Feeds:
Posts
Comments

Posts Tagged ‘Chromosome’

What are you wired to do?

Posted in Uncategorized, tagged , , , , on December 30, 2010| Leave a Comment »

The Jerk
Image via Wikipedia

If you’ve ever watched Steve Martin’s movie “The Jerk“, you may chuckle at the notion of having a “special purpose”.

Nevertheless, you may have wondered about your own special purpose … what are YOU meant to do?  What are some things that give meaning to YOUR life – you know – social connections (having friends and family)?, a sense of purpose (changing the world)?  a sense of self-control (earning a good wage, being healthy and having a modest home)?  satisfaction that comes from a sense of mastery (playing piano sonatas, perfecting yoga poses)?

Yes, yes, yes and yes … according to this research … these are avenues well worth exploring … keep going!!

Ask your genome, however, and it will surely give you a different answer.  By genome, I mean the long chemical strings of A, G, T, C’s that encode the machinery that constitute YOU – your brain and body.  It may have a different agenda.

The biochemical problem for the genome is that it is so damn unstable.  The long string of A, G, T, C’s has an unfortunate chemical tendency to want to break, slip, loop, slide and in so many other ways come unhinged.  We call this process mutation – and for the most part – its something that f**ks up the lives of perfectly good organisms.  Damn genome instability!

What’s a genome to do?  Apparently, one solution to this problem of mutation and the unfortunate load of mutations that can accumulate within an organism or population of organisms, is to exchange one’s DNA with other similar (but non-mutated) stretches of DNA.  Just ‘cut’ out one stretch and ‘paste’ in another, just like you might ‘cut and paste’ a revised paragraph into an essay you are writing.  No problemo!  Now all those deleterious mutations can no longer continue to pile up in the genome, since they can be cut out, and then new bits of DNA pasted in.  This process is known as genetic recombination.  In humans this process takes place in the reproductive system … its hypothesized to be the reason that sex evolved in the first place.

Yes, the genome loves genetic recombination (which necessitates having male and females who want to, um, get together) to lower the load of deleterious mutations.  What a selfish genome we have (although I’m not complaining)!

OK, so happiness research tells us that we need to have friends, self-direction, purpose, mastery etc …  and the genome tells us we need to have (ahem) sex.  So who’s right?

Check out this article  “Money, Sex and Happiness: An Empirical Study” (referencing “Measuring the Quality of Experience”, Princeton University, 2003).

… among a sample of 1000 employed women, that sex is rated retrospectively as the activity that produces the single largest amount of happiness. Commuting to and from work produces the lowest levels of happiness. These two activities come top and bottom, respectively, of a list of 19 activities.

Hmmm.  Are we a whole lot less sophisticated that we want to admit?  Perhaps.  Its not a simple answer, but interesting to think that amidst all the effort we make to attain health, close relationships, security, inner-peace, etc … at the end of the day … we just want to have sex.

Enhanced by Zemanta

Read Full Post »

Movie star SIRT1 makes for a great body but an old brain

Posted in CREB, SIRT1, tagged , , , , , , , , on July 20, 2010| 2 Comments »

Cinematicode wall
Image by Smeerch via Flickr

As far as science movies go, the new movie, “To Age or Not To Age” seems like a lot of fun.  The interview with Dr. Leonard Guarente suggests that the sirtuin genes play a starring role in the film.  Certainly,  an NAD+ dependent histone deacetylase – makes for a sexy movie star – especially when it is able to sense diet and metabolism and establish the overall lifespan of an organism.

One comment in the movie trailer, by Aubrey de Grey, suggests that humans may someday be able to push the physiology of aging to extreme ends.  That studies of transgenic mice over-expressing SIRT1 showed physiological properties of calorie-restricted (long lived) mice – even when fed ad libitum – suggests that something similar might be possible in humans.

Pop a pill and live it up at your local Denny’s for the next 100 years?  Sounds nice (& a lot like grad school).

Just a few twists to the plot here.  It turns out that – in the brain – SIRT1 may not function as it does in the body.  Here’s a quote from a research article “Neuronal SIRT1 regulates endocrine and behavioral responses to calorie restriction” that inactivated SIRT1 just in the brain:

Our findings suggest that CR triggers a reduction in Sirt1 activity in hypothalamic neurons governing somatotropic signaling to lower this axis, in contrast with the activation of Sirt1 by CR in many other tissues. Sirt1 may have evolved to positively regulate the somatotropic axis, as it does insulin production in β cells, to control mammalian health span and life span in an overarching way. However, the fact that Sirt1 is a positive regulator of the somatotropic axis may complicate attempts to increase murine life span by whole-body activation of this sirtuin.

To a limited extent, it seems that – in the brain – SIRT1 has the normal function of promoting aging.  Therefore, developing “pills” that are activators of SIRT1 would be good for the body, but somehow might be counteracted by what the brain would do.  Who’s in charge anyway?  Mother Nature will not make it easy to cheat her! Another paper published recently also examined the role of SIRT1 in the brain and found that – normally – SIRT1 enhances neuronal plasticity (by blocking the expression of a  micro-RNA miR-134 that binds to the mRNA of, and inhibits the translation of, synaptic plasticity proteins such as CREB).

So, I won’t be first to line up for SIRT1 “activator” pills (such as Resveratrol), but I might pop a few if I’m trying to learn something new.

Enhanced by Zemanta

Read Full Post »

Genes