Sex, Life, Death and the Scientific Method

Why do women live longer than men? That question caught my eye when it popped up in my twitter feed, so I followed the link over to a podcast on the Scientific American website.  Before I could even listen to the podcast I noticed that someone posted the following in the comments section:

"I have a possible explanation of why women live longer than men. Men have an XY sex chromosome while women have an XX sex chromosome. This results in both the greater potential for genetic (chromosomal) variation in men that successfully adapts to the environment (and passes the same to succeeding generations) and genetic mutation which results in both chromosomal deleterious deterioration and maladaptation that results in early cell and male human death (and which, therefore, is less likely to pass the deleterious chromosomal variation to succeeding generations). Thus, men, in general, live shorter lives than women because their environmental success has a significantly more profound influence on how appropriate their genetic make up is to adapting to the same. At the same time, men's genetic make up (XY vs XY) is much more susceptible to deleterious genetic aberrations and maladaptations. Of course, the aforementioned is simply theory."

Viewed through the lens of science, this suggestion makes a great hypothesis, so I thought I'd mention it here (total avoidance behavior, by the way - I've got a thesis to write!!). So why is it a good hypothesis? Because a good hypothesis is (among other things) one that suggests practical ways to challenge it's own validity. Using claims that logically follow from the original hypothesis, we can test those claims with experimental or observational data. In this case, our hypothesis is:

XY individuals lead shorter lives (on average) than do XX individuals because (on average) mutations in either the X or Y chromosome have the potential to result in greater phenotypic change.

So what statements or predictions follow from this claim that we can test empirically? How can we try and falsify this idea? In this case, we need to look beyond humans for the answer to that questions...

Now, before we get all myopic and try and pretend all gender differences in all species boil down to this single hypothesis, we should be mindful of the myriad other differences between males and females that contribute to longevity.  For example, in humans...

But hey, nothing in science would ever get done if we didn't take things one step at a time, so lets take a closer look at the hypothesis at hand.

I just so happens that here are other mechanisms of sex determination than the XX/XY system found in humans and other mammals. Many reptiles and birds, for example, have a ZW/ZZ system where unlike the mammalian system, ZZ=male and ZW=female. So putting this fact together with our summary statement above, we've come up with a quick prediction: that in birds and reptiles with ZW/ZZ sex determination, the females should be the shorter-lived sex.

So what's the story in birds?  A quick web search (sorry - I need to get back to work!) revealed that people have actually considered this hypothesis before and done some of the leg work for us already.  For example, in Austad 2006 (reference below) the author writes:

Another way to investigate the hypothesis that the sex possessing the heterogametic chromosomes is going to be longer-lived is to consider birds, because the sex-chromosome situation is reversed compared with mammals. In birds, it is the female that has 1 short and I long sex chromosome, and therefore does not have the backup of the 2 long sex chromosomes (the Z chromosomes) that the male has. The prediction is that if heterogametic sex is a key factor, then male birds should be longer-lived. In fact, in 3 species of birds,  including budgerigars, zebra finches, and Japanese quail, males outlive females, at least in captivity. For every bird species that I have been able to find in which there is good captive data, males outlive the females. Certainly, this is provocative evidence that would seem to favor the heterogametic sex hypothesis. It is of concern, however, that in some avian species, the female has been reported to outlive the male, but all of these reports were from field studies and are thus difficult to interpret for the reasons discussed previously.

I like the heterogametic sex hypothesis because it is biologically interesting. Unfortunately, that does not mean it is true.  There are some problems with this hypothesis that can be illustrated with Brandt's bat, a small bat that weighs about 7 grams and is a third to a quarter the size of a mouse... [author cites a study that found males appeared to be longer lived.]  We just don't know the answers to these questions because we do not know what the underlying physiology is and whether behavioral differences or physiological differences are responsible for this remarkable observation in a Siberian cave.

