Viruses: Manufacturing Tycoons?

Pseudomonas chlororaphis

A computer image shows a bacterial cell invaded by a virus. The virus uses the cell to copy itself many times. It has built a protein compartment (red, rough circle surrounding the center) to house its DNA. Viral heads (blue, smaller pentagonal shapes spread through out) and tails (pink, rod shaped near the edges) are essential parts of a finished viral particle. The small, light blue particles are the bacterium’s own protein-making ribosomes. Credit: Vorrapon Chaikeeratisak, Kanika Khanna, Axel Brilot and Katrina Nguyen.

As inventors and factory owners learned during the Industrial Revolution, the best way to manufacture a lot of products is with an assembly line that follows a set of precisely organized steps employing many copies of identical and interchangeable parts. Some viruses are among life’s original mass producers: They use sophisticated organization principles to turn bacterial cells into virus particle factories.

Scientists at the University of California, San Diego, and the University of California, San Francisco, used cutting-edge techniques to watch a bacteria-infecting virus (bacteriophage) set up its particle-making factory inside a host cell.

The image above shows this happening inside a Pseudomonas chlororaphis, a soil-borne bacterium that protects plants against fungal pathogens. The virus builds a compartment (red, rough circle surrounding the center) that helps organize an assembly line for making copies of itself. The compartment looks like a cell nucleus, which bacteria do not have, and it functions like a nucleus by keeping activities that directly involve DNA separate from other cellular functions. Continue reading

Six Things to Know About DNA and DNA Repair

Deoxyribonucleic acid, better known as DNA, was first identified on a discarded surgical bandage almost 150 years ago. Increasingly sophisticated tools and techniques have allowed scientists to learn more about this chemical compound that includes all the instructions necessary for building a living organism. From among the dozens of fascinating things known about DNA, here are six items touching on the make up of DNA’s double helix, the vast amounts of DNA packed into every human’s cells, common DNA errors and a few ways DNA can repair itself.

1. DNA is in every living thing.

Nucleotide
DNA consists of two long, twisted chains made of nucleotides. Each nucleotide contains one base, one phosphate molecule and the sugar molecule deoxyribose. The bases in DNA nucleotides are adenine, cytosine, guanine and thymine. Credit: NIGMS.

The chemical instructions for building a person—and every other creature on Earth—are contained in DNA. DNA is shaped like a corkscrew-twisted ladder, called a double helix. The two ladder rails are referred to as backbones, made of alternating groups of sugar and phosphate. The ladder’s rungs are made from four different building blocks called bases, arranged in pairs: adenine (A) paired with thymine (T), and cytosine (C) paired with guanine (G). Humans have about 3 billion base pairs in each cell. The order of the base pairs determines the exact instructions encoded in that part of the DNA molecule. Also, the sequence of DNA base pairs in one person is about 99.9 percent identical to that of everyone else.

2. Humans have a lot of DNA.

Humans begin as a single fertilized cell containing (with some rare exceptions) the full complement of DNA—the genome—arranged into 46 discrete chromosomes (23 pairs, with mom and dad each contributing half of each pair) in the cell’s nucleus. There are about 5 feet of DNA coiled up tightly in that first cell. All the information in the DNA is replicated each time the cell divides. The amount of DNA packed into all of an adult’s cells is on the order of 100 trillion feet (about 19 billion miles)—so that if the DNA chain was stretched out, it would be long enough to reach back and forth between the Earth and the Sun more than 200 times. Continue reading

Birthdays, Nobel Prizes and Basic Research

James D. Watson
James D. Watson. Credit: Wikimedia Commons, Cold Spring Harbor Laboratory.

April 6 is the birthday of two Nobel Prize winners in physiology or medicine—James Watson and Edmond H. Fischer. They have also both been NIGMS-supported researchers.

Double helix model
In 1953, Watson and Crick created their historic model of the shape of DNA: the double helix. Credit: Cold Spring Harbor Laboratory archives.

James D. Watson, born on this day in 1928, was honored with the Nobel Prize in 1962. He shared it with Francis H. Compton Crick and Maurice Wilkins “for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material.” This laid the groundwork for future discoveries. In the early 1950s, Wilkins and another scientist, Rosalind Franklin, worked to determine DNA’s structure. In 1953, Watson and Crick discovered its shape as a double helix. This twisted ladder structure enabled other researchers to unlock the secret of how genetic information is stored, transferred and copied. Franklin is widely recognized as having played a significant role in revealing the physical structure of DNA; due to her death at age 37 in 1958, Franklin did not earn a share of the prize. Read more about DNA. Continue reading

Field Focus: High-Quality Genome Sequences Inform the Study of Human Evolution

Leafing through my favorite biology textbook from a handful of years ago, I was struck by the relative brevity of the chapter on human evolution. While other fields of biological research have enjoyed a steady gallop of productivity over the last few decades due in part to advances in computing power, imaging technology and experimental methods, the study of human evolution can be seen as having lagged behind until recently due to an almost complete dependence on fossil evidence.

Fortunately, contemporary biology textbook chapters on human evolution are being primed for a serious upgrade thanks to the recent availability of high-quality genome sequences from diverse modern human populations as well as from ancient humans and other non-human hominids, including the Neanderthals and Denisovans (but, for purposes of this story, not the Great Apes).

Modern human skull (left) and Neanderthal skull (right), shown to scale. There are not enough Denisovan bone fragments to reconstruct its skull. Credit: Wikimedia Commons, hairymuseummatt.

What are the new resources for studying human evolution?

The cost of DNA sequencing has dropped precipitously in the last decade. As a result, more complete human genome sequences become available for analysis with each passing year.

