{"556431":{"#nid":"556431","#data":{"type":"news","title":"Insights on Sex and Death from a Mutant Roundworm","body":[{"value":"\u003Cp\u003EIn tough times, humans aren\u2019t the only species that think twice about having children.\u0026nbsp; Consider roundworm strain LSJ2.\u003C\/p\u003E\u003Cp\u003EThough it can\u2019t think \u2013 much less think twice -- about anything, the laboratory worm underwent a surprising mutation that made it prioritize the survival of adults over creating abundant offspring.\u0026nbsp; Researchers noticed the sweeping change in behavior, and the mutation, after LSJ2 had faced hardship for 50 years.\u003C\/p\u003E\u003Cp\u003ESuch so-called life history trade-offs have been described in many living things from mice to elephants, but now, for the first known time, researchers at the Georgia Institute of Technology have pinned some to a specific mutation.\u003C\/p\u003E\u003Cp\u003E\u201cThis is a great hint at how life history trade-offs could be regulated genetically,\u201d said lead researcher Patrick McGrath, an assistant professor in Georgia Tech\u2019s School of Biological Sciences.\u003C\/p\u003E\u003Cp\u003EThe researchers confirmed the link in LSJ2, a strain of the \u003Cem\u003EC. elegans\u003C\/em\u003E species, by duplicating the mutation in another strain, which reproduced the mutation\u2019s effects to a very high degree.\u003C\/p\u003E\u003Cp\u003EThe researchers published their results \u003Ca href=\u0022http:\/\/journals.plos.org\/plosgenetics\/article?id=10.1371\/journal.pgen.1006219\u0022 target=\u0022_blank\u0022\u003Ein the journal PLOS Genetics\u003C\/a\u003E on Thursday, July 28, 2016.\u0026nbsp; Their work has been funded by the National Institutes of Health and the Ellison Medical Foundation.\u003C\/p\u003E\u003Ch4\u003ESnowball to avalanche\u003C\/h4\u003E\u003Cp\u003EThe mutation in the LSJ2 strain amounted to a small deletion in its DNA.\u0026nbsp; As a result, a large protein changed by a meager 10 of its roughly 3,000 amino acids.\u003C\/p\u003E\u003Cp\u003EBut that triggered a huge behavioral overhaul that boosted lifespan and slowed down reproduction.\u0026nbsp; The contrast between the minor genetic tweak and its transformative ramifications might compare well with a toddler knocking loose an avalanche with a snowball.\u003C\/p\u003E\u003Cp\u003EThe new discovery also has a tangential connection to human genetics.\u0026nbsp; The roundworm shares with us the NURF-1 gene, on which the mutation occurred.\u0026nbsp; And an associated human protein is involved in, among other things, reproduction.\u003C\/p\u003E\u003Ch4\u003EEvolve faster, please\u003C\/h4\u003E\u003Cp\u003EAll at once, LSJ2 did a lot of peculiar things, and that got the attention of McGrath and his team. And that\u2019s what the lab roundworms are there for.\u003C\/p\u003E\u003Cp\u003ESince 1951, generations of scientists have been speeding up the evolution of lab-bound \u003Cem\u003EC. elegans\u003C\/em\u003E by forcing the microscopic species of roundworms to adapt to new, mostly stressful, conditions.\u0026nbsp; Then, when researchers have noticed changes, they\u2019ve worked to trace them to the animals\u2019 genes.\u003C\/p\u003E\u003Cp\u003EMcGrath points to a thin, glass slide standing vertically under a light with tubules of fluid connected to it.\u0026nbsp; Inside the slide, is a different lab strain of \u003Cem\u003EC. elegans\u003C\/em\u003E.\u003C\/p\u003E\u003Cp\u003E\u201cWe\u2019re raising those in fluid with gravity pulling them down to see if mutations will give them the ability to swim,\u201d McGrath said.\u003C\/p\u003E\u003Ch4\u003E50 years of bread and water\u003C\/h4\u003E\u003Cp\u003EIn the case of LSJ2, researchers came up with a different challenge to accelerate its evolution. They fed it bland food for 50 years.\u003C\/p\u003E\u003Cp\u003E\u201cIt\u2019s a diet of watery soy extract with some beef liver extract,\u201d said Wen Xu, a graduate student who researches with McGrath.\u0026nbsp; Sounds yucky enough to humans, but to the roundworm, it\u0027s worse. It equates to a regimen of bread and water.\u003C\/p\u003E\u003Cp\u003EMutations eventually took hold to promote LSJ2\u2019s survival in the scanty broth, and they were head-turning.\u003C\/p\u003E\u003Ch4\u003EFewer kids, less sleep\u003C\/h4\u003E\u003Cp\u003E\u201cThe stark thing that we noticed first was the propensity to no longer enter the state called dauer,\u201d McGrath said.\u0026nbsp; It\u2019s a kind of hyper-hibernation.\u0026nbsp; \u201cDauer is something most \u003Cem\u003EC. elegans\u003C\/em\u003E do to extend their lives, but LSJ2 did not.\u0026nbsp; And it lived longer in spite of it.\u201d\u003C\/p\u003E\u003Cp\u003EThen the list of anomalies grew, and grew.\u003C\/p\u003E\u003Cp\u003E\u201cWe found that almost everything was affected \u2013 when they started reproducing, how many offspring they made, how long they lived,\u201d McGrath said.\u0026nbsp; Some even survived exposure to drugs and heavy metals.\u003C\/p\u003E\u003Cp\u003E\u201cEventually we realized that the worms were prioritizing individual survival over reproductive rate.\u201d\u003C\/p\u003E\u003Ch4\u003EMutation sleuthing\u003C\/h4\u003E\u003Cp\u003EIn many species, sex dries up when food is scarce, resulting in fewer progeny to compete for it.