We are also aware of some mammals in which the males are significantly longer-lived than the females; we have very good captive data for 2 of these species, the guinea pig and the golden hamster. In both species, the males live substantially longer than the females, thereby contradicting the heterogametic sex and estrogenic hypotheses. Again, this is a problem in a general biological sense; it may very well be that one of these hypotheses is absolutely valid for humans but is just not generalizable to the rest of mammals. I would like a general explanation, and that is something we currently do not have.

So strictly speaking, this hypothesis is toast. Plenty of evidence to the contrary is floating around out there, so we can rule it out as an accurate summary of reality. But does that mean we just throw it out? Heck no!  Instead of viewing hypotheses as a black and white question of "true vs. false," we instead seek to refine the statement (if possible) and make a new hypothesis consistent with this new information.

For example, we may include the caveat that other processes might matter more in some species than accumulated deleterious effects, thus restricting the kinds of organisms we can apply our hypothesis to.  Also, better experimental investigations could better challenge the core idea behind our hypothesis: genetic changes in the sex chromosomes and their resulting phenotypic changes.  As you can see, all this hypothesizing and testing can snowball into an entire career of work fairly quickly.

As much as I'd love to continue probing the world of longevity and gender genetics, I'm afraid I've got work to do (thesis work!). If I've piqued your interest and you turn up any other interesting studies on the subject, feel free to share in the comments below.

References

• Austad, Steven N. 2006 "Why women live longer than men: Sex differences in longevity." Gender Medicine 3(2). doi:10.1016/S1550-8579(06)80198-1

Templeton Foundation Talk Tomorrow in Columbus

Since 2006, the Ohio State University has hosted an annual discussion of religion, science and evolution entitled The Intersection of Science and Faith. It's funded by the John Templeton Foundation (JTF) and this year's discussion will be happening tomorrow (Wednesday) at 7pm at COSI in Columbus. Attendance is free, but registration is required to attend.

If you're in town, you should check it out!

Here's the announcement from the COSI calendar (PDF flier here):

Beyond Belief: Is Religion in Our Genes?
October 13, 2010 - October 13, 2010
Wednesday, October 13, 2010 (7pm-9pm)

Supported by a grant from the John Templeton Foundation

Join COSI and moderator Neal Conan, senior host of the National Public Radio talk show, Talk of the Nation, for a lively panel discussion with Andrew Newberg, MD, Director of Clinical Nuclear Medicine, Director of NeuroPET Research, University of Pennsylvania, and author of "Why God Won't Go Away: Brain Science and the Biology of Belief," and Nicolas Wade, New York Times science writer and author of "Before the Dawn," and "The Faith Instinct." This program takes place inside the WOSU@COSI Studios on COSI's Level 1.

Register: RSVP by calling 614.228.2674, registration is required.

Cost: This event is free

Admission: Free; registration is required - please call 614.228.2674 to RSVP.

Sounds interesting, right?  But what might we expect from the discussion? What's the John Templeton Foundation?  Who are the speakers?  To answer these questions, lets take a closer look at the speakers and the funding source.

Monday Mammal #9: Marsh Rice Rat

Many of this week's Monday Mammal, the Marsh Rice Rat (Oryzomys palustris), have likely perished recently as oil from the spill off of the Louisiana coastline has been recently been penetrating the coastal salt marshes.  Fortunately, these little rodents aren't limited to these coastal marshes (unlike some species), and should (as a species, at least) persist beyond the recent disaster.

Figure 1:  "Oryzomys palustris - lower image is silvery subspecies O. p. argentatus of Florida Keys

Credit: painting by Ron Klinger from Kays and Wilson's Mammals of North America,
© Princeton University Press (2002)"  [Source]

This rather broad ranging American native was first described in 1837 from a specimen taken in the north of their range in Salem Co. New Jersey.  They are semi-aquatic, mostly nocturnal omnivores and are found primarily in coastal (salt water) and interior (fresh water) marshes.  Like many (most?) other species, their distribution hasn't always been restricted to their current range.  Despite being endemic to the south eastern U.S. their ancestors likely trace back to central and South America.

These rats belong to the subfamily Sigmodontinae, the South American rats and mice. While there is one other species of Oryzomys that makes it up into North America -- the Coues's Rice Rat (O. couesi) which occurs in southern Texas -- the other species in the genus Oryzomys all appear to occur further south.

Oh, and here's one of those random facts you just don't find in species accounts any more -- just in case you were wondering how different these rats are from their domestic cousins. Unlike domestic rats, Marsh Rice Rats have 27 pairs of autosomal chromosomes plus two sex chromosomes for a grand total of 56 chromosomes...

[Source]

Hmm... this could make for a nice little pop quiz!  Do you know how many chromosomes do we humans have?

Summary of Cancer Research Facts

Over at the Respectful Insolence, Orac has shared a video produced by the American Association for Cancer Research which includes a wealth of information about the current state of cancer research.  You to read Orac's take on the video if you're interested in the topic (though do ignore his unappreciative take on the soundtrack!).

What a remake of this video will look like 5, 10 or 15 years from now is anyone's guess -- but one thing is certain: it'll take a whole lot of money, manpower, technological innovation, and sound science if we're to continue to make progress in treating and preventing cancer.

4000 year old human genome from Greenland

There's a nice post over at John Hawk's Weblog on the recent news that a group of researchers sequenced nearly 80% of the genome from a human that lived in Greenland nearly 4000 year ago.  The paper can be read in full online via Nature (PDF). If you're going to read the paper, do check out John's post for his commentary on the open and collaborative nature of this work.

Behold... the human brain!

"...one of science's final frontiers ... the human brain."

Tonight, while sharing a late night bowl of ice cream, my wife and I happened upon the fourth episode of the Brain Series by Charlie Rose. It pretty much poked all my science-dork buttons, so I of course had to run right over to the computer and put up a post telling you to watch the series - it's cool stuff!!

You can see all available episodes of the series here. The discussions cover some interesting and important topics. I'm already excited for next episode on brain development and child learning.

I haven't watched them all yet, but the series seems to touch on a variety of topics related to what our brains do and how they do it. The format is the usual scene: a table full of experts moderated by Charlie Rose. If anything, it's a great chance to hear a handful of experts discussing some of the latest insights into common brain disorders like autism/ASD, schizophrenia, and depression. There is also a fair bit of discussion related to brain development during the first few years of life, which should be of interest to parents.

For more info, check the links above and your local PBS listings.

How do you sequence a genome?

Have you ever wondered how genes or whole genomes are sequenced, or how DNA sequencing plays into our understanding of how life has evolved here on Earth??

Without getting in to all the details, here's some great video footage that provides a glimpse into this world. Additionally, the video includes discussion (towards the end) of the role science plays in society and what that implies for the future of our species, and life on earth. At any rate - I think it's well worth watching despite the length of the video!

Here, Richard Dawkins is interviewing Craig Venter while getting a tour of his sequencing facilities - an impressive example of "industrial biology" driving the cutting edge of science. Even in the first 15 minutes or so, you get a feel for how much heavily these sequencing technologies rely on contributions from many scientific fields, including mathematics, statistics, computer science, chemistry and engineering.



If you pay attention, you can also glean some other interesting tidbits of information... For example, individual humans seem to differ not by the tenths of a percent we've been told, but probably more like 1% or 2%. Humans and chimps?? Well, we differ by more than the 1.2% so often quoted on such public forums as youtube -- apparently the difference is "more like 5-6%" (not to mention our differing number of chromosomes, etc.).

But, getting back to the original question: How do you sequence a genome?

To get a feel how this sort of sequencing works, let's first consider the 23 chromosome pairs in a single cell, all together holding a little over 6 billion DNA base pairs, which we could imagine lining up end-to-end as one single sequence - for example a book with 46 chapters each corresponding to an individual chromosome.

Next, imagine taking millions and millions of random snapshots of that DNA, each snapshot capturing only a very short sequence (e.g. a few hundred base pairs or maybe spanning a page or two if we stick to our "genome-as-a-book" analogy). Taken together, these tiny "snapshot" sequences (actually called "reads") cover the whole genome, with some of those reads overlapping one another. After taking enough snapshots, we know these reads contain all the information in the original genome sequence, but how can we put it all back together?

