Did inbreeding kill the mammoths? Don't believe everything you hear

Whenever people hear about inbreeding, many think of cousins marrying and having mutant babies. People think of inbreeding as a repulsive idea because our genes want us to reproduce with individuals not closely related to us, to decrease the chance of recessive, deleterious traits killing our offspring.  This would ultimately reduce the fitness of the population, a process called inbreeding depression.

Here's the thing, inbreeding is the mating of pairs who are closely related, genetically.  It can lead to homozygosity, which is when a cell has two identical alleles of the same gene on both homologous chromosomes.  In the punnett square below, the individuals with BB and bb alleles are homozygous for that particular trait.

Homozygosity is not necessarily a bad thing.  It's how some of us end up blonde - because blonde is a recessive trait (not dominant), and a person needs to be homozygous recessive for hair color to end up with blonde hair.  A person heterozygous for hair color would carry one copy of the dominant allele (brown) and one copy of the recessive allele, but would express the dominant allele and be brunette.  In reality, heredity is far more complex than this, what I've described here is a simplification of the process.  A lot of genetic disorders are recessive though.  That means that people can be carriers but not express a disorder.  When two carriers have a child, the child has a chance of being homozygous recessive for that trait, since both parents carry a copy of the allele.  It's the reason why purebred animals often have health problems.

Royal families have historically been inbred to maintain "pure" blood lines.  Because of its isolation, the population of Iceland was also historically inbred.  Inbreeding is never going to lead to mutant children with two heads, or something ridiculous like that, because humans do not carry genes for two heads.  In fact, no animals do.

But inbreeding depression in a population can be a really serious issue.  A new open access paper published this past week suggests that woolly mammoths (Mammuthus primigenius) may have inbred themselves into extinction.  See, there's a strong conservation across vertebrate species for the number of cervical vertebrae, which is typically 7.  There are interspecies variations, just like there are for any other trait, but intraspecies variation is limited.  The most typical variation in vertebral number is the presence of ribs in the seventh vertebra.

It looks like this:


The presence of a cervical rib is, in itself, harmless.  But still, 90% of people born with a cervical rib die before reaching reproductive age, thus presenting a huge selective pressure against cervical ribs.  Cervical ribs are often associated with multiple major congenital abnormalities.  The selective pressure against cervical ribs is thus a selective pressure against the other defects it is often associated with.

Three cervical vertebrae of the woolly mammoth were recently found in the North Sea during infrastructural work, and were donated to the Natural History Museum of Rotterdam.  Two of those three cervical vertebrae contained facets of cervical ribs.  The authors looked through other fossil records to find the prevalence of this trait in other mammoths, and in the closely related extant species of African and Asian elephants.

The authors found that 33% of samples from mammoths contained cervical ribs, compared to 3.6% for the two extant elephant species.  This is a statistically significant finding.  The authors then concluded that, with this high incidence of cervical ribs, coupled with the limited genetic diversity of the time, it is likely that inbreeding is what caused the development of these protrusions.  As you can imagine, the internet went bananas over this.

But I have a serious problem with the methodology of this study.  They looked at a total of 16 samples of mammoth cervical vertebrae, and 28 samples of the cervical vertebrae of extant elephants.  This sample size is too small to be considered valid and to support the generalizations that were made.  Furthermore, data was unavailable for 7 of the 16 samples from mammoths.  So they found 3 cases in 9 samples (33%), and reported this as statistically significant.  To be honest, I don't even understand why they would have reported that they looked at 16 samples, when they really could only measure 9 of them.  This was flagged in the peer-review process.  In fact, another group has recently been reported to have ruled out inbreeding among the dwindling mammoth population altogether.  While I'm not going to deny the findings, I'll reiterate that I think the authors have jumped the gun in terms of generalizing their results, and I think that the way this study was reported has now spread a huge amount of misinformation regarding the extinction of woolly mammoths.

This week in biology/medicine (March 24-30, 2014)

A European group has identified a fossil of a new, whale-like species that filtered plankton, showing that Cambrian ecosystems were closer to modern ecosystems than has been previously thought.

