The study, “Deep cis-regulatory homology of the butterfly wing pattern ground plan,” published as the cover story in the Oct. 21 issue of Science, explains how DNA that sits between genes — called ‘junk’ DNA or non-coding regulatory DNA — accommodates a basic plan conserved over tens to hundreds of millions of years while at the same time allowing wing patterns to evolve extremely quickly.

The research supports the idea that an ancient color pattern ground plan is already encoded in the genome and that non-coding regulatory DNA works like switches to turn up some patterns and turn down others.

“We are interested to know how the same gene can build these very different looking butterflies,” said Anyi Mazo-Vargas, Ph.D. ’20, the study’s first author and a former graduate student in the lab of senior author, Robert Reed, professor of ecology and evolutionary biology in the College of Agriculture and Life Sciences. Mazo-Vargas is currently a postdoctoral researcher at George Washington University.

“We see that there’s a very conserved group of switches [non-coding DNA] that are working in different positions and are activated and driving the gene,” Mazo-Vargas said.

Previous work in Reed’s lab has uncovered key color pattern genes: one (WntA) that controls stripes and another (Optix) that controls color and iridescence in butterfly wings. When the researchers disabled the Optix gene, the wings appeared black, and when the WntA gene was deleted, stripe patterns disappeared.

This study focused on the effect of non-coding DNA on the WntA gene. Specifically, the researchers ran experiments on 46 of these non-coding elements in five species of nymphalid butterflies, which is the largest family of butterflies.

In order for these non-coding regulatory elements to control genes, tightly wound coils of DNA become unspooled, a sign that a regulatory element is interacting with a gene to activate it, or in some cases, turn it off.

In the study, the researchers used a technology called ATAC-seq to identify regions in the genome where this unraveling is occurring. Mazo-Vargas compared ATAC-seq profiles from the wings of five butterfly species, in order to identify genetic regions involved in wing pattern development. They were surprised to find that a large number of regulatory regions were shared across very different butterfly species.

Mazo-Vargas and colleagues then employed CRISPR-Cas gene editing technology to disable 46 regulatory elements one at a time, in order to see the effects on wing patterns when each of these non-coding DNA sequences were broken. When deleted, each non-coding element changed an aspect of the wing patterns of the butterflies.

The researchers found that across four of the species — Junonia coenia (buckeye), Vanessa cardui (painted lady), Heliconius himera and Agraulis vanillae (gulf fritillary) — each of these non-coding elements had similar functions with respect to the WntA gene, proving they were ancient and conserved, likely originating in a distant common ancestor.

They also found that D. plexippus (monarch) used different regulatory elements from the other four species to control its WntA gene, perhaps because it lost some of its genetic information over its history and had to reinvent its own regulatory system to develop its unique color patterns.

“We have progressively come to understand that most evolution occurs because of mutations in these non-coding regions,” Reed said. “What I hope is that this paper will be a case study that shows how people can use this combination of ATAC-seq and CRISPR to begin to interrogate these interesting regions in their own study systems, whether they work on birds or flies or worms.”

The study was funded by the National Science Foundation (NSF).

“This research is a breakthrough for our understanding of the genetic control of complex traits, and not only in butterflies,” said Theodore Morgan, a program director at the NSF. “Not only did the study show how the instructions for butterfly color patterns are deeply conserved across evolutionary history, but it also revealed new evidence for how regulatory DNA segments positively and negatively influence traits such as color and shape.”

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Materials provided by Cornell University. Original written by Krishna Ramanujan, courtesy of the Cornell Chronicle. Note: Content may be edited for style and length.

Circadian rhythms, sometimes called the “biological clock,” is the cellular process that rules sleep-wake cycles. The World Health Organization has proclaimed that disrupted circadian rhythms are a probable carcinogen.

The latest research, published in the high-impact journal Science Advances, describes that when the circadian clock gets off track it implicates a cancer-signature gene known as HSF1 that can trigger lung tumors. Lungs are under tight circadian control and seem to be particularly vulnerable to a disrupted biological clock.

The paper describes in mouse models the role of HSF1 signaling, a previously unknown mechanism that may explain tumor formation in response to rhythm disruption.

The findings also suggest that it may be possible to target HSF1 with drug therapy, to prevent cancer among people with frequently disturbed circadian rhythms.

