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The Amazing Reality of Genes and The History of Scientific Inquiry

Posted on March 4, 2017  Comments (4)

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 Uncertainty – Human Gene Origins: 37% Bacterial, 35% Animal, 28% Eukaryotic – Unexpected Risks Found In Editing Genes To Prevent Inherited Disorders – Epigenetic Effects on DNA from Living Conditions in Childhood Persist Well Into Middle Age – Why Don’t All Ant Species Replace Queens in the Colony, Since Some Do

Parasite Evolved from Cnidarians (Jellyfish etc.)

Posted on November 22, 2015  Comments (0)

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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Cancer Rates Consistent Across Species Instead of Increasing Due to Body Mass

Posted on October 12, 2015  Comments (1)

It would seem sensible to think cancer should be more prevalent in species with a huge number of cells, and thus more cells to become cancerous. But cancer risk doesn’t increase in this way. This interesting, open source paper, sheds some light on what is behind this.

Solutions to Peto’s paradox revealed by mathematical modelling and cross-species cancer gene analysis

Whales have 1000-fold more cells than humans and mice have 1000-fold fewer; however, cancer risk across species does not increase with the number of somatic cells and the lifespan of the organism. This observation is known as Peto’s paradox. How much would evolution have to change the parameters of somatic evolution in order to equalize the cancer risk between species that differ by orders of magnitude in size? Analysis of previously published models of colorectal cancer suggests that a two- to three-fold decrease in the mutation rate or stem cell division rate is enough to reduce a whale’s cancer risk to that of a human. Similarly, the addition of one to two required tumour-suppressor gene mutations would also be sufficient.

We surveyed mammalian genomes and did not find a positive correlation of tumour-suppressor genes with increasing body mass and longevity. However, we found evidence of the amplification of TP53 in elephants, MAL in horses and FBXO31 in microbats, which might explain Peto’s paradox in those species. Exploring parameters that evolution may have fine-tuned in large, long-lived organisms will help guide future experiments to reveal the underlying biology responsible for Peto’s paradox and guide cancer prevention in humans.

Elephants in Kenya

Elephants in Kenya by John Hunter. See more photos from my trip to Kenya.

In another way it would make sense that large animals would have hugely increased risks of cancer. As they evolved, extremely high cancer rates would be a much bigger problem for them. Therefore it wouldn’t be surprising to find they have evolved a way of reducing cancer risks.

Despite these limitations, we found genes that have been dramatically amplified in specific mammalian genomes, the most interesting of which is the discovery of 12 TP53 copies in the genome of the African elephant. We subsequently cloned those genes and identified 19 distinct copies of TP53 in African elephants and 15–20 in Asian elephants [1]. Another potential lead for solving Peto’s paradox is MAL, which is found to have eight copies in the horse genome and two in microbat. This could be an example of convergent evolution where a large animal (horse) and a small, long-lived animal (microbat) both evolved extra copies of the same gene to overcome their increased risk of cancer. Further analysis and experimentation would need to be performed to determine the function of these copies and whether or not they provide enhanced suppression of carcinogenesis.

The researchers have found an interesting potential explanation for how that has been accomplished.

Related: The Only Known Cancerless Animal (the naked mole rat) – Webcast of a T-cell Killing a Cancerous Cell – Researchers Find Switch That Allows Cancer Cells to Spread – Cancer Vaccines

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

Posted on March 22, 2014  Comments (0)

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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Go Slow with Genetically Modified Food

Posted on August 3, 2013  Comments (2)

My thoughts on Genetically Modified Organisms (GMO), specifically GM foods, basically boil down to:

  • messing with genes could create problems
  • we tend to (and especially those seeking to gain an advantage tend to – even if “we” overall wouldn’t the people in the position to take aggressive measures do) ignore risks until the problems are created (often huge costs at that point)
  • I think we should reduce risk and therefore make it hard to justify using GMO techniques
  • I agree occasionally we should do so, like it seems with oranges and bananas.
  • I agree the practice can be explained in a way that makes it seem like there is no (or nearly no) risk, I don’t trust we will always refrain from stepping into an area where there is a very bad result

Basically I would suggest being very cautious with GMO. I like science and technology but I think we often implement things poorly. I think we are not being cautious enough now, and should reduce the use of GMO to critical needs to society (patents on the practices need to be carefully studied and perhaps not permitted – the whole patent system is so broken now that it should be questioned at every turn).

Antibiotic misuse and massive overuse is an obvious example. We have doctors practicing completely unjustified misuse of antibiotics and harming society and we have factory farms massively overusing antibiotics causing society harm.

The way we casually use drugs is another example of our failure to sensibly manage risks, in my opinion. This of course is greatly pushed by those making money on getting us to use more drugs – drug companies and doctors paid by those companies. The right drugs are wonderful. But powerful drugs almost always have powerful side effects (at least in a significant number of people) and those risks are multiplied the more we take (due to interactions, weakness created by one being overwhelmed by the next etc.). We should be much more cautious but again we show evidence of failing to act cautiously which adds to my concern for using GMO.

I love antibiotics, but the way we are using them is endangering millions of lives (that is a bad thing). I don’t trust us to use science wisely and safely. We need to more consciously put barriers in place to prevent us creating massively problems.

Related: Research on Wheat Rust – The Avocado – Overfishing, another example of us failing to effectively cope with systemic consequences

Huge Human Population Boom 40,000 to 50,000 Years Ago

Posted on March 14, 2013  Comments (1)

Interesting open access paper on looking at the Y-chromosome to explore our ancestry: A calibrated human Y-chromosomal phylogeny based on resequencing. I can’t understand all the details but the basic idea isn’t that complicated. It is interesting to see these details as are the conclusions that can be drawn: that we had a big explosion of human population o 41,000–52,000 years ago.

This population explosion occurred, between the first expansion of modern humans out of Africa 60,000 to 70,000 years ago and the Neolithic expansions of people in several parts of the world starting 10,000 years ago.

“We think this second, previously unknown population boom, may have occurred as humans adapted to their new environment after the first out-of-Africa expansion,” says Dr Qasim Ayub, lead author from the Wellcome Trust Sanger institute. “We think that when humans moved from the horn of Africa to Asia, Australia and eventually Europe, they remained in small groups by the coasts. It took them tens of thousands of years to adapt to the mountainous, forested surroundings on the inner continents. However, once their genetic makeup was suited to these new environments, the population increased extremely rapidly as the groups travelled inland and took advantage of the abundance of space and food.”

The work highlights how it is now possible to obtain new biological insights from existing DNA sequencing data sets, and the value of sharing data. The majority of the DNA information used for this study was obtained from freely-available online data-sets.

This is the first time researchers have used the information from large-scale DNA sequencing to create an accurate family tree of the Y chromosome, from which the inferences about human population history could be made.

Full press release

Related: Laser Tool Creates “blueprints” of Archeology Sites – HHMI on Science 2.0: Information Revolution – Scientists crack 40-year-old DNA puzzle

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

Posted on February 17, 2013  Comments (3)

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.
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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.
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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 Cells – Microbes Flourish In Healthy People – Tracking the Ecosystem Within Us – Foreign Cells Outnumber Human Cells in Our Bodies – Bacteria Beneficial to Human Health

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

Posted on October 26, 2011  Comments (5)

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 Life – Black Raspberries Alter Hundreds of Genes Slowing Cancer – Breastfeeding Linked to More Intelligent Kids

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I Always Wanted to be Some Sort of Scientist

Posted on October 17, 2011  Comments (1)

A nice simple post by a soon to be Dr. of Genetics and Molecular Biology on what being a scientist is like for her. I like her take, which I think is much more accurate than some of the generalities people use. The main reason people (men or women) become scientists because they want to be scientists.

photo of almost-Dr. Caitlin

Photo the almost-Dr. Caitlin

The truth is science requires you to be social. We share ideas, techniques, and equipment. A good scientist knows her limitations and uses someone else’s expertise when her own is not enough. The modern scientist communicates not only through conferences and journals, but also through blogging and Facebook.
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When a non-scientist (usually my parents or some other close relative) asks me about what I do, they inevitably want to tie it back to how I’m curing a disease and saving the world. I am not curing a disease or saving the world.

I study science because it’s cool. I study basic science — asking questions for the purpose of learning the answer. That doesn’t mean what I do isn’t important. Lots of ground-breaking medical advances have been made just because someone asked a question no one else thought to ask.
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To all you ladies fighting the good fight in other fields, keep at it, because the numbers are going up for women with advanced degrees.

I’ve always wanted to be some sort of scientist. When I was in elementary school I wanted to be a paleontologist because dinosaurs are awesome (and so was “Jurassic Park”). When I was 11, I read the Hot Zone and knew I wanted to be a biologist. Though there were times that I flirted with the Dark Side, i.e., medical school, but mostly only because when my teachers figured out I was good at science they said go to medical school. No one even suggested becoming a scientist.

Great stuff. Good Luck, Caitlin.

Related: Movie Aims to Inspire College Students With Tales of Successful Minority Scientists – Kids on Scientists: Before and After Talking to Real Live Scientists – Women Choosing Other Fields Over Engineering, Math, Physics and Computer Science

Most Genes? A crustacean the size of a grain of rice

Posted on February 8, 2011  Comments (4)

photo of Daphnia, a crustacean

“Daphnia are ubiquitous in freshwater ponds and lakes and are often used to assess the health of ponds. Since the creature is so well studied by ecologists, knowing its genetics should reveal a lot about how genes respond to different environments.

The first scientists to describe Daphnia thought they were a kind of flea because they assumed the red color came from sucking blood as fleas do. It turns out they’re not bloodsuckers – they’re blood makers. Daphnia have genes that make hemoglobin, so when the animal is stressed out, those genes switch on and the animal looks red.

In fact Daphnia have an astonishingly large number of genes. “We count more than 31,000 genes,” says [John] Colbourne. By comparison, the human genome has more like 23,000 genes. If Guinness tracks such things, Daphnia would hold the record for the most genes of any animal studied to date.

“Many of those genes – we estimate around 35 percent of them – are brand new to science,”

Daphnia can grow its own spear and helmet when threatened by an attacker

Related: Our Genome Changes as We Age – Amazing Designs of Life – One Species’ Genome Discovered Inside Another Species – Bdelloid Rotifers Abandoned Sex 100 Million Years Ago

Boa Constrictor Gives Birth to Clones

Posted on November 3, 2010  Comments (0)

Snake gives ‘virgin birth’ to extraordinary babies

A female boa constrictor snake has given birth to two litters of extraordinary offspring. Evidence suggests the mother snake has had multiple virgin births, producing 22 baby snakes that have no father. More than that, the genetic make-up of the baby snakes is unlike any previously recorded among vertebrates, the group which includes almost all animals with a backbone.
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“All offspring are female. The offspring share only half the mother’s genetic make-up,” he told the BBC.
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Humans for example have X or Y sex chromosomes; females have two X chromosomes and males have a combination of an X and a Y chromosome. In place of X and Y, snakes and many other reptiles have Z and W chromosomes.

In all snakes, ZZ produces males and ZW produces females. Bizarrely, all the snakes in these litters were WW. This was further proof that the snakes inherited all their genetic material from their mother, as only females carry the W chromosome.

“Essentially they are half clones of their mother,” says Dr Booth. That is because the baby snakes have inherited two copies of one half of their mother’s chromosomes, including one W chromosome.
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More astonishing though, is that no vertebrate animal in which the females carry the odd sex chromosome (in this case the W chromosome) has ever been recorded naturally producing viable WW offspring via a virgin birth.

“For decades WW has been considered non-viable” says Dr Booth. In such species, all known examples of babies that are the product of parthenogenesis are male, carrying a ZZ chromosomal arrangement.

Related: No sex for all-girl fish species – Virgin Birth for Another Shark Species – Bdelloid Rotifers Abandoned Sex 100 Million Years Ago – World’s Smallest Snake Found in Barbados – Androgenesis