A photographic exploration of the oldest living things in the world.  Not research findings, but worth checking out anyway.

Being underweight is as much of a mortality and health risk as being obese.

Crows understand water displacement at the level of a 5-7 year old child. (Open Access)

Speaking of intelligent animals, goats are pretty smart too. (Open Access)

And a public health win!  Public smoking bans have been linked with substantial reductions in preterm births and asthma-related hospital admissions. (Open Access)

Ever had a migraine just after a stressful event?  Apparently that's normal.

Huntington's-associated neurodegeneration linked to depleted levels of an enzyme (cystathionine gamma-lyase) that makes cysteine.  Shameless self-promotion: if you want to know more about CGL or cysteine metabolism, check out this paper!

And a Dutch hospital used a 3D printer to make a plastic skull, which they then transplanted onto a patient.

Don't hit me with your best shot: self-vaccination against the flu

Well, we may be ramping down flu season up here in the northern hemisphere (if winter EVER decides to go away!), but the idea of self-vaccination against the flu is interesting nonetheless, and will be useful in the future as it continues to develop.

Seasonal flu is an infectious disease caused by a virus, and it is estimated to affect 5-10% of adults, and 20-30% of children.  The seasonal flu causes 3 to 5 million cases of severe illness annually (that's globally, fyi), and up to 500 000 deaths.  The most effective way to avoid getting the flu and spreading it to others is through vaccination.  Now, the way flu vaccines work, is that organizations like the CDC and WHO monitor what flu strains are going around.  While the northern hemisphere is experiencing its flu season, the southern hemisphere is not, and vice versa.  That means that whichever flu strains are going around the southern hemisphere in July are being monitored to try to predict which flu strains will be going around the northern hemisphere in January.  This process involves hundreds of research labs, all testing and identifying flu viruses from infected patients world-wide, year-round.  The WHO then consults with experts on which strains should be covered in the next flu shot.

Vaccination coverage against the flu is actually not as high as they should be, and the reason is not that flu shots are dangerous, but that a lot of people have trouble finding the time (I'm guilty of that this year...).  In the US, annual influenza vaccination coverage hovers around 42%, and in Europe it's about 12% for the general population.  To address low coverage and the costs of annual flu shots, researchers from Atlanta, led by James Norman, hypothesized that microneedle patches could be used to get people to vaccinate themselves.  This may sound like a weird concept, but keep in mind that when you take over-the-counter or prescribed medication in your own home, you are self-administering your medicine.  This self-vaccination would be the same thing.  This is what a microneedle patch looks like:

(source)

These have been used before for cosmetic applications and for hormone delivery, but data generally is not available.  This paper reports a study on the usability and acceptability of these patches for self-vaccination.

All participants were shown how to use the patch, and then self-administered three separate times.  The researchers found that there was a learning curve to self-administering, with the number of insertion sites increasing each time the patches were used.  The insertions were also generally well-tolerated, with only very mild redness and swelling of the skin.  About 51% of the participants who regularly get flu shots said they would be vaccinated against influenza if given the choice of having a microneedle patch instead of a needle and syringe.  Of the participants who don't get flu shots, 30% expressed willingness to be vaccinated if they were offered a microneedle patch, which went up to 38% when they were given the choice to self-administer their vaccine.  That means that almost 1/3 of normally non-vaccinated people would get one with this new method!  Participants were asked to rate the pain level between the use of a microneedle patch and an injection using a needle and syringe.  Microneedle patches scored 10 times lower on the pain scale!  

The most significant predictors of vaccine uptake were beliefs about the convenience and reliability of microneedles, and support for microneedles from doctors and family.  Ultimately, the researchers found that the use of microneedles could improve vaccination coverage in the US from 42% to 65%, which could have a significant impact on reducing hospital admissions, productivity losses, and deaths.  

Obviously this technology isn't ready to be rolled out for the 2014 flu season, but it's an interesting start and could have significant implications in the near future.

