Home india-news What evolved between species, and what didn’t | Latest News India

What evolved between species, and what didn’t | Latest News India

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What evolved between species, and what didn’t | Latest News India

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New Delhi Two decades after a reference human genome was published for the first time, science has taken new steps towards investigating how the genome has evolved in relation to that of other mammals — discoveries that could answer key questions on life and evolution, perhaps even point to cures for diseases, including cancer. A large international collaboration, called the Zoonomia Project, looks at various aspects of the genetic evolution of 240 mammalian species.

Mammals constitute a very small fraction of animal species (estimates for the latter vary) but there are still nearly 6,000 kinds of mammals. (Representative)(Karen Carr/Smithsonian )
Mammals constitute a very small fraction of animal species (estimates for the latter vary) but there are still nearly 6,000 kinds of mammals. (Representative)(Karen Carr/Smithsonian )

What has changed in the genetic make-up of various mammals over 100 million years of evolution, and which parts of the genome have been conserved? What is the significance of the mutation in some regions, and the conservation of others, including for predisposition to disease?

The findings of 30 research teams on such questions have been published in 11 papers in a special edition of Science.

Why compare

Mammals constitute a very small fraction of animal species (estimates for the latter vary) but there are still nearly 6,000 kinds of mammals. The 240 species whose genomes were examined, therefore, represent only 4% of mammalian species, but they were diverse, representing 80% of mammalian families, the researchers said.

The idea is to go beyond human datasets to tackle human problems. The hypothesis is that if something is important for biological function, it will tend to be preserved during evolution. The papers thus look at DNA sequences that remain unchanged across many species over long periods of evolutionary time, as well as DNA sequences that suddenly start accumulating mutations in only one or a few lineages.

“It is key to study many species if you want to compare them to find regulatory elements that have persisted over 100 million years. The comparison is the key. Looking at individual genomes will only teach us about that species, but not about whole,” Kerstin Linblad-Toh, professor of comparative genomics at Sweden’s Uppsala University, and one of the two leaders of the international consortium, said in an email response.

The human genome contains some 20,000 genes that constitute the code for manufacturing all the proteins in the body. Beyond these are the so-called regulatory elements, which do not give rise to proteins themselves but contain instructions — where proteins are to be produced, when, and how much.

These regulatory elements, however, are more difficult to identify than the parts that give rise to proteins. That is what makes the analyses significant.

“The full data set of 240 species can find the regions that stay across all species (evolutionary constraint). When mapping disease genes, it is often hard to determine which mutation is the causative mutation. By comparing the mutations to constraint, we can see which are the most likely to be functional. This way we can start to understand the biology underlying disease. With a better understanding of the biology we can develop more specific treatment options,” Linblad-Toh said.

Balto, the dog

One of the 11 papers looks at the genome of the famous sled dog Balto, partly descended from the Siberian husky, who in 1925 helped save children in Nome, Alaska by delivering diphtheria serum to them during an outbreak. When other means of delivery were impossible in harsh winter conditions, sled dogs were engaged in the delivery in a relay from Anchorage to Nome, with Balto running the last leg.

Today, Balto’s remains are preserved in the Cleveland Museum of Natural History, a statue in his memory stands in New York’s Central Park, and his story has been adapted into an animation film, Balto (1995).

Using DNA from the preserved remains, the analysis looks at Balto’s evolution and compares his genome with that of other dogs. The researchers found that Balto and working sled dogs were genetically healthier than modern dog breeds, while Balto himself had more genetic diversity than both working sled dogs and modern dog breeds. Variants carried by Balto and his working contemporaries may have helped them survive the harsh conditions of 1920s Alaska, the paper said.

“We used two large comparative genomics datasets for the study — the first is the dog-referenced version of the Zoonomia alignment of 240 mammals and the second is a huge database of 682 genomes from dogs and wolves and other canids. We used Balto as a representative of his population, and identified genomic variants that were likely protein-altering, evolutionarily constrained, and likely common in his population of sled dogs,” Katherine L Moon, an evolutionary biologist with the University of California, Santa Cruz, said in an email response.

The variants identified tended to disrupt tissue development genes, things like joint formation, body weight, coordination and skin thickness. These are consistent with adaptation to the extreme environments in which early–20th century sled dogs worked, Moon said.

“Although the era of Balto and his contemporaries has passed, comparative genomics, supported by a growing collection of modern and past genomes, can provide insights into the selective pressures that shaped them,” the paper concludes.

Other findings

The researchers identified more than three million important regulatory elements in the human genome, about half of which were previously unknown. Conserved regions were found in these parts of the genome. The researchers hypothesised that when mutations happen in these regions, these could play a role in the origin of diseases.

Read: Chromosomal breakage caused by virus can lead to cancer: Study reveals

Indeed, the researchers found genetic variants that are likely to play roles in rare and common human diseases, including cancer. In one of the studies, researchers identified mutations in evolutionarily conserved positions of the genome in patients with medulloblastoma, a kind of tumour in the central nervous system. These mutations, the researchers feel, could be contributing to the growth of the brain tumours.

In other species, the researchers found genomic regions that give some animals a superior sense of smell and causes some species to hibernate. Another paper found that mammals had begun to diverge even before the Earth was hit by the asteroid that killed the dinosaurs, approximately 65 million years ago.



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