of differences compared to all other mammals, raising questions about their role in making humans unique.

HARs are the fastest-evolving regions in the human genome. “Typical HAR is 5-10 times different from chimpanzees. By comparison, chimpanzee HAR sequences are nearly identical to the HAR sequences of other mammals,” Katie Pollard, professor at the University of California, San Francisco, told Down To Earth.

Most HARs are enhancers. The new study revealed that more than 30 per cent of HARs are located near DNA regions bearing significant structural differences compared to chimpanzees.

DNA folds within cells like origami. This folding can decide the area where the enhancer winds up. Consider an enhancer close to a gene involved in controlling blood hormone levels. If the DNA folds, the enhancer could end up near a gene involved in another function.

“We realised that these human-specific structural changes may have created the right environment for HARs to evolve fast in the human ancestor after remaining almost the same over millions of years of mammal evolution,” said Kathleen Keough, first author of the study and former postdoctoral scholar in the Pollard lab at Gladstone.

Another experiment revealed that human HARs sat close to genes involved in brain development. They control genes that regulate embryonic development, including the formation of the brain, bones, and other tissues, Pollard explained. Many of these regulatory genes, she added, are linked to diseases, such as schizophrenia and atherosclerosis, that are unique to humans.

Still, understanding what makes humans unique is incomplete. “We know a great deal about humans, a little about primates. But we know surprisingly little about other species,” said Karlsson. This makes it hard to compare humans with other species, she explained.

Extinction risks

In another paper, researchers used sequencing information to predict which animals are at risk of extinction.

There is limited data on more than 20,000 species, making it difficult to assess their status, according to the International Union for Conservation of Nature.

Using machine learning, a type of artificial intelligence, the researchers concluded that species with smaller historical populations carry more damaging mutations and face extinction risk. 

Killer whales, for example, are more likely to be threatened, showed the genomic data, which also agreed with ecological surveys.

Karlsson stressed that ecological surveys of a species provide better information. But it is challenging to study when species live in remote areas. 

“Sequencing can be used as an initial assessment to determine if a species is at risk. It can help prioritise which species to put the additional resources on and confirm if it is at risk of extinction,” she noted.

However, climate change and habitat destruction are not going to be solved by genome sequencing, warned Lindblad-Toh.

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