For example, the 1000 Genomes Project Exit icon includes more than 1,000 full human genome sequences of individuals from European, Asian, American and Sub-Saharan African populations. Earlier this year, the Simons Genome Diversity Project Exit icon further increased the number of available human genomes by adding 300 individuals representing 142 populations around the globe. Continue reading

Our Complicated Relationship With Viruses

Illustration of Influenza Virus H1N1. Swine Flu.
Nearly 10 percent of the human genome is derived from the genes of viruses. Credit: Stock image.

When viruses infect us, they can embed small chunks of their genetic material in our DNA. Although infrequent, the incorporation of this material into the human genome has been occurring for millions of years. As a result of this ongoing process, viral genetic material comprises nearly 10 percent of the modern human genome. Over time, the vast majority of viral invaders populating our genome have mutated to the point that they no longer lead to active infections. But they are not entirely dormant.

Sometimes, these stowaway sequences of viral genes, called “endogenous retroviruses” (ERVs), can contribute to the onset of diseases such as cancer. They can also make their hosts susceptible to infections from other viruses. However, scientists have identified numerous cases of viral hitchhikers bestowing crucial benefits to their human hosts—from protection against disease to shaping important aspects of human evolution, such as the ability to digest starch.

Protecting Against Disease

Geneticists Cedric Feschotte Exit icon, Edward Chuong Exit icon and Nels Elde Exit icon at the University of Utah have discovered that ERVs lodged in the human genome can jump start the immune system.

For a virus to successfully make copies of itself inside a host cell, it needs molecular tools similar to the ones its host normally uses to translate genes into proteins. As a result, viruses have tools meticulously shaped by evolution to commandeer the protein-producing machinery of human cells. Continue reading

Cool Image: DNA Origami

Computer-generated sketch of a DNA origami folded into a flower-and-bird structure.

A computer-generated sketch of a DNA origami folded into a flower-and-bird structure. Credit: Hao Yan, Arizona State University.

This image of flowers visited by a bird is made of DNA, the molecule that provides the genetic instructions for making living organisms. It shows the latest capability of a technique called DNA origami to precisely twist and fold DNA into complex arrangements, which might find future use in biomedical applications. Continue reading

Unusual DNA Form May Help Virus Withstand Extreme Conditions

A, B and Z DNA.
DNA comes in three forms: A, B and Z. Credit: A-DNA, B-DNA and Z-DNA by Zephyris (Richard Wheeler) under CC BY-SA 3.0.

DNA researcher Rosalind Franklin Exit icon first described an unusual form of DNA called the A-form in the early 1950s (Franklin, who died in 1958, would have turned 95 next month). New research on a heat- and acid-loving virus has revealed surprising information about this DNA form, which is one of three known forms of DNA: A, B and Z.

“Many people have felt that this A-form of DNA is only found in the laboratory under very non-biological conditions, when DNA is dehydrated or dry,” says Edward Egelman Exit icon in a University of Virginia news release Exit icon about the recent study. But considered with earlier studies on bacteria by other researchers, the new findings suggest that the A-form “appears to be a general mechanism in biology for protecting DNA.” Continue reading

Delivering Gene-Editing Proteins to Living Cells

Illustration of a DNA strand being cut by a pair of scissors.
Researchers are testing new ways to get gene editing proteins into living cells to potentially modify human genes associated with disease. Credit: Stock image.

Over the last two decades, exciting tools have emerged that allow researchers to cut and paste specific sequences of DNA within living cells, a process called gene editing. These tools, including one adapted from a bacterial defense system called CRISPR, have energized the research community with the possibility of using them to modify human genes associated with disease.

A major barrier to testing medical applications of gene editing has been getting the proteins that do the cutting into the cells of living animals. The main methods used in the laboratory take a roundabout route: Researchers push the DNA templates for making the proteins into cells, and then the cells’ own protein factories produce the editing proteins.

Researchers led by David Liu Exit icon from Harvard University are trying to cut out the middleman, so to speak, by ferrying the editing proteins, not the DNA instructions, directly into cells. In a proof-of-concept study, their system successfully delivered three different types of editing proteins into cells in the inner ears of live mice. Continue reading

Neanderthal DNA—Still Among Us

Map of Europe and Asia showing the presumed range of where Neanderthals lived.
For tens of thousands of years, Neanderthals lived in Europe and Asia (presumed range shown in blue) and interbred with humans, passing on some DNA to present-day people. Credit: Ryulong, Wikimedia Commons.
View larger image

Many of us have some Neanderthal genes. Before Neanderthals went extinct about 30,000 years ago, they interbred with humans living in Europe and Asia. Today’s descendants of those pairings inherited about 2 percent of their genomes from the big-brained hominids.

A research group led by David Reich at Harvard Medical School recently completed an analysis to determine the extent and identity of Neanderthal DNA in modern-day human populations. The group found that many traits in present-day people—including skin characteristics and susceptibility to various diseases—can be traced to Neanderthal DNA.

It also appears that, genetically speaking, Neanderthals and humans weren’t completely compatible. Based on the uneven distribution of Neanderthal DNA in today’s genomes, the scientists concluded that many of the male offspring of Neanderthal-human unions were infertile. In the animal world, this phenomenon is known as hybrid infertility, where the offspring of a male from one subspecies and a female from another have low or no fertility.

Studying human genes passed down through Neanderthals—as well as regions of the human genome notably devoid of Neanderthal DNA—provides an increasingly complete picture of the genetic landscape that contributed to health, disease and diversity among humans today.

Learn more:
Harvard Medical School News Release Exit icon
Evolution and Health Article from Inside Life Science
Reich Lab Exit icon