Posts about genes

The Amazing Reality of Genes and The History of Scientific Inquiry

cover of The Gene

The Gene by Siddhartha Mukherjee is a wonderful book. He does a great job of explaining the history of scientists learning about genes as well as providing understandable explanations for the current scientific understanding of genes and how they impact our lives.

As I have mentioned before, I find biology fascinating even though I found biology classes utterly boring and painful. I wish everyone could learn about biology with the insight people like Siddhartha Mukherjee provide. I realize not everyone is going to find the history and understanding of genes to be fascinating but for those who might this book is a great read. And don’t rule the idea out just because you found biology classes painful.

Life may be chemistry, but it’s a special circumstance of chemistry. Organisms exist not because of reactions that are possible, but because of reactions that are barely possible. Too much reactivity and we would spontaneously combust. Too little, and we would turn cold and die. Proteins enable these barely possible reactions, allowing us to live on the edges of chemical entropy – skating perilously, but never falling in.
– page 134

Whether it is the physics of our solar system or our biology there is a precarious band that allowed beings such as ourselves to evolve.

most genes, as Richard Dawkins describes them, are not “blueprints” but “recipes.” They do not specify parts, but processes; they are formulas, not forms. If you change a blueprint, the final product is change in a perfectly predictable manner: eliminate a widget specified in the plan, and you get a machine with a missing widget. But alteration of a recipe or formula doesn’t not change the product in a predictable manner: if you quadruple the amount of butter in a cake, the eventual effect is more complicated than just a quadruply buttered cake (try it; the whole thing collapses in an oily mess).
– page 454

The is a powerful idea. And when combined with turning genes on and off it is understandable how complex determining genetic impacts on biology and disease are. A few diseases or results (e.g. blue eyes) are nearly as simple as 1 or a few genes being altered in a specific way but most are not nearly so easy. And it isn’t like even that is so easy but with the amazing efforts scientists have made and the advanced tools those scientists created it can now seem simple to identify some such diseases.

The genetic code is universal. A gene from a blue whale can be inserted into a microscopic bacterium and it will be deciphered accurately and with near perfect fidelity. A corollary: there is nothing particularly special about human genes.
– page 480

This is something I have known and understood but it is still amazing. Genes and proteins and how they act to create the incredible diversity of life is something that is awe inspiring.

This book is a wonderful adventure for those interested in life and scientific inquiry.

Related: Epigenetics, Scientific Inquiry and UncertaintyHuman Gene Origins: 37% Bacterial, 35% Animal, 28% EukaryoticUnexpected Risks Found In Editing Genes To Prevent Inherited DisordersEpigenetic Effects on DNA from Living Conditions in Childhood Persist Well Into Middle AgeWhy Don’t All Ant Species Replace Queens in the Colony, Since Some Do

Unexpected Risks Found In Editing Genes To Prevent Inherited Disorders

Mitochondrial replacement seeks to remove genes known to cause genetic defects from embryos in order to allow for a baby to avoid inheriting the defect.

Mitochondrial Replacement Techniques: Ethical, Social, and Policy Considerations from the USA National Academy of Sciences

Accordingly, the committee recommends that any initial MRT clinical investigations focus on minimizing the future child’s exposure to risk while ascertaining the safety and efficacy of the techniques. The recommended restrictions and conditions for initial clinical investigations include

  • limiting clinical investigations to women who are otherwise at risk of transmitting a serious mtDNA disease, where the mutation’s pathogenicity is undisputed, and the clinical presentation of the disease is predicted to be severe, as characterized by early mortality or substantial impairment of basic function; and
  • transferring only male embryos for gestation to avoid introducing heritable genetic modification during initial clinical investigations.

Following successful initial investigations of MRT in males, the committee recommends that FDA could consider extending MRT research to include the transfer of female embryos if clear evidence of safety and efficacy from male cohorts, using identical MRT procedures, were available, regardless of how long it took to collect this evidence; preclinical research in animals had shown evidence of intergenerational safety and efficacy; and FDA’s decisions were consistent with the outcomes of public and scientific deliberations to establish a shared framework concerning the acceptability of and moral limits on heritable genetic modification.

