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Blind cave fish undergo eye exams

Mexican Blind Cavefish (Astyanax mexicanus) at Newport Aquarium

Blind cavefish have plenty to show us

It’s rare for an ancestral species to still be alive at the same time as its descendent species, but one example of this phenomenon is the blind cavefish. As its name implies, it is sightless and dwells in caves in northeastern Mexico. Aboveland, biologists can also find the ancestral species to these fish. The ancestral versions are all sighted, providing a perfect scenario for examining some of the genes involved in eye development and sight.

Warning: Bad pun ahead

Not blind to such opportunities, plenty of investigators have turned to Astyanax mexicanus and its ancestor as an animal model. These researchers focus on a field known as “evo devo,” or evolutionary developmental biology. With species such as A. mexicanus, biologists can examine genetic changes in developmental processes that lead to differences between organisms.

One group reported a few years ago that the rudimentary eye in the blind cavefish stopped developing because of overexpression of a pair of genes in the hedgehog family. The two genes, sonic hedgehog (shh) and tiggy winkle hedgehog (twhh) (evo devo folks have a little too much fun with gene names) influence many developmental processes, and in humans, appropriate shh expression results in the formation of two separate eyes, rather than a single, central eye. These researchers took the ancestral species of A. mexicanus and triggered production of extra shh and twhh during development on only one side of the head. On that side of the head, the fish exhibited arrested eye development as embryos, and the adults had no eye there.

Shh: Pleiotropic effects

Genes like shh have what we call “pleiotropic effects,” meaning that they influence several traits. As it happens, even as the blind cavefish lost sight, they gained in other adaptations to living in the dark, including reduced pigmentation, super-refined taste buds, and the ability to navigate using water pressure changes.

Many mutations + three evolutionary events = one outcome

Investigators also realized that for the 29 different populations of A. mexicanus dwelling caves in Mexico, each group might have a different suite of mutations that led to sightlessness. In other words, mutations in different genes in each population led to the same endpoint of blindness. Researchers knew for certain that sightlessness had evolved at least three times among these separated groups. The fish thus also provide an example of convergent evolution, when similar adaptations arise in separated populations or species because environmental pressures are the same.

The fish also offer a lesson in genetics. In studies of bacterial genetics, we learn about a process called complementation. It starts with mixing together two kinds of bacteria, one that has resistance to one chemical and another with resistance to a second chemical. Bacteria that end up with both genes will have resistance to both compounds, something easily tested by growing them on medium containing the two chemicals. This process is called complementation because the two bacterial gene sets complement one another when combined under these conditions.

Cavefish complementation experiments

Operating on a similar principle, a team of researchers crossed blind cavefish from different geographical areas. They thought that because different genes for sight had changed in different populations, the fish might also exhibit complementation. As predicted, in many cases, the genes of the father complemented the genes of the mother, resulting in a complete suite of genes appropriate for eye development in their offspring. The new fish, instead of experiencing truncated eye development, actually had eyes. The researchers had restored sight to the blind cavefish in a single generation. The effect was most pronounced between populations that were most distant from each other, reflecting the standard thinking that geographical separation often reflects genetic separation.

Fish eye exams

The same researchers also devised a clever test to discern whether or not a fish can see. They immobilized the fish and placed them inside a cylinder with flashing, shifting patterns of stripes in black and white. If the fish could see, their eyes would move with the patterns. Thanks to the blind cavefish, we have an excellent example of pleiotropy, convergent evolution, complementation, and natural selection principles, along with the first-ever test for determining whether or not a fish has sight.

Excerpt from The Complete Idiot’s Guide to College Biology: Mendel

Gregor Mendel achieved success in his religious order in his lifetime and lasting scientific fame after his death.

Mendel and the pea plants

Gregor Mendel used tens of thousands of pea plants to make several accurate observations about inheritance decades before scientists demonstrated any of it with modern techniques. With his plants in an abbey garden, he established two laws of inheritance that reflect directly the events of meiosis, again a discovery that predated confirmation using modern techniques. His brilliance lay in his method and his math.

Math also underlies our calculations of inheritance today, determining probabilities about who will inherit which genes. The associations between genes and the characters they give us are more complex than what Mendel derived from his pea plants. They extend beyond the concept of a single gene to multiple genes and even inheritance linked to entire chromosomes or to mitochondrial DNA.

Devoutly statistical

People may have a hard time wrapping their minds around the real brilliance of Gregor Mendel, the plant-crossing monk. Some students likely walk away from their studies of Mendel and his pea plants with the impression that he got lucky with those plants. But Mendel was not only lucky. He was smart, he knew his plants, and he was a true scientist who understand how to translate the biological underpinnings of his statistical results.

