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  • Decoding the Genomes of the Largest and Smallest Mammals

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    Size doesn’t matter when it comes to genome sequencing in the animal kingdom, as a team of researchers at the Morgridge Institute for Research recently illustrated when assembling the sequences for two new reference genomes—one from the world’s largest mammal and one from one of the smallest. (Image Credit: University of Wisconsin–Madison)



    In a recent collaborative effort led by the Morgridge Institute for Research, scientists have successfully assembled the reference genomes for two significantly disparate members of the animal kingdom: the blue whale, the largest mammal, and the Etruscan shrew, one of the smallest. This achievement, published in Molecular Biology and Evolution and Scientific Data respectively, underscores the fact that in terms of genome sequencing, size does not dictate complexity or challenge.

    Deciphering Life's Blueprint
    The research undertaken by the team, particularly noted by Yury Bukhman, a computational biologist at the Morgridge Institute, highlights the foundational importance of understanding an organism's genome. Bukhman noted, "The genome is a blueprint of an organism. In order to manipulate cell cultures or measure things like gene expression, you need to know the genome of the species—it makes more research
    possible."


    The selection of the blue whale and Etruscan shrew for genome sequencing stems from a broader investigation into the biological mechanisms of developmental timing, an area previously explored by James Thomson of Morgridge. The question of why organisms of larger sizes require longer developmental periods compared to their smaller counterparts remains largely unanswered, yet it is crucial for fundamental biological understanding and practical applications in regenerative medicine.

    Moreover, the comparative study of these genomes might illuminate the enigmatic Peto’s paradox. This phenomenon suggests that larger mammals, despite undergoing more cell divisions, exhibit lower cancer rates than their smaller counterparts. Conversely, insights into the Etruscan shrew's genome could pave new paths in metabolic research, given the creature's high energy requirements due to its fast metabolic rate and small size.

    Technological Foundations
    The success of these genomic projects can be attributed to cutting-edge sequencing technologies. Traditional short-read sequencing techniques, which generate brief DNA sequences, often result in fragmented and incomplete genomes. In contrast, the Morgridge team employed long-read sequencing, producing reads of approximately 10,000 base pairs in length, allowing them to obtain longer contiguous sequences, or contigs, and reduced gaps.

    Further refinement was achieved through optical mapping and Hi-C technologies, which organize these long sequences into scaffolds, potentially encompassing entire chromosomes. This methodological innovation offers a more detailed and accurate representation of the genome, facilitating deeper biological insights.

    Conservation through Genomics
    An interesting discovery from the blue whale genome sequencing was a significant burst of segmental duplications in the recent past, a phenomenon not as prevalent in the Etruscan shrew genome. These duplications, particularly abundant in comparison to other cetaceans like the bottlenose dolphin and the vaquita, can offer insights into evolutionary processes and functional genomics. For instance, the identification of genes encoding the protein metallothionein in blue whales, which plays a role in mitigating heavy metal toxicity, illustrates the genome's potential to illuminate adaptive mechanisms in large marine mammals.

    The conservation implications of these genomic mappings are profound, especially for species like the blue whale, which has faced near extinction in the past. "The blue whale genome is highly heterozygous, there's still a lot of genetic diversity, which has important implications for conservation," Bukhman notes, highlighting the utility of genomic data in understanding and preserving biodiversity.

    While the focus on the Etruscan shrew's genome was less intensive than that on the blue whale, the team still had notable discoveries. “We found that there are relatively few segmental duplications in the shrew genome,” Bukhman stated. He stressed that this result does not necessarily correlate to the smaller size of the shrew. “While shrews belong to a different mammalian order, some similarly small rodents have lots of segmental duplications, and the house mouse is kind of a champion in that sense that it has the most. So, it's not a matter of size.”

    The endeavor to sequence the genomes of these two mammals involved a comprehensive and collaborative effort, part of the larger Vertebrate Genomes Project aimed at assembling high-quality reference genomes for all living vertebrate species. This initiative underscores the collective push toward refining our understanding of genetic blueprints across the animal kingdom, thereby enhancing our capacity to address pressing biological questions and challenges in conservation and medicine.

    Original Publications
    • Bukhman, Y. V., Morin, P. A., Meyer, S., Chu, L. F., Jacobsen, J. K., Antosiewicz-Bourget, J., Mamott, D., Gonzales, M., Argus, C., Bolin, J., Berres, M. E., Fedrigo, O., Steill, J., Swanson, S. A., Jiang, P., Rhie, A., Formenti, G., Phillippy, A. M., Harris, R. S., Wood, J. M. D., … Stewart, R. (2024). A high-quality blue whale genome, segmental duplications, and historical demography. Molecular biology and evolution, 41(3), msae036. Advance online publication. https://doi.org/10.1093/molbev/msae036
    • Bukhman, Y. V., Meyer, S., Chu, L. F., Abueg, L., Antosiewicz-Bourget, J., Balacco, J., Brecht, M., Dinatale, E., Fedrigo, O., Formenti, G., Fungtammasan, A., Giri, S. J., Hiller, M., Howe, K., Kihara, D., Mamott, D., Mountcastle, J., Pelan, S., Rabbani, K., Sims, Y., … Stewart, R. (2024). Chromosome level genome assembly of the Etruscan shrew Suncus etruscus. Scientific data, 11(1), 176. https://doi.org/10.1038/s41597-024-03011-x

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