The research in this area is interesting and our ability to help achieve healthy lives continues to grow. The path to a bright future though is not without risk. It requires careful action to pursue breakthrough improvements while minimizing the risks we take to achieve better lives for us all.

Unexpected Risks Found In Editing Genes To Prevent Inherited Disorders

Earlier this month, a study published in Nature by Shoukhrat Mitalipov, head of the Center for Embryonic Cell and Gene Therapy at the Oregon Health and Science University in Portland, suggested that in roughly 15 percent of cases, the mitochondrial replacement could fail and allow fatal defects to return, or even increase a child’s vulnerability to new ailments.

The findings confirmed the suspicions of many researchers, and the conclusions drawn by Mitalipov and his team were unequivocal: The potential for conflicts between transplanted and original mitochondrial genomes is real, and more sophisticated matching of donor and recipient eggs — pairing mothers whose mitochondria share genetic similarities, for example — is needed to avoid potential tragedies.

“This study shows the potential as well as the risks of gene therapy in the germline,” Mitalipov says. This is especially true of mitochondria, because its genomes are so different than the genomes in the nucleus of cells. Slight variations between mitochondrial genomes, he adds, “turn out to matter a great deal.”

Related: Gene Duplication and EvolutionThe Challenge of Protecting Us from Evolving Bacterial ThreatsOne Species’ Genome Discovered Inside Another’s (2007)Looking Inside Living Cells

Parasite Evolved from Cnidarians (Jellyfish etc.)

This is another instance of science research providing us interesting details about the very odd ways life has evolved on earth.

Genome sequencing confirms that myxozoans, a diverse group of microscopic parasites that infect invertebrate and vertebrate hosts, are actually highly reduced cnidarians — the phylum that includes jellyfish, corals and sea anemones.

“This is a remarkable case of extreme degeneration of an animal body plan,” said Paulyn Cartwright, associate professor of ecology and evolutionary biology at the University of Kansas (KU) and principal investigator on the research project. “First, we confirmed they’re cnidarians. Now we need to investigate how they got to be that way.”

images of myxozoans parasite spores and a jellyfish

Not only has the parasitic micro jellyfish evolved a stripped-down body plan of just a few cells, but via data generated at the KU Medical Center’s Genome Sequencing Facility researchers also found the myxozoan genome was drastically simplified.

“These were 20 to 40 times smaller than average jellyfish genomes,” Cartwright said. “It’s one of the smallest animal genomes ever reported. It only has about 20 million base pairs, whereas the average Cnidarian has over 300 million. These are tiny little genomes by comparison.”

Despite its radical phasedown of the modern jellyfish’s body structure and genome over millions of years, Myxozoa has retained the essential characteristic of the jellyfish — its stinger, or “nematocyst” — along with the genes needed to make it.

“Because they’re so weird, it’s difficult to imagine they were jellyfish,” she said. “They don’t have a mouth or a gut. They have just a few cells. But then they have this complex structure that looks just like stinging cell of cnidarian. Jellyfish tentacles are loaded with them — little firing weapons.”

The findings are the stuff of scientific fascination but also could have a commercial effect. Myxozoa commonly plague commercial fish stock such as trout and salmon.

“They’re a very diverse group of parasites, and some have been well-studied because they infect fish and can wreak havoc in aquaculture of economic importance,” Cartwright said.

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Epigenetics, Scientific Inquiry and Uncertainty

Science is full of fascinating ideas. Epigenetics is one area I find particularly interesting. This previous post has a few links to learning more: DNA Passed to Descendants Changed by Your Life.

Angela Saini is one 109 people I follow on Twitter. I don’t see the point in “following” people on Twitter that you have no interest in, I only follow the small number of people that post Tweets I want to read.

In, Epigenetics: genes, environment and the generation game, Angela Saini looks at the confused state of current scientific understand now. It is very difficult to tell if, and if so, to what extent, epigenetic inheritance happens in people.

Professor Azim Surani, a leading developmental biologist and geneticist at the University of Cambridge, adds that while there is good evidence that epigenetic inheritance happens in plants and worms, mammals have very different biology. Surani’s lab carried out thorough studies on how epigenetic information was erased in developing mouse embryos and found that “surprisingly little gets through” the reprogramming process.