He also was a monk who lived in the St. Thomas Monastery for most of his adult life, where he worked as a teacher and cultivator of plants. It was the peas that would eventually lead to his fame, although Mendel died before the fame that was his due finally came his way.

Mendel’s choice:  observation, not luck

Mendel came to science through a natural inclination and a great deal of training. He always had an interest in science, studying physics and chemistry at a university, and teaching science at the school associated with the monastery. At the abbey, he followed his scientific passions with his studies of variation in pea plants.

Mendel didn’t choose these plants by accident. He knew from experience that they had critical features that made them an excellent choice for his study organism. He could self cross a plant, meaning that he could use a plant’s pollen to fertilize the same plant’s ovule. The pea plants had a set of binary traits, meaning that they were either green or yellow or had either wrinkled or smooth peas, nothing in between, no “blending.” And they had short generation times, meaning that they matured fast and he’d get his results quickly.

29,000 plants

Also, Mendel was a mathematician who could interpret his statistical data. Mendel generated a lot of data, ultimately working with about 29,000 plants to achieve his grand opus on genetics. This opus, entitled “Experiments on Plant Hybridization,” generated almost no attention from other scientists. It remained rarely cited and of little interest for decades until resurfacing in the twentieth century, when scientists began to appreciate its genius.

Why is it a work of genius? Because with nothing in the way of molecular biology tools, with no information about genes or heredity, Mendel used 29,000 pea plants to figure out exactly how parents pass on their traits to offspring. He did it through insight into the organism he chose and his training as a mathematician and scientist. But he also did it because, as is the case with so many of the greatest scientists, he had a single-minded tenacity that led him to spend years studying in headache-inducing detail the minutiae of reproduction in 29,000 plants.

Posthumous scientific fame

Now, Mendel’s work is considered so important that we’ve named an entire portion of the study of genetics after him. We call it Mendelian genetics, the genetics of heredity from parent to offspring. Mendel is now known as the father of genetics.

In spite of scientific fame coming to him only posthumously, Mendel did have a different sort of success in his lifetime. When he died, he was Abbot of his monastery, having dedicated his life to his Augustinian order, his abbey, and, through his pea plants, to science.

Inbreeding in the Darwin dynasty?

Darwin and his wife were first cousins

Charles Darwin married his first cousin, Emma Wedgwood, and his own mother was the product of a marriage between third cousins. Given his insights into the relationship among variation, nature’s choices, and adaptation and his observations of weakening in inbred plants, it is no surprise that Darwin worried about his own family’s consanguinity. Did the inbreeding in the Darwin/Wedgwood families show up in his children?

Is marrying your first cousin really so bad?

Had the Darwin/Wedgwoods only engaged in the first-cousin marriage between Charles and Emma, the outcome would likely not have been serious. A 2002 study reported by the National Society of Genetic Counselors found that having first cousins as parents raises the risk of having a significant genetic defect from 3-4% up to about 4-7%. The group concluded that first cousins planning to reproduce require no more intense genetic counseling than unrelated couples.

Consistent consanguinity, on the other hand

But that study didn’t address serial consanguinity of the kind seen in some European royal houses or in the Darwin/Wedgwood families. And a new analysis reported in BioScience avers that the Darwin offspring did experience the repercussions of such inbreeding. Applying an inbreeding coefficient to calculate whether childhood mortality in the Darwin/Wedgwood family across several generations was related to inbreeding, the authors indeed found an association.

Three of the Darwins’ ten children died at age 10 or younger, one of tuberculosis, one of scarlet fever, and one of an unidentified disease. Studies suggest an association between childhood mortality from bacterial infection and consanguinity, and the Darwin family seems to bear that out. In addition, three of the Darwin children who did live to adulthood experienced lengthy marriages without any children, and such infertility may be another manifestation of homozygous states that interfere with reproduction. A photograph of the youngest Darwin child, Charles, who died in toddlerhood, suggests that the baby had some congenital disorder, although the nature of it remains unclear. Emma Darwin was 48 years old when she gave birth to Charles, so Down Syndrome is one likely explanation.

Successful Darwins

In spite of some of the sad facts of the Darwin family story, a few of his children experienced successes of different kinds. Three of his sons were members of the Royal Society, a long-time Darwin family tradition that skipped over the most famous member of the tribe, Charles himself. And Darwin by any measure of fitness did pretty well: in spite of the loss of three children and the infertility of three children, he nevertheless had several grandchildren.

