Kerstin Lindblad-Toh, a Comparative Genomics Professor at Uppsala University and co-leader of a global team of scientists, states, "The 11 pieces we currently release in Science offer a vast quantity of insights into the workings and progress of mammalian genomes. Additionally, we have generated information that will be valuable for evolutionary investigations and healthcare studies for an extended period."

A collaborative effort between Uppsala University and the Broad Institute, involving over 30 research teams, has conducted a comprehensive survey and analysis of 240 mammalian genomes. The findings, which have been published in 11 articles in Science, elucidate the evolutionary trajectory of mammalian genomes, including that of humans.

Roughly 20,000 genes are present in the human genome, which encode the blueprint for synthesizing all the body's proteins. Moreover, the genome encodes guidelines that dictate the site, timing, and quantity of protein synthesis. While protein-coding regions are easy to identify, regulatory elements that govern gene expression are more challenging to locate. Nevertheless, by studying numerous mammalian genomes, it is possible to determine which regions of the genome are functionally significant.

The researchers involved in the publications in Science hypothesized that if a genomic location remains conserved across 100 million years of evolution, it is likely to serve a function in all mammals. For the first time, they tested this hypothesis extensively by conducting a comprehensive survey and systematic comparison of the genomes of 240 mammals. The researchers were able to pinpoint regions of the human genome that lacked prior functional characterization, likely comprising regulatory elements crucial for proper genome function. Mutations in these regions may contribute significantly to disease onset or unique traits in mammalian species.

The researchers successfully identified over three million significant regulatory elements in the human genome, half of which were previously undiscovered. Moreover, they determined that a minimum of 10 percent of the genome performs a function, which is ten times more than the approximately one percent that encodes proteins.

The study included 240 diverse mammalian species, varying greatly in characteristics such as olfactory acuity or brain size. The researchers identified genome regions that contributed to species-specific traits, such as superior olfactory abilities or hibernation.

Matthew Christmas, a researcher and co-first author of one of the articles investigating the genome's function and its role in diverse species' unique traits, comments, "It's thrilling to finally have a comprehensive understanding of which mutations have influenced the emergence of distinct traits in such divergent mammals."

One of the studies reveals that mammalian evolution had already commenced and begun diverging well before the asteroid impact that caused the extinction of dinosaurs, occurring approximately 65 million years ago.

Professor Lindblad-Toh highlights that their findings also offer critical insights into the vulnerability of mammalian species to extinction, based on the extent of genomic variation. This information could form the groundwork for devising conservation strategies that can safeguard species survival.

The newfound insights also facilitate a deeper understanding of disease onset by connecting evolutionarily conserved genomic locations to identified medical conditions. This association can be established for all species, including humans, providing researchers with a valuable resource for investigating the mechanisms underlying the development of diseases.

Jennifer Meadows, a researcher and co-first author of the second article focused on leveraging the project's data to gain insights into disease, explains that their analyses of 240 mammalian genomes offer a more profound understanding of the genome's regulatory signals. They calibrated their findings on positions known to be associated with medical conditions, enabling the identification of additional positions that could be prioritized for studying neurological traits like schizophrenia, as well as immune conditions such as asthma or eczema.

Comparing the genome of healthy individuals with that of people affected by a disease can provide insights into which mutations contribute to the onset of the condition. However, while this approach can help identify regions of the genome that are potentially significant for the disease, it does not provide definitive knowledge about the specific mutation that causes the disease.

Kerstin Lindblad-Toh explains that a considerable portion of the mutations associated with common diseases, such as diabetes and obsessive-compulsive disorder, are located in non-coding regions of the genome, which play a role in gene regulation. By providing insights into the genome's regulatory signals, the project's studies can facilitate the identification of mutations that contribute to the onset of diseases and enhance our understanding of the underlying mechanisms.

In addition to investigating the evolution and function of mammalian genomes, the researchers also examined the cancer medulloblastoma, a malignant brain tumour that predominantly affects children. Despite recent advances in treatment, not all children with medulloblastoma can be cured, and survivors often suffer from long-term side effects resulting from the aggressive therapy.

It is worth noting that Karin Forsberg-Nilsson did not lead the cancer part of the study, but rather the stem cell research group at Uppsala University. The cancer research part of the study was led by Scott L. Pomeroy and David A. Louis, both affiliated with the Broad Institute of MIT and Harvard. (PB/Newswise)