Professor Timothy Bestor, a geneticist at Columbia University in New York, is far more damning, claiming that the entire field has been grossly overhyped. “It’s an extremely fashionable topic right now. It’s very easy to get studies on transgenerational epigenetic inheritance published,” he says, adding that all this excitement has lowered critical standards.

Related: Epigenetic Effects on DNA from Living Conditions in Childhood Persist Well Into Middle AgeMedical Study Findings too Often Fail to Provide Us Useful KnowledgeScientific Inquiry Process Finds That Komodo Dragons Don’t have a Toxic Bite After All

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Refusal to Follow Scientific Guidance Results in Worms Evolving to Eat Corn Designed to Kill The Worms

An understanding of natural selection and evolution is fundamental to understanding science, biology, human health and life. Scientists create wonderful products to improve our lives: vaccines, antibiotics, etc.; if we don’t use them or misuse them it is a great loss to society.

There is also great value in genetic enhanced seeds and thus plants (through natural human aided processes such as breeding and providing good genetic material over a wide area – distances that would not be covered naturally, at least not in a time that helps us much). Genetic Modified Organisms (GMO) food, in which we tinker with the genes directly also holds great promise but has risks, especially if we forget basic scientific principles such as biodiversity.

Voracious Worm Evolves to Eat Biotech Corn Engineered to Kill It

First planted in 1996, Bt corn quickly became hugely popular among U.S. farmers. Within a few years, populations of rootworms and corn borers, another common corn pest, had plummeted across the midwest. Yields rose and farmers reduced their use of conventional insecticides that cause more ecological damage than the Bt toxin.

By the turn of the millennium, however, scientists who study the evolution of insecticide resistance were warning of imminent problems. Any rootworm that could survive Bt exposures would have a wide-open field in which to reproduce; unless the crop was carefully managed, resistance would quickly emerge.

Key to effective management, said the scientists, were refuges set aside and planted with non-Bt corn. Within these fields, rootworms would remain susceptible to the Bt toxin. By mating with any Bt-resistant worms that chanced to evolve in neighboring fields, they’d prevent resistance from building up in the gene pool.

But the scientists’ own recommendations — an advisory panel convened in 2002 by the EPA suggested that a full 50 percent of each corn farmer’s fields be devoted to these non-Bt refuges — were resisted by seed companies and eventually the EPA itself, which set voluntary refuge guidelines at between 5 and 20 percent. Many farmers didn’t even follow those recommendations.

Using extremely powerful tools like GMO requires society to have much better scientific literacy among those making decisions than any societies have shown thus far. The failure of our governments to enforce sensible scientific constraints on such use of genetic engineering creates huge risks to society. It is due to this consistent failure of our government to act within sensible scientific constraints that causes me to support efforts (along with other reasons – economic understanding – the extremely poor state of patent system, risk reduction…) to resist the widespread adoption of GMO, patenting of life (including seeds and seeds produced by seeds).

Wonderful things are possible. If we grow up and show a long term track record of being guided by scientific principles when the risks of not doing so are huge then I will be more supportive of using tactics such as GMO more easily. But I don’t see us getting their anytime soon. If anything we are much less scietifically minded and guided than we were 50 years ago: even while we bask in the glorious wonders science has brought us on a daily basis.

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Cell Aging and Limits Due to Telomeres

When cells divide the process fails to copy DNA all the way to the end. Telomeres are are the end of DNA strands, as essentially a buffer of material that won’t cause information to be lost when part of the telomere isn’t copied. As DNA is copied, as new cells are created, the length of telomeres at the end is reduced. Once the telomeres are gone the cell will no longer divide.

The 2009 Nobel Prize in Physiology or Medicine went to 3 scientists for discovering how the chromosomes can be copied in a complete way during cell divisions and how they are protected against degradation. The Nobel Laureates have shown that the solution is to be found in the ends of the chromosomes – the telomeres – and in an enzyme that forms them – telomerase.

There is some debate over the benefit of the mechanism of cells not dividing do to lack of telomere. This can prevent cancerous cells from replicating (once they replicate to the extent that the necessary telomere buffer is gone). It is also seen that as telomeres get shorter the cells become more likely to become cancerous.