Did Darwin himself suffer from the effects of inbreeding?

Charles Darwin experienced a variety of chronic health conditions, but they do not necessarily seem to have been related to his family’s consanguineous status. Several theories abound to explain his symptoms, which included digestive and skin problems, but no one knows for certain what afflicted the great naturalist. One of the foremost hypotheses is that he had Chagas disease, occurring after a bug bite on one of his voyages transferred an infectious protozoan that may have permanently damaged the scientist’s gut. Stress seems to have exacerbated the problem, whatever its etiology.

A drug for Fragile X syndrome?

Hopeful news but not peer-reviewed

A new report describes success in a very small trial with a new drug that targets behavioral signs of Fragile X syndrome. This syndrome, which affects about one in every five thousand children, mostly boys, usually involves some form of intellectual disability along with a suite of typical physical characteristics, including large jaws and ears and elongated faces. It is the most common known heritable cause of intellectual disability and has also been associated with autism.

Novartis has been working on an experimental drug targeting some of the behavioral manifestations of Fragile X and has just reported, via interview, positive results from a small trial. Because the results are not public and have not been peer reviewed, the nature of the improvements is unknown, as is the nature of the drug itself. All that is known is that a parameter in the treatment group improved in some, but not all, participants with Fragile X. Also, the drug targets reduction of the synaptic noise that people with Fragile X experience. This reduction in neural background noise, it is thought, may pave the way for more typical neurological development.

Why is the X fragile?

The X chromosome consists of many many genes. Some of these sequences may contain repeats of the same three nucleotides, or letters of the DNA alphabet. For example, a gene section might have 50 repeats of the sequence C-A-G. These trinucleotide repeats, as they are known, are associated with a few well-known disease states when they occur in larger numbers. At a certain low number of repeats, they may have no effect, but when the number of repeats increases, a phenomenon known as trinucleotide expansion, the result can be disease. Huntington’s disease is one well-known disorder associated with trinucleotide expansion, and the general rule is that the more repeats there are, the more severe and/or the earlier the onset of the disorder.

On the X chromosome, where these repeats achieve sufficient numbers to result in Fragile X syndrome, the X chromosome itself looks like it’s literally at a breaking point. This visual fragility is what gave the disorder its name when this chromosome characteristic was discovered in 1969. A parent who carries an X chromosome with relatively few repeats does not have Fragile X, but the gene is in a state known as a premutation. Thanks to various rearrangements and events during cell division, this premutation can expand even in a single generation to sufficient numbers of repeats to cause the disorder in an offspring.

Because the relevant gene is on the X chromosome, Fragile X is an X-linked disorder. It’s more prevalent among males than among females because males receive only one X chromosome. Without the second X chromosome backup that females have, males are stuck with whatever genes–and mutations–are present on the single X chromosome they receive.

What is the autism link?

Fragile X underlies a small percentage of diagnosed cases of autism, between 2 and 6%. Because of the usual genetic complexity underlying autism, Fragile X is also the most common known single-gene cause of autism.

These prematurely reported results have also yielded some speculation that a drug that is effective in reducing background noise and improving behaviors for people with Fragile X might do the same for autistic people, even if their autism isn’t related to Fragile X. With nothing in the way of peer-reviewed findings to consider and results available only via interview, such hopes remain in the purely speculative realm.

For your consideration

Males are born with a single X chromosome. Females have two. The X chromosome has hundreds of genes on it. How is it that women can walk around with a double dose of these genes, or conversely, men can be healthy with a half dose?

Trinucleotide expansion occurs when a trinucleotide repeat sequence expands in numbers of repeats, potentially evolving from a premutation to a full-blown disruption of a gene. What are some possible mechanisms by which this expansion might occur?

In the article related to this report, there is reference to “synaptic noise” and to the idea that a drug might reduce this noise and allow more space for typical development. What do you think “synaptic noise” is, physiologically, and how might a drug target this noise?

The mysterious reproductive life of the giant panda

Photo credit: Mehgan Murphy, Smithsonian’s National Zoo

National Zoo’s giant panda had pseudopregnancy

National Zoo officials announced today that Mei Xiang (link has Panda Cam!), who had been monitored for several months for pregnancy, was not pregnant after all. Instead, she was experiencing a common feature of panda endocrinology, the pseudopregnancy.

Panda pseudopregnancy a common event

How could officials not be sure for months about whether or not the pregnancy was real? Panda pseudopregnancy so perfectly mimics an actual pregnancy that even hormone levels follow those of a real gestation. Staff had been monitoring her by ultrasound and blood testing, and even though ultrasound had yet to show a viable fetus, whether the pregnancy was real or pseudo was not confirmed until the hormones wrote the final chapter.