\u0026nbsp; In addition, many organisms are well-equipped to manage their energies to survive dearth.\u003C\/p\u003E\u003Cp\u003EBut \u003Cem\u003EC. elegans\u003C\/em\u003E LSJ2 had to mutate into those abilities, and so many mutation-based behavioral changes all at once is uncommon.\u003C\/p\u003E\u003Cp\u003E\u201cWhat you usually find is mutations that play narrow, very specific roles,\u201d McGrath said.\u0026nbsp; \u201cThey only affect egg laying, or they only affect life span, or they only affect dauer formation.\u0022\u003C\/p\u003E\u003Cp\u003EMcGrath and Xu went sleuthing for DNA alterations by mapping quantitative trait loci, which matches up changes in characteristics to genetic changes.\u0026nbsp; They dug in for a long investigation, anticipating multiple suspects among LSJ2\u2019s many mutations.\u003C\/p\u003E\u003Cp\u003E\u201cThere were hundreds of genetic differences between roundworm strain LSJ2 and the one we were comparing it to,\u201d McGrath said.\u003C\/p\u003E\u003Ch4\u003E\u2018Smoking gun\u2019\u003C\/h4\u003E\u003Cp\u003EThe comparison laboratory strain is called N2, and it has led a pampered existence with a diet of \u003Cem\u003EE. coli\u003C\/em\u003E -- optimal food for \u003Cem\u003EC. elegans\u003C\/em\u003E.\u0026nbsp; (Both the \u003Cem\u003EE. coli\u003C\/em\u003E and the roundworms are strains that are not harmful to humans.)\u003C\/p\u003E\u003Cp\u003ESo, N2 hadn\u2019t been pushed to mutate so much. In addition, to avoid confusion in their research results, the researchers reset some of the mutations N2 did happen to undergo.\u003C\/p\u003E\u003Cp\u003EThe comparison led to swift evidence in LSJ2.\u0026nbsp; \u201cEvery single time, it pointed us to the same genetic region on the right arm of chromosome 2,\u201d McGrath said.\u0026nbsp; \u003Cem\u003EC. elegans\u003C\/em\u003E has six chromosomes.\u003C\/p\u003E\u003Cp\u003E\u201cThere were only five genes that were candidates.\u0026nbsp; One of the mutations was a smoking gun -- a 60-base-pair deletion just at the end of the NURF-1 gene.\u201d\u003C\/p\u003E\u003Cp\u003ENURF-1 has the function of remodeling chromatin, which pairs DNA with proteins to wrap them into chromosomes.\u0026nbsp; The resulting configurations strongly influence which genes are expressed. It appears the tiny mutation in the remodeling gene may have led to a massive change in the expression of other genes.\u003C\/p\u003E\u003Cp\u003EThere are missing pieces needed to understand the pathway from the mutated gene to the massive real-life changes, and the researchers are working to fill them in.\u003C\/p\u003E\u003Ch4\u003EWorm whoopy\u003C\/h4\u003E\u003Cp\u003ETo confirm the mutation as the trigger of the changes, Xu deployed a CRISPR Cas9 gene editor into N2 worms to make the deletion that LSJ2 had received via mutation, and the results left little doubt.\u003C\/p\u003E\u003Cp\u003E\u201cIt had a lot of the same effects \u2013 longer life, dauer formation,\u201d Xu said.\u0026nbsp; \u201cThe main difference was the reduction of reproduction rates. It was only about half as much in the comparison worm that got the gene editing.\u201d\u003C\/p\u003E\u003Cp\u003EBy the way, as sex goes, \u003Cem\u003EC. elegans\u003C\/em\u003E are mostly hermaphrodites that produce eggs and their own sperm to fertilize them with.\u0026nbsp; But there are also males that copulate with the hermaphrodites to add new sperm and with it genetic diversity.\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EEdward E. Large, Yuehui Zhao and Lijiang Long from Georgia Tech; Shannon Brady and Erik Andersen from Northwestern University, and Rebecca Butcher from the University of Florida coauthored the paper.\u0026nbsp; Research was sponsored by grants from the National Institutes of Health (numbers R21AG050304 and R01GM114170) and by an Ellison Medical Foundation New Scholar in Aging grant.\u003C\/em\u003E\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":[{"value":"Tiny mutation triggers huge reshuffle of reproduction and longevity"}],"field_summary":[{"value":"\u003Cp\u003ESuddenly, a roundworm overhauls an array of survival strategies, and researchers suspect multiple mutations caused them. But they\u0027re surprised when they trace the sweeping changes back to one tiny mutation on a single gene. It\u0027s a great hint at a genetic regulator of so-called life history trade-offs, a much observed natural phenomenon.\u003C\/p\u003E\u003Cp\u003EScience synopsis: Possible regulator gene for life history trade-offs found via pleiotropic NURF-1 mutation in \u003Cem\u003EC. elegans\u003C\/em\u003E; confirmed with CRISPR Cas9\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Do genetic regulators guide survival strategies in hard times? A tiny mutation in a roundworm says they may well."}],"uid":"31759","created_gmt":"2016-07-28 12:13:30","changed_gmt":"2016-10-08 03:22:12","author":"Ben Brumfield","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2016-07-28T00:00:00-04:00","iso_date":"2016-07-28T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"556381":{"id":"556381","type":"image","title":"C. elegans lab strains Patrick McGrath","body":null,"created":"1469719669","gmt_created":"2016-07-28 15:27:49","changed":"1475895355","gmt_changed":"2016-10-08 02:55:55","alt":"C. elegans lab strains Patrick 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