Cancer also can stimulate the production of telomerase which can stop telomeres from getting shorter as cells divide and thus allow the cancer cells to keep dividing (thus producing more cancer cell and increasing the amount of cancerous cells). Using telomerase to allow health cells to avoid the limits of division is being researched.

Are Telomeres the Key to Aging and Cancer? (University of Utah)

An enzyme named telomerase adds bases to the ends of telomeres. In young cells, telomerase keeps telomeres from wearing down too much. But as cells divide repeatedly, there is not enough telomerase, so the telomeres grow shorter and the cells age.

Cells normally can divide only about 50 to 70 times, with telomeres getting progressively shorter until the cells become senescent, die or sustain genetic damage that can cause cancer.

shorter telomeres are associated with shorter lives. Among people older than 60, those with shorter telomeres were three times more likely to die from heart disease and eight times more likely to die from infectious disease.

While telomere shortening has been linked to the aging process, it is not yet known whether shorter telomeres are just a sign of aging – like gray hair – or actually contribute to aging.

Related: The Naked Mole Rat is the Only Known Cancerless AnimalWebcast of a T-cell Killing a Cancerous CellRNA interference webcast

People are Superorganisms With Microbiomes of Thousands of Species

In a recent article in National Geographic Carl Zimmer has again done a good job of explaining the complex interaction between our bodies and the bacteria and microbes that make us sick, and keep us healthy.

The damage done by our indiscriminate use of antibiotics is not just the long term resistance that we create in bacteria (making the future more dangerous for people) that I have written about numerous times but it also endangers the person taking the anti-biotics in the short term. Sometimes the other damage is a tradeoff that should be accepted. But far too often we ignore the damage taking antibiotics too often does.

When You Swallow A Grenade

While antibiotics can discriminate between us and them, however, they can’t discriminate between them and them–between the bacteria that are making us sick and then ones we carry when we’re healthy. When we take a pill of vancomycin, it’s like swallowing a grenade. It may kill our enemy, but it kills a lot of bystanders, too.

If you think of the human genome as all the genes it takes to run a human body, the 20,000 protein-coding genes found in our own DNA are not enough. We are a superorganism that deploys as many as 20 million genes.

Before he started taking antibiotics, the scientists identified 41 species in a stool sample. By day 11, they only found 13. Six weeks after the antibiotics, the man was back up to 38 species. But the species he carried six weeks after the antibiotics did not represent that same kind of diversity he had before he took them. A number of major groups of bacteria were still missing.

They found that children who took antibiotics were at greater risk of developing inflammatory bowel disease later in life. The more antibiotics they took, the greater the risk. Similar studies have found a potential link to asthma as well.

The human body contains trillions of microorganisms — outnumbering human cells by 10 to 1. Because of their small size, however, microorganisms make up only about 1% to 3% of the body’s mass, but play a vital role in human health.

Where doctors had previously isolated only a few hundred bacterial species from the body, Human Microbiome Project (HMP) researchers now calculate that more than 10,000 microbial species occupy the human ecosystem. Moreover, researchers calculate that they have identified between 81% and 99% of all microorganismal genera in healthy adults.

“Humans don’t have all the enzymes we need to digest our own diet,” said Lita Proctor, Ph.D., NHGRI’s HMP program manager. “Microbes in the gut break down many of the proteins, lipids and carbohydrates in our diet into nutrients that we can then absorb. Moreover, the microbes produce beneficial compounds, like vitamins and anti-inflammatories that our genome cannot produce.” Anti-inflammatories are compounds that regulate some of the immune system’s response to disease, such as swelling.

“Enabling disease-specific studies is the whole point of the Human Microbiome Project,” said Barbara Methé, Ph.D., of the J. Craig Venter Institute, Rockville, MD, and lead co-author of the Nature paper on the framework for current and future human microbiome research. “Now that we understand what the normal human microbiome looks like, we should be able to understand how changes in the microbiome are associated with, or even cause, illnesses.”

Read the full NIH press release on the normal bacterial makeup of the body

Related: Tracking the Ecosystem Within UsWhat Happens If the Overuse of Antibiotics Leads to Them No Longer Working?Antibacterial Products May Do More Harm Than GoodAntibiotics Too Often Prescribed for Sinus Woes

Human Gene Origins: 37% Bacterial, 35% Animal, 28% Eukaryotic

The percent of human genes that emerged in various stages of evolution: 37% bacterial, 28% eukaryotic, 16% animal, 13% vertebrate, 6% primate. The history that brought us to where we are is amazing. Eukaryotes include animals, plants, amoebae, flagellates, amoeboflagellates, fungi and plastids (including algae). So eukaryotic genes are those common to us and other non-animal eukaryotes while those classified as animal genes are shared by animals but not non-animal eukaryotes.

We are living in a bacterial world, and it’s impacting us more than previously thought by Lisa Zyga

Bacterial signaling is not only essential for development, it also helps animals maintain homeostasis, keeping us healthy and happy. As research has shown, bacteria in the gut can communicate with the brain through the central nervous system. Studies have found that mice without certain bacteria have defects in brain regions that control anxiety and depression-like behavior. Bacterial signaling also plays an essential role in guarding an animal’s immune system. Disturbing these bacterial signaling pathways can lead to diseases such as diabetes, inflammatory bowel disease, and infections. Studies also suggest that many of the pathogens that cause disease in animals have “hijacked” these bacterial communication channels that originally evolved to maintain a balance between the animal and hundreds of beneficial bacterial species.

Scientists have also discovered that bacteria in the human gut adapts to changing diets. For example, most Americans have a gut microbiome that is optimized for digesting a high-fat, high-protein diet, while people in rural Amazonas, Venezuela, have gut microbes better suited for breaking down complex carbohydrates. Some people in Japan even have a gut bacterium that can digest seaweed. Researchers think the gut microbiome adapts in two ways: by adding or removing certain bacteria species, and by transferring the desired genes from one bacterium to another through horizontal gene transfer. Both host and bacteria benefit from this kind of symbiotic relationship, which researchers think is much more widespread than previously thought.

We want badly for the message in ‘Animals in a bacterial world,’ to be a call for the necessary disappearance of the old boundaries between life science departments (e.g., Depts of Zoology, Botany, Microbiology, etc.) in universities, and societies (e.g., the American Society for Microbiology, etc.). We also want the message disseminated in college and university classes from introductory biology to advanced courses in the various topic areas of our paper.”

Very cool stuff. This amazing facts scientists discover provide an amazing view of the world we live in and how interconnected we are to other life forms in ways we don’t normally think of.

Related: People’s Bodies Carry More Bacterial Cells than Human CellsMicrobes Flourish In Healthy PeopleTracking the Ecosystem Within UsForeign Cells Outnumber Human Cells in Our BodiesBacteria Beneficial to Human Health

Memory is Stored by Turning on Genes in Neurons (to Alter Connection Between Neurons)

I find these kind of stories so interesting. I really have so little understanding of genes. I knew memory had something to do with altering connections between neurons. I had no idea that required turning on many genes in those neurons. Life really is amazing.

Neuroscientists identify a master controller of memory

When you experience a new event, your brain encodes a memory of it by altering the connections between neurons. This requires turning on many genes in those neurons.

Lin and her colleagues found that Npas4 turns on a series of other genes that modify the brain’s internal wiring by adjusting the strength of synapses, or connections between neurons. “This is a gene that can connect from experience to the eventual changing of the circuit,” says [Yingxi] Lin

So far, the researchers have identified only a few of the genes regulated by Npas4, but they suspect there could be hundreds more. Npas4 is a transcription factor, meaning it controls the copying of other genes into messenger RNA — the genetic material that carries protein-building instructions from the nucleus to the rest of the cell. The MIT experiments showed that Npas4 binds to the activation sites of specific genes and directs an enzyme called RNA polymerase II to start copying them.

“Npas4 is providing this instructive signal,” Ramamoorthi says. “It’s telling the polymerase to land at certain genes, and without it, the polymerase doesn’t know where to go. It’s just floating around in the nucleus.”

When the researchers knocked out the gene for Npas4, they found that mice could not remember their fearful conditioning. They also found that this effect could be produced by knocking out the gene just in the CA3 region of the hippocampus. Knocking it out in other parts of the hippocampus, however, had no effect.

One of the things I aim to do in 2012 is read a few more books on biology and genes. I find it incredible what are genes actually are doing to allow us to live our lives. And I am also very ignorant on the whole area. So hopefully I can have some fun next year learning about it.

Related: Epigenetic Effects on DNA from Living Conditions in Childhood Persist Well Into Middle AgeAntigen Shift in Influenza Viruses8 Percent of the Human Genome is Old Virus GenesBrain Reorganizes As It Learns Math

Epigenetic Effects on DNA from Living Conditions in Childhood Persist Well Into Middle Age

Family living conditions in childhood are associated with significant effects in DNA that persist well into middle age, according to new research by Canadian and British scientists.

The team, based at McGill University in Montreal, University of British Columbia in Vancouver and the UCL Institute of Child Health in London looked for gene methylation associated with social and economic factors in early life. They found clear differences in gene methylation between those brought up in families with very high and very low standards of living. More than twice as many methylation differences were associated with the combined effect of the wealth, housing conditions and occupation of parents (that is, early upbringing) than were associated with the current socio-economic circumstances in adulthood. (1252 differences as opposed to 545).

I find Epigenetics to be a very interesting area. My basic understanding as I grew up was that you inherited your genes. But epigenetics explores how your genes change over time. This has been a very active area of research recently. Your DNA remains the same during your life. But the way those genes are expressed changes.

I don’t know of any research supporting the idea I mention in this example, but, to explain the concept in a simple way: you may carry genes in your DNA for processing food in different ways. If you have very limited diet the way your body reacts could be to express genes that specialize in maximizing the acquisition of nutrition from food. And it could be that your body sets these expressions based on your conditions when young; if later, your diet changes you may have set those genes to be expressed in a certain way. Again this is an example to try and explain the concept, not something where I know of research that supports evidence for this example.

The findings by these universities, were unfortunately published in a closed way. Universities should not support the closing of scientific knowledge. Several universities, that support open science, require open publication of scientific research. It is unfortunate some universities continue to support closed science.

The research could provide major evidence as to why the health disadvantages known to be associated with low socio-economic position can remain for life, despite later improvement in living conditions. The study set out to explore the way early life conditions might become ‘biologically-embedded’ and so continue to influence health, for better or worse, throughout life. The scientists decided to look at DNA methylation, a so-called epigenetic modification that is linked to enduring changes in gene activity and hence potential health risks. (Broadly, methylation of a gene at a significant point in the DNA reduces the activity of the gene.)

Related: DNA Passed to Descendants Changed by Your LifeBlack Raspberries Alter Hundreds of Genes Slowing CancerBreastfeeding Linked to More Intelligent Kids

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Synthetic Biologists Design a Gene that Forces Cancer Cells to Commit Suicide

Killing a cancer cell from the inside out

To create their tumor-killing program, the researchers designed a logic circuit — a system that makes a decision based on multiple inputs. In this case, the circuit is made of genes that detect molecules specific to a type of cervical cancer cell. If the right molecules are present, the genes initiate production of a protein that stimulates apoptosis, or programmed cell death. If not, nothing happens.

Because the genes used to create the circuits can be easily swapped in and out, this approach could also yield new treatments or diagnostics for many other diseases, according to Ron Weiss, an MIT associate professor of biological engineering and one of the leaders of the research team. “This is a general technology for disease-state detection,” he says.

the researchers created a synthetic gene for a protein, called hBax, that promotes cell death. They designed the gene with two separate safeguards against the killing of healthy, non-HeLa cells: It can be turned off by high levels of microRNAs that are ordinarily low in HeLa, and can also be deactivated by low levels of microRNAs that are normally plentiful in HeLa. A single discrepancy from the target microRNA profile is enough to shut off production of the cell-death protein.

If all microRNA levels match up with the HeLa profile, the protein is produced and the cell dies. In any other cell, the protein never gets made, and the synthetic genes eventually break down.

More very cool research. It is exciting to see how much can be done when we invest in science and engineering research. Of course the path from initial research to implemented solutions is long and complex and often fails to deliver on the initial hopes. But some remarkable breakthroughs achieve spectacular results that we benefit from every day.

Related: Cancer VaccinesResearchers Find Switch That Allows Cancer Cells to SpreadGlobal Cancer Deaths to Double by 2030Cloned Immune Cells Clear Patient’s Cancer

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