Let's talk about (plant) sex, baby!

You'd think with all my thesis studying, I'd have had enough of thinking about how awesome plants are.  But you'd be wrong.

When I was in the second year of my undergrad, I took a class on comparative plant physiology.  For some reason, I found this to be one of the more boring classes ever (until I had to sit through comparative animal physiology....zzzzzzzzzzz).  While studying for a final, one of my roommates told me that I needed to think of it like a soap opera.  Not 30 seconds later, I'm in my room reading about how in angiosperms (flowering plants), the pollen tube (the male reproductive organ) swells and bursts during reproduction.

  

And that is when I realized that plant sex can be quite raunchy.

Like I mentioned in my last plant post, many people do not actually think of plants as having these crazy, complex lives.  But they do, and they compete for mates just like animals do.  A new study published a few days ago in the New Phytologist (which I believe is open access), found that the pollen of milkweed actually use weapons to get an advantage over competitors.

It was previously believed that the only type of sexual selection plants like milkweed could participate in was just sending out massive amounts of pollen, in the hopes that one of those grains would be the first to reach the stigma - a part of the female reproductive organ, it looks like this:

(source)

Pollen is generally captured by the stigma either through the air or by pollinators.  Milkweed pollen develops in a pollen sac (technical term pollinium), which attach to the feet or mouthparts of pollinators, like bees, wasps, and butterflies, who then unknowingly contribute to a no-holds-barred sexual competition between plants.  Two pollinia are attached to form a complex (which is confusingly called a pollinarium).  There are five pollinaria per milkweed plant.  The pollinators pick up one of these complexes, then go off to another flower where they pick up another complex, and so on, and these pollinaria attach to each other like a chain, which is called concatenation, and it looks like this:

(source)

Basically what this diagram is showing you is that once the pollinaria attach, it leaves some pollen sacs more likely to leave their pollen on a stigma than the other pollen sacs.  This study looked at sexual selection in milkweed mediated through physical male interference, like where one pollen sac is located in the chain, and through the effect of physical traits, like the horn-like extensions, that contribute to one pollen sac maintaining its coveted position.

Alright, so the authors, led by Andrea Cocucci, studied four species of milkweed.  They analyzed pollen donation efficiency, and they found that there may be a competition for a "coveted spot" in the chain, but the chance of pollination is pretty similar no matter where the pollen sac is.  This position may only give a slight advantage, but not enough for it to be a sexually selected competitive trait.  Then, the authors looked at these horn-like extensions, called caudicle horns, that prevented concatenation in ancestral species.  

       

(horns)                                                    (no horns)

The horns on the pollinarium make it hard for the pollinaria of other species to attach in a chain.  That pretty much gives that plant a selective advantage over another plant, whose pollinaria allow for concatenation.  

Plants are not typically known to use these types of "weapons" and interference strategies in reproduction the way animals do.  This shows that there is a confrontation process in milkweed plants during reproduction that involves a direct physical interaction, and traits like these horns are an adaptive trait likely evolved from male-male competition in plant reproduction!  This is the first-ever report of an active competitive interaction among pollen before landing on the stigma, and the authors go as far as comparing these horns to those of bucks, who violently compete for mates:

(source)

This study also shows that sexual selection is possible even without the ability to move around, see, and smell.  The only thing that's needed for sexual selection is proximity and physical contact.  

Note: I grabbed most of these figures from the research paper.  If you're going to use them, please cite the original paper

If you're interested in learning about animal sexual selection, I'd suggest checking out Dr. Tatiana's Sex Advice to All Creation.  This was one of my "textbooks" for my biology of sex class in second year, super funny and informative!

This week in biology/medicine (March 17-23, 2014)

Scientist find a new mechanism for how body clocks work - could be used in the future to alleviate the effects of chronic shift work and jet-lag.

The loblolly pine genome has been sequenced - that's a loblolly pine below, it's the largest genome sequenced to-date: over 7 times the size of the human genome! (Open Access)

Can't remember where you put your keys?  Blame your genes.