Although this study was done in mice, other data link circadian disruption to human tumors, said co-author Brian Altman, Ph.D., an assistant professor of Biomedical Genetics at the University of Rochester Medical Center and a Wilmot faculty member.

“Everything points in the same direction,” he said. He noted that in this case, when the circadian clocks in mice are disrupted by inconsistent sleep, for example, the outcomes are highly relevant to people who work night shifts or rotating schedules.

Altman’s chief contribution to the study was to provide expertise on a scientific method to assess how the circadian clock behaves in tissues. The Scripps team reached out to Altman to collaborate after seeing a presentation he gave at a scientific meeting on use of the technique, which was invented in 2018 at Vanderbilt University by Jacob Hughey, Ph.D. Altman and his lab have been focused on circadian rhythms and the connection to cancer for several years.

Lead author of the study is Katja Lamia, Ph.D., associate professor of Molecular Medicine at Scripps. The Scripps news release is here. Funding was provided by the National Science Foundation and the National Institutes of Health.

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Materials provided by University of Rochester Medical Center. Original written by Leslie Orr. Note: Content may be edited for style and length.

Researchers scoured paleontological records to compare the historic distribution of Asia’s 14 largest species with their populations in present-day tropical forests.

PhD candidate Zachary Amir, from UQ’s School of Biological Sciences and the Ecological Cascades Lab, said four species — tigers, Asian elephants, wild boars and clouded leopards — showed increased populations in areas with human infrastructure.

“These results show that, under the right conditions, some large animals can live nearby humans and avoid extinction,” Mr Amir said.

“These results challenge the narrative within some conservation circles that humans and megafauna are incompatible.

“Globally there is a trend towards ‘trophic downgrading’, a term referring to the disproportionate loss of the world’s largest animals.

“Trophic downgrading is usually worst near humans because hunters target larger species.

“But in the case of tigers, elephants, wild boars and clouded leopards, their Asian populations are higher nearby humans.

“This may be the outcome of tougher anti-poaching efforts in the national parks that are closer to human settlements and are more frequently visited by tourists.”

The study also found deforestation was still impacting species, and clouded leopard numbers in particular experienced a strong decline in those areas.

But, Mr Amir said the research showed that if the large animal species were not hunted, they could live in relatively small habitats and near humans.

“Previously, there have only been a few examples of large Asian species thriving in small habitats near humans, notably in Mumbai, India where leopards in an urban park prey on stray dogs,” Mr Amir said referring to a prior UQ study.

“Thankfully, we found that a wider range of animals can coexist with humans.”

At one of their study sites in Singapore, where poaching has been eliminated and there are considerable forest restoration efforts, two large animal species are thriving again.

“Singapore has actually experienced the natural re-wilding of sambar deer and wild boars, which are now frequently observed in an urban forest, the Bukit Timah Nature Reserve,” Mr Amir said.

“If we replicate those protection efforts in larger forests and other counties, we may see positive impacts right around the world.

“But before this can happen, humans need to get our act together and limit poaching.”

While there are some positive results, UQ’s Dr Matthew Luskin said the study also noted strong declines in tapirs, Sumatran rhinoceros, sun bears, guar and other large animals.

“The key innovation of this work was to systematically investigate the population trends of many different wildlife species across the region,” Dr Luskin said.

“Then we tested if all species showed consistent trends and if similar parks retained similar species.

“Remarkably, we found no two forests currently possess the same group of wildlife compared to thousands of years ago.”

Dr Luskin said the research offered an opportunity to shape the future of nature.

“These results provide hope for wildlife in forests previously considered too far degraded or too close to cities,” he said.

“Now we’re exploring new conservation strategies for these surprising places.”

John Innes Centre researchers have shown that calcium waves are not a primary response, but rather they are a secondary response to a wave of amino acids released from the wound.

These findings challenge established thinking on long distance plant signalling molecules and the mechanisms by which information travels from the point of stress through living and non-living plant tissues.

It has been observed for many years that wounding, and other trauma, initiates calcium waves that travel both short distances from cell to cell, and longer distances from leaf to leaf.

These calcium waves are reminiscent of signalling seen in the nerves in mammals, but as plants do not have nerve cells the mechanism by which this happens has been in question.

The new findings which appear in Scientific Advances suggest that when a cell is wounded, it releases a wave of glutamate, an amino acid. As this wave travels through plant tissues, it activates calcium channels in the membranes of the cells it passes. This activation appears like a calcium wave but is a passive response, or “readout” of the moving glutamate signal.

Previous hypotheses to explain how calcium waves pass through plant cells involved active mechanisms to propagate the calcium signal. These hypotheses relied on the signal propagating along the cell membrane, or via a pressure wave in the xylem, but there was no explanation for how the response passed from one cell to the next.

Dr Christine Faulkner, Group Leader at the John Innes Centre said, “Every time active propagation models were presented, I would question how this wave travelled from cell to cell. It appeared to me that there was a hole in the theory, and this research uncovers a new mechanism that shows that the calcium wave isn’t what it seems.”

Dr Faulkner’s group specializes in the study of plasmodesmata, the channels or bridges that connect cells and the team speculated that a wound signal would travel from cell to cell through plasmodesmata. However, using quantitative imaging techniques, data modelling and genetics they found that the mobile signal is a glutamate wave that travels outside of cells, along the cell walls.

“The glutamate and calcium waves are connected — glutamate triggers the calcium response. You could imagine it with an analogy of a corridor. The glutamate rushes down the corridor and as it passes a door it kicks it open. The calcium response is the door opening. Up to now the assumption has been that what moved down the corridor was hydraulic pressure or a series of propagating chemical reactions, but our study shows that this is not the case,” said Dr Faulkner.

First author of the study Dr Analisa Bellandi said, “We’ve shown that calcium waves are synchronous with glutamate waves, and their dynamics match transmission by diffusion and flow. This research makes us rethink what we know. I am hoping that our research will inspire debate and allow people to take a fresh perspective on data which has been in the field for a long time.”

Diffusion and bulk flow of amino acids mediate calcium waves in plants appears in Science Advances.

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Materials provided by John Innes Centre. Note: Content may be edited for style and length.

Women with a first-degree family relative diagnosed with breast cancer, who are otherwise at average risk, are often advised to get screened 10 years earlier than the relative’s diagnosis age. However, there is little evidence to support the long-standing recommendation.

UC Davis Comprehensive Cancer Center researcher Diana Miglioretti joined Danielle Durham, with the Department of Radiology at University of North Carolina at Chapel Hill, and five other researchers on the study. They analyzed data from the Breast Cancer Surveillance Consortium on screening mammograms conducted from 1996-2016 to evaluate when screenings should begin for women with a family history of breast cancer.

More than 300,000 women were included in the national study. Researchers compared cumulative 5-year breast cancer incidence among women with and without a first-degree family history of breast cancer by relative’s age at diagnosis and screening age.

“The study concluded that a woman with a relative diagnosed at or before age 45 may wish to consider, in consultation with her doctor, initiating screening 5-8 years earlier than their relative’s diagnosis age, rather than a decade earlier. That puts them at a risk that is equal to that of an average-risk woman who is age 50, which is the most recommended age for starting mammograms,” said Durham.

BRCA gene mutation carriers may benefit from starting screenings earlier. Women ages 30-39 with more than one first-degree relative diagnosed with breast cancer may wish to consider genetic counseling.

Increasing the age for initiating screening could reduce the potential harms of starting breast cancer screenings too early. These include increased radiation exposure and false positive results that require women to return to the clinic for diagnostic imaging and possibly invasive procedures, but do not result in a breast cancer diagnosis. The earlier a woman starts receiving mammograms, the more screenings they will undergo over their lifetime — and that increases the chances of experiencing these harms.

“Mammography also may not perform as well in younger women because they are more likely to have dense breasts which increase the difficulty of finding cancer on the images and results in more false-positives,” Miglioretti said.

The other authors on this study include Linn A. Abraham, Kaiser Permanente Washington Health Research Institute; Megan C. Roberts, UNC Eshelman School of Pharmacy; Carly P. Khan, Patient-Centered Outcomes Research Institute; Robert A. Smith, American Cancer Society and Karla Kerlikowske, UCSF Health. Miglioretti is an affiliate investigator with UC Davis Center for Healthcare Policy and Research and Kaiser Permanente Washington Health Research.

The study was supported through funding by the Cancer Prevention Fellowship Program, Division of Cancer Prevention and the National Cancer Institute (NCI) at the National Institutes of Health. Data collection by the Breast Cancer Surveillance Consortium was funded by the NCI (grant numbers P01CA154292, U54CA163303 and PCS-1504-30370).

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Materials provided by University of California – Davis Health. Original written by Stephanie Winn. Note: Content may be edited for style and length.