The answer hinges on the fact that these reads are in many places, overlapping. By using various mathematical and computational methods, all of the pieces can be matched up, eventually yielding the full genome sequence.

You can find more details here and here.

Gene regulation in mammalian cells: a complex democracy?

[From Sandwalk]

A (perhaps oversold?) press release entitled "International team cracks mammalian gene control code" is making the rounds, and while maybe a bit overreaching it looks pretty interesting!

For more details, check out this a blurb from Nature Genetics: "FANTOM studies networks in cells: Systems biology boosted by RNA-sequencing consortium" by Heidi Ledford. You can also read the abstracts at the links below (abstracts only - the articles aren't freely available online).

Publication Links:

1. The FANTOM Consortium and the Riken Omics Science Center, The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line. Nature Genetics (2009) doi:10.1038/ng.375
   
2. Taft, R. J. et al. Tiny RNAs associated with transcription start sites in animals. Nature Genetics (2009) doi:10.1038/ng.312
3. Faulkner, G. J. et al. The regulated retrotransposon transcriptome of mammalian cells. Nature Genetics (2009) doi:10.1038/ng.368

Why some love - or hate - Coriander

Opinions are quite varied on whether adding fresh coriander (aka cilantro) to a recipe makes or breaks the dish. Some folks simply love the stuff while others find the herb quite repulsive - often noting a metallic, soapy or otherwise unpleasant flavor (other descriptions of the repulsive taste and/or smell can be found here) a description that seems quite different from how fans describe it. So why the disparity??

Thanks to work by a few diligent and inquisitive scientists, we do know a few things about this love-hate relationship with one of my favorite herbs. Some these discoveries have been stumbled upon while working on more important issues while others come more focused and direct studies of the plant.

Coriander (aka cilantro or Chinese parsely) is the common name of the plant Coriandrum sativum, a member of the carrot family Apiaceae or Umbelliferae. The young leaves are the herb called cilantro, while the older leaves and seeds are called coriander - although the herb is commonly referred to by both names. For some interesting Coriandrum chemistry, check out the chapter on the chemical properties of the herb starting on page 190 of Chemistry of Spices, available through Google Book Search. Unfortunately the book doesn't have much info on why some find the herb so revolting...

So why the divide? According to work by folks like Charles Wysocki from the Monell Chemical Senses Center it seems there are very likely some genetic factors that contribute to the preference. This based on preliminary work comparing pairs of twins with non-twins - if its heritable, pairs of identical twins will share a preference more so than fraternal twins, with the lowest proportion of shared preferences seen between non-twin siblings.

Initially some believed the cilantrophiles among us were unable to taste or smell some particularly offensive chemical found in the plant. This is a reasonable hypothesis, and is in line with similar phenomena such as the more common example involving asparagus (although I recently learned that producing and being able to smell the offending byproduct in this case are two separate issues).

With cilantro, it turns out this notion is a bit off. There does seem to be a difference in smelling (and tasting) ability among the cilantro lovers and haters among us, but according to this essay by Josh Kurz on the NPR website, the smell some folks are missing out on is not a foul one, but that pungent lemony smell so adored by cilantro lovers. If you are among those who hate cilantro, you really might not know what you're missing!

Given the descriptions I have heard and read, there may indeed be some other more unpleasant smells that are only detectable by the unfortunate few. This could simply be because the compounds that smell so good to some are themselves the culprits, being pleasant to some and repulsive to others. The GC anecdote in Josh Kurz's article suggests otherwise, however. So the two smells/tastes are indeed caused by two different chemicals. Unfortunately the essay doesn't mention whether or not researchers Wysocki and Preti were also able to smell the unpleasant compounds.

Interestingly, this information doesn't show up on ihatecilantro.com!

So will the world be a better place for knowing all this? Probably not, but I can already imagine someone slaving away for Monsanto trying to get rid of the repulsive compounds - after all, there is a big difference between "tastes bad" and "tasteless"!