Tollis led a\nteam of scientists from Arizona State University, the University of Groningen\nin the Netherlands, the Center for Coastal Studies in Massachusetts and nine\nother institutions worldwide to study potential cancer suppression mechanisms\nin cetaceans, the mammalian group that includes whales, dolphins and porpoises.\nTheir findings, which picked apart the genome of the humpback whale, as well as\nthe genomes of nine other cetaceans, in order to determine how their cancer defenses\nare so effective, were published today in Molecular Biology and Evolution<\/a><\/em>.<\/p>\n\n\n\n The study found\nthat nature has beaten cancer in countless ways across the tree of life, Tollis\nsaid, and researchers can use that information to help find potential new\ntargets for preventing cancer in humans, like using the whale version of a\nprotein that can stop cell proliferation to develop drugs that shrink tumors in\nhumans.<\/p>\n\n\n\n \u201cOur goal is not only to get\nnature to inform us about better cancer therapies, but to give the public a new\nperspective of cancer,\u201d Tollis said. \u201cThe fact that whales and elephants\nevolved to beat cancer, and that dinosaurs suffered from it as well, suggests\nthat cancer has been a selective pressure across many millions of years of\nevolution, and it has always been with us. Our hope is that this may change\npeople\u2019s relationship with the disease, which can be painful and personal. It\nalso helps provide even better appreciation for biodiversity. In our current\nsixth mass extinction, we need all the reasons for conservation that we can\nget.\u201d<\/p>\n\n\n\n At its most basic, cancer occurs when body cells divide and mutate. Cell division is normal in living creatures, as are body cell, or somatic, mutations. Most of the time, somatic mutations are either harmless or the body is able to fix those mutations. When it doesn\u2019t, that can lead to cancer.<\/p>\n\n\n\n Beyond that foundation, cancer gets much more complicated. For all of the research being done on all types of cancer and all types of organisms, there are still more questions than answers. However, age and body size are well-known risk factors in people. Tollis said one explanation for this is that cancer risk overall is a function of the number of cell divisions that occur over the lifetime of an organism. <\/p>\n\n\n\n \u201cThis is driven by somatic evolution\u2014genetic changes that occur when body cells copy their genomes, divide and produce daughter cells,\u201d he said. \u201cThe longer you live, the more cell divisions you have and the higher chance that a cancer-causing mutation will occur in the genome of the descendent cells. Similarly, larger individuals are made of more cells, which also increases the chance of cancer-causing mutations.\u201d<\/p>\n\n\n\n Knowing this, it\u2019s worth\nlooking at whether whales, which live longer than most mammals on the planet\nand have a much higher percentage of body fat, are more likely to develop\ncancer. They aren\u2019t. This phenomenon, known as Peto\u2019s Paradox, is what Tollis\nand his team studied. How do whales defy these well-known risk factors? <\/p>\n\n\n\n The team worked under a federal research permit to obtain skin samples from an adult female humpback whale off the coast of Massachusetts. This whale, named Salt, is well-known to researchers and whale watchers alike. She was cataloged by the Center for Coastal Studies in the mid-1970s and selected for this study because her life history is among the most well-documented of any individual humpback whale. The team sequenced and assembled Salt\u2019s genome, which requires extracting DNA from skin tissue, fractioning it into smaller bits and putting it through a DNA sequencer that produces almost 2 billion short sequences. Then they put those sequences back together into a genome assembly that spans about 2.7 billion base pairs. (By contrast, the human genome is about 3.1 billion base pairs long.) They also sequenced RNA, which helps in the process of finding the precise coordinates where genes lie in the genome.<\/p>\n\n\n\n Tollis and his team\nthen compared the humpback whale genome to those of other mammals including\nother ocean giants like the blue whale, fin whale, bowhead whale and sperm\nwhale. They expected to see a lot of differences, but also a few similarities, particularly\nwith the parts of the genome that perform important functions. They also looked\nfor parts of the genome that had evolved to help whales adapt to their\nenvironment. <\/p>\n\n\n\n What they found was\nthat some parts of the whale genome have evolved faster than in other mammals.\nThese parts of the whale genome contain genes that control the cell cycle, cell\nproliferation and DNA repair, which are essential for normal cell function. In\nhuman cancers, many of these genes are mutated. The whale genome also evolved many\nduplications in tumor suppressor genes. <\/p>\n\n\n\n \u201cNature is showing us that these changes to cancer genes are compatible with life. The next questions are, which of these changes is preventing cancer, and can we translate those discoveries into preventing cancer in humans?\u201d said Carlo Maley, a cancer evolutionary biologist from ASU\u2019s Biodesign Institute<\/a> and one of the two senior authors, who started this project in 2011 with Per Palsb\u00f8ll, a marine mammal conservation geneticist from the Groningen Institute for Evolutionary Life Sciences<\/a> at University of Groningen, in collaboration with Jooke Robbins from the Center for Coastal Studies<\/a>. <\/p>\n\n\n\n \u201cThis suggests\nthat whales are unique among mammals in that in order to evolve their gigantic\nsizes, these important \u2018housekeeping\u2019 genes, that are evolutionarily conserved\nand normally prevent cancer, had to keep up in order to maintain the species\u2019\nfitness,\u201d Tollis said. \u201cWe also found that despite these cancer-related parts\nof whale genomes evolving faster than other mammals, on average whales have\naccumulated far fewer DNA mutations in their genomes over time compared to\nother mammals, which suggests they have slower mutation rates.\u201d <\/p>\n\n\n\n This slow rate\nof change may also limit whales\u2019 exposure to cancer-causing somatic mutations.<\/p>\n\n\n\n This study\nbuilds on research that the ASU team has done finding lower rates of cancer in\nelephants, another mammal that is large and can live a long time but doesn\u2019t\nhave much in common genetically with whales. Both species arrived at the same\nresult\u2014cancer suppression\u2014through different mechanisms. The same is likely true\nof extinct giant dinosaurs; although scientists have found evidence of cancer\nin dinosaur fossils, this group of organisms includes the largest animals ever\nto walk the earth and thus they probably had efficient cancer suppression as\nwell.<\/p>\n\n\n\n Next steps for\nTollis and his team will be to better understand the cancer suppression\nphenotype using experiments with whale cell lines, which will provide important\nfunctional validation of the team\u2019s genomic results. That will be the first\nstep in generating whale-derived human cancer drugs. They also are looking at\nother animals, such as bats, tortoises and crocodilians, to see how these\nvaried long-lived species suppress cancer. The humpback whale genome also will serve\nas the basis for studies by other team members on whale mutation rates and\nother adaptations taking advantage of a collection of the 9,000-plus DNA samples\ncollected from free-ranging humpback whales curated by Palsb\u00f8ll\u2019s team.<\/p>\n\n\n\n This research is\nsupported by the Arizona Cancer Evolution Center, which is funded through a\nfive-year grant from the National Institutes of Health, with additional funding\nby the University of Groningen.<\/p>\n\n\n\nWhy whales?<\/strong><\/h4>\n\n\n\n
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Methods and conclusions<\/strong><\/h4>\n\n\n\n
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Heidi Toth | NAU Communications
(928) 523-8737 | heidi.toth@nau.edu<\/a><\/p>\n<\/div><\/div>\n","protected":false},"excerpt":{"rendered":"