Pseudopregnancy hormones like pregnancy hormones

Late this month, Mei Xiang showed a drop in progesterone hormone. When hormone levels hit baseline in a possibly pregnant panda, one of two things can happen: a birth, or confirmation of pseudopregnancy. The progesterone decline set the clock on a 24-hour watch to see if Mei Xiang would bear a cub. She didn’t.

Ovulation once a year!

Giant pandas ovulate only once a year. Regardless of whether conception occurs, the female panda will appear pregnant, behave as though she is pregnant, and register the hormone patterns of pregnancy. If conception does not occur in that one annual opportunity, a female panda will almost always enter into a pseudopregnant state. Mei Xiang has done that five times. She’s also experienced a genuine pregnancy, bearing a cub in 2005 that now lives in China as part of a panda breeding program.

Panda soon to be back for public viewing

Mei Xiang has been sequestered during her pseudopregnancy, but her habitat at the zoo will now open again for public viewing. During her pseudopregnancy, her behaviors included reduced activity and appetite. These are now both expected to increase.

For your consideration

Pandas have some unusual life history strategies, including being food specialists and often accidentally suffocating their offspring. And, it appears that many ovulations result in pseudopregnancy. What might be an explanation for why pandas are so prone to entering a pseudopregnant state if conception does not occur? Could the behaviors that accompany the pseudopregnancy have anything to do with it?

In pandas, the hormones of a pseudopregnancy are similar to those of a real pregnancy. What pathways underlie the female’s production of these hormones of pseudopregnancy?

Women can also experience pseudopregnancy, sometimes referred to as “hysterical pregnancy.” It can even involve abdominal distention and in some cases, hormonal changes. What are some of the physiological underpinnings of a pseudopregnancy in women?

Finally, dogs and mice are also known for having pseudopregnancies. Do you think the pressures that result in these pseudopregnancies are similar to those that result in a false pregnancy in the panda? Why or why not?

Can rain make buffalos have boys?

African buffalo shift sex ratios with rain

African buffalos (Syncerus caffer) have more males during the rainy season in Kruger National Park, and it’s not just a random accident of fate. Researchers have found that specific sequences on the Y chromosome are correlated with seasonal differences in birth sex ratios in the buffalo population.

X sperm vs. Y sperm

Does that mean that rain somehow makes buffalos have more boys? Not directly. Instead, it may come down to a DNA-level battle royale involving the Y chromosome. Sometimes, sperm carrying the Y win the race to the egg, while at other times, X-carrying sperm are the victors. These times correlate with higher frequencies of certain sequences, or haplotypes, of the Y chromosome occurring in the population, with one sequence being much more common during the rainy season, when more males are born.

Selfish genes gone rogue

The investigation suggested the existence of a suppressor of Y chromosome success acting during the dry season, when females birthed more females, and a distorter in favor of Y chromosome success in the rainy season, when more males are born. The distorter may shift meiosis in favor of the Y-carrying sperm or disrupt survival of X-carrying sperm. Interestingly, distorters are not considered to act for the benefit of the individual carrying them and are considered “selfish genes.” Suppressors…well…suppress the distorters. The authors refer to these apparent Y chromosome suppressor/distorter regions as sex-ratio, or SR,  genes.

Dry season not a good sperm season

They also noted that during the dry season, buffalo didn’t make as much sperm, and the sperm they did make weren’t as frequently normal looking or very good swimmers. They hypothesize that semen quality may interact with the decreased availability of food in the dry season, leading to drop in Y haplotypes associated with a male-biased sex ratio. The investigative team, whose lead author, Pim van Hooft, is based at Wageningen University in The Netherlands, also suggested that the SR genes may be present in other species, adding a new dimension to the increasingly complex mechanisms of sex ratios in mammals.

For your consideration

1. Sex determination in vertebrates happens in a number of different ways. Some mechanisms don’t involve sex chromosomes at all but instead rely on environmental cues. Find an example of a species that uses environmental cues to determine sex. How can an environmental trigger be similar to a chromosomal trigger as a sex determinant? How do they differ?

2. Many species have life history strategies that involve adjusting sex ratios. What are possible explanations can you find to explain how adjusting sex ratio might benefit a species? How might it be a potentially dangerous gamble?

3. Distorters in general appear to be doing their host individual no favors. Given that fact, what is one explanation for the existence and persistence of suppressors of distorters?

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