Paternal age causes widespread alterations in gene expression, especially with those genes associated with inflammation, which is implicated with autism. (Open Access)

HIV viral protein is a neurotoxin associated with memory and learning impairment, even under conditions of limited viral replication. (Open Access)

Half of Americans believe in medical conspiracy theories.  Wow!

Effective leaf mimicry was achieved as early as the Early Cretaceous period.  Fossil of the earliest known stick insect discovered. (Open Access)

(source)

Predicting Human Facial Features From DNA Sequence

Alright, with the emotional rollercoaster of submitting my PhD thesis for defense over, and with my second dose of caffeine hitting my bloodstream, it's time to talk some science.

Just this morning, I came across a gem of a paper, published two days ago, that may just revolutionize forensic sciences and paleontology/anthropology (and it's open access! Bonus!).  This paper discusses the creation of a 3D model of human faces based only on their genome sequences.  I'm going to be talking about this paper in a forensics context: even though we've sequenced the human genome, generally only a few physical characteristics can be inferred from any DNA left behind at a crime scene.  Before 2012, forensic scientists could derive ethnicity, ancestry, and in some cases hair colour, but that was pretty much it.  In 2012, a Dutch group of researchers reported finding five candidate genes that influenced human face shape, or facial morphology.

Human face and head shape (or the technical term craniofacial shape) is determined during embryonic development through a series of precisely-timed gene expressions and interactions.  Then, as humans grow and develop, environmental factors and hormones continue to affect facial development.  Part of the reason why identifying the genes involved in human facial morphology has been so difficult is because through the use of genome-wide association studies, we've been trying to define facial development as univariate (meaning it only has one set of variables that define it), rather than the mutlivariate trait that it really is.  But this American group, led by Peter Claes, used a novel method that combined a bunch of different 3D modeling and gene analysis procedures, to look at between-population facial variation using participants with mixed West African and European ancestry from North America, Brazil, and Cape Verde.

The researchers used SNP (pronounced snip) genotyping to identify variance in the gene sequence of participants. SNPs are single nucleotide polymorphisms, which means that they are variations in the sequence of a gene at a single point in the DNA region being observed.

This may seem like it's just a tiny, insignificant change, but SNPs are actually responsible for the majority of genetic variation between humans, and are hugely important in the development of disease, and in response to pathogens, vaccines, and drugs.  In a human genome, there are many many SNPs, no one has just one.  They are also important in crop and livestock breeding, since they introduce the genetic variation that farmers and scientists select for (or against).  In my lab, I tried to work out a really interesting way to use SNPs to identify gene copy number, as an alternative to using Southern blots.  But that's a story for another day (unless it never gets published).

Anyway, Peter Claes and his colleagues selected 50 genes that were potentially related to craniofacial development, and a set of SNPs that had a high frequency of variation in these genes, to test these for their associations in facial shape variation.


Their method jointly modeled ancestry, sex, and genetic makeup (the technical term is genotype), in order to identify their independent effects on facial development. Once they created their 3D model they had another set of participants come in and look at the faces, and try and discern important characteristics from them.  Ultimately, the researchers found a set of 20 genes that significantly influence facial features, particularly in terms of face length and width, strength of the brow ridge, eye distance, nose width, and philtrum size and shape.  Obviously this is just a start, and there needs to be more study with other populations before this model is generalizable.  But the authors are confident that in 5-10 years, this model will be helpful in the prediction of human faces, especially the effect of other factors (age, temperament, adiposity) on facial features.  The construction of a 3D model of a person's face from DNA left at a crime scene could be used to help identify a suspect - although once apprehended, a sample of their DNA would have to match that found at the crime scene.  At the moment, this technology is too new to be used as evidence in a criminal trial.  Interestingly, this technique can also be used to make detailed facial reconstructions of our ancestors, which hasn't been possible to-date.

Thesis Writing, BRB

Hey science lovers,
I'm just putting some finishing touches onto my thesis to submit this week.  I'll be back with some more science soon.  In the meantime, enjoy this bit of whimsy: