On this Darwin Day, Evolutionary Geneticist Dr. Dan Janes Discusses the Scientific Contributions of Charles Darwin

This Sunday, February 12, is Darwin Day—an occasion to recognize the scientific contributions of 19th-century naturalist Charles Darwin. In this video (originally posted on Darwin Day 2016), our own evolutionary geneticist, Dan Janes, answers questions about Darwin and the role of evolution in health and biomedicine.

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Four Ways Inheritance Is More Complex Than Mendel Knew

Original edition of Gregor Mendel’s 1866 publication, Experiments in Plant Hybridization
An original edition of Gregor Mendel’s 1866 publication, “Experiments in Plant Hybridization,” housed in NIH’s National Library of Medicine. Credit: Alisa Machalek.

This year marks the 150th anniversary of Gregor Mendel’s publication that—after sitting ignored for a few decades—helped launch the field of modern genetics. Mendel didn’t know about DNA. But after painstakingly cross-fertilizing tens of thousands of pea plants over the course of 8 years, this Austrian monk came very close to describing genes.

By picking a species with a handful of visible characteristics that occur in two easily identifiable forms, Mendel was able to pinpoint what he called “factors.” These factors determine traits like a pea’s shape or color, for instance, and are passed down from parents to offspring. He also observed that factors can be dominant or recessive.

Today, we know that inheritance is far more complex than what Mendel saw in his pea plants. Here are some of the things scientists have learned about how traits are passed from one generation to the next. Continue reading

Evolution and Health: A Conversation with Evolutionary Geneticist Dr. Dan Janes on the Occasion of Charles Darwin’s Birthday

Today, February 12, is Darwin Day—an occasion to recognize the scientific contributions of 19th-century naturalist Charles Darwin. In this video, our own evolutionary geneticist, Dan Janes, answers questions about Darwin and the role of evolution in health and biomedicine.

For more details about evolution and you, check out our articles Evolution and Health and Everyday Evolution.

Field Focus: Progress in RNA Interference Research

Scientists first noticed what would later prove to be RNA interference when puzzling over an unexpected loss of color in petunia petals. Subsequent studies in roundworms revealed that double-stranded RNA can inactivate specific genes. Credit: Alisa Z. Machalek.

In less than two decades, RNA interference (RNAi)—a natural process cells use to inactivate, or silence, specific genes—has progressed from a fundamental finding to a powerful research tool and a potential therapeutic approach. To check in on this fast-moving field, I spoke to geneticists Craig Mello Exit icon of the University of Massachusetts Medical School and Michael Bender of NIGMS. Mello shared the 2006 Nobel Prize in physiology or medicine with Andrew Fire Exit icon of Stanford University School of Medicine for the discovery of RNAi. Bender manages NIGMS grants in areas that include RNAi research.

How have researchers built on the initial discovery of RNAi?

A scientific floodgate opened after the 1998 discovery that it was possible to switch off specific genes by feeding microscopic worms called C. elegans double-stranded RNA that had the same sequence of genetic building blocks as a target gene. (Double-stranded RNA is a type of RNA molecule often found in, or produced by, viruses.) Scientists investigating gene function quickly began to test RNAi as a gene-silencing technique in other organisms and found that they could use it to manipulate gene activity in many different model systems. Additional studies led the way toward getting the technique to work in cells from mammals, which scientists first demonstrated in 2001. Soon, researchers were exploring the potential of RNAi to treat human disease. Continue reading

How Instructions for Gene Activity Are Passed Across Generations

C. elegans embryos
Images of C. elegans embryos show transmission of an epigenetic mark (green) during cell division from a one-cell embryo (left) to a two-cell embryo (right). Credit: Laura J. Gaydos.

Chemical tags that cells attach to DNA or to DNA-packaging proteins across the genome—called epigenetic marks—can alter gene activity, or expression, without changing the underlying DNA code. As a result, these epigenetic changes can influence health and disease. But it’s a matter of debate as to whether and how certain epigenetic changes on DNA-packaging proteins can be passed from parents to their offspring.

In studies with a model organism, the worm C. elegans, researchers led by Susan Strome Exit icon of the University of California, Santa Cruz, have offered new details that help resolve the debate.

Strome’s team created worms with a genetic change that knocks out the enzyme responsible for making a particular methylation mark, a type of epigenetic mark that can turn off gene expression at certain points of an embryo’s development. Then the scientists bred the knockout worms with normal ones. Looking at the chromosomes from the resulting eggs, sperm and dividing cells of embryos after fertilization, the researchers found that the methylation marks are passed from both parents to offspring. The enzyme, however, is passed to the offspring just by the egg cell. For embryos with the enzyme, the epigenetic marks are passed faithfully through many cell divisions. For those without it, the epigenetic mark can be passed through a few cell divisions.

Because all animals use the same enzyme to create this particular methylation mark, the results have implications for parent-to-child epigenetic inheritance as well as cell-to-cell inheritance in other organisms.

This work was funded in part by NIH under grants R01GM034059, T32GM008646 and P40OD010440.

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Dynamic DNA Section from The New Genetics Booklet

New Research Sheds Light on Drug-Induced Salivary Issues

Open human mouth
Scientists have discovered a possible mechanism behind the bad taste and dry mouth caused by some drugs. Credit: Stock image.

The effects some medicines have on our salivary glands can at times extend beyond the fleeting flavor we experience upon ingesting them. Sometimes drugs cause a prolonged bad taste or dryness in the mouth, both of which can discourage people from taking medicines they need. Now, a research team led by Joanne Wang of the University of Washington has discovered a possible mechanism behind this phenomenon. Working primarily with mice and using a commonly prescribed antidiabetic drug known to impair taste, the scientists identified a protein in salivary gland cells that takes up the drug from the bloodstream and secretes it in saliva. Wang and her colleagues were also able to pinpoint a specific gene that, when removed, hindered this process. They hope their new insights will aid efforts to develop medicines that do not cause salivary issues.

This work also was funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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Raking the Family Tree for Disease-Causing Variations

Silhouettes of people with nucleic acid sequences and a stethoscope.
A new software tool analyzes disease-causing genetic variations within a family. Credit: NIH’s National Human Genome Research Institute.

Changes in your DNA sequence occur randomly and rarely. But when they do happen, they can increase your risk of developing common, complex diseases, such as cancer. One way to identify disease-causing variations is to study the genomes of family members, since the changes typically are passed down to subsequent generations.

To rake through a family tree for genetic variations with the highest probabilities of causing a disease, researchers combined several commonly-used statistical methods into a new software tool called pVAAST. The scientific team, which included Mark Yandell and Lynn Jorde of the University of Utah and Chad Huff of the University of Texas MD Anderson Cancer Center, used the tool to identify the genetic causes of a chronic intestinal inflammation disease and of developmental defects affecting the heart, face and limbs.

The results confirmed previously identified genetic variations for the developmental diseases and pinpointed a previously unknown variation for the intestinal inflammation. Together, the findings confirm the ability of the tool to detect disease-causing genetic changes within a family. Another research team has already used the software tool to discover rare genetic changes associated with family cases of breast cancer. These studies are likely just the beginning for studying genetic patterns of diseases than run in a family.

This work also was funded by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases; National Cancer Institute; National Human Genome Research Institute; National Heart, Lung, and Blood Institute; and National Institute of Mental Health.

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Cool Image: Researching Regeneration in a Model Organism

The isolated feeding tube of a flatworm.

The feeding tube, or pharynx, of a planarian worm with cilia shown in red and muscle fibers shown in green. Credit: Carrie Adler/Stowers Institute for Medical Research.

This rainbow-hued image shows the isolated feeding tube, or pharynx, of a tiny freshwater flatworm called a planarian, with the hairlike cilia in red and muscle fibers in green. Scientists use these wondrous worms, which have an almost infinite capacity to regrow all organs, as a simple model system for studying regeneration. A research team led by Alejandro Sánchez Alvarado of the Stowers Institute for Medical Research exploited a method known as selective chemical amputation to remove the pharynx easily and reliably. This allowed the team to conduct a large-scale genetic analysis of how stem cells in a planaria fragment realize what’s missing and then restore it. The researchers initially identified about 350 genes that were activated as a result of amputation. They then suppressed those genes one by one and observed the worms until they pinpointed one gene in particular—a master regulator called FoxA—whose absence completely blocked pharynx regeneration. Scientists believe that researching regeneration in flatworms first is a good way to gain knowledge that could one day be applied to promoting regeneration in mammals.

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One Mutation Leads to Another—At Least in Yeast

DNA mutation. Credit: Stock image.
Newly discovered genetic effect in yeast could shed light on carcinogenesis. Credit: Stock image.

Cancer cells typically include many gene mutations, extra or missing genes, or even the wrong number of chromosomes. Scientists know that certain genetic changes lead to ones elsewhere. But they’ve had a chicken-and-egg problem trying to figure out which changes trigger which others—or whether mutations accumulate randomly in tumors.

New research led by J. Marie Hardwick Exit icon of Johns Hopkins University sheds light on the issue. She found that incapacitating a single gene in yeast cells—regardless of which gene it was—spurred mutations in one or two other genes. The process was anything but random: If, say, gene X was knocked out, yeast cells almost always developed a secondary mutation in gene Y. It’s as if knocking out one gene disrupts the genomic balance enough that the cell must alter a different gene to compensate.

Significantly, the secondary mutations—but not the original ones—caused altered yeast cell characteristics, including traits linked to cancer. Also, many of the secondary mutations occurred in genes associated with cancer in humans, further suggesting that these secondary changes might play a role in carcinogenesis.

This new information will help researchers better understand the chain of genetic events that lead to cancer. It might also prompt scientists to reevaluate years of research that attributed changes in cell behavior or appearance to a given gene knockout.

This work also was funded by NIH’s National Institute of Neurological Disorders and Stroke.

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Genetic Discovery Could Enable More Precise Prescriptions

Prescription pad with DNA illustration on it. Credit: Jane Ades, NIH’s National Human Genome Research Institute.
New insight into the genes that affect drug responses may help doctors prescribe the medications and doses best suited for each individual. Credit: Jane Ades, NIH’s National Human Genome Research Institute.

Scientists know that variations in certain genes can affect the way a person responds to medications. New research by Wolfgang Sadee Exit icon at Ohio State University shows that drug responses also depend on previously overlooked parts of DNA—sections that regulate genes, but are not considered genes themselves. This study focused on an important enzyme abbreviated CYP2D6 that processes about one-fourth of all prescription drugs. Differences in the enzyme’s performance, which range from zilch to ultra-rapid, can dramatically alter the effectiveness and safety of certain medications. Researchers discovered two new genetic variants that impact CYP2D6 performance. One of these, located in a non-gene, regulatory region of DNA, doubles or even quadruples enzyme activity. Coupling these findings with genetic tests could help doctors better identify each patient’s CYP2D6 activity level, enabling more precise prescriptions. The findings also open up a whole new area of investigation into genetic factors that impact drug response.

This work also was funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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Using Genes to Guide Prescriptions Article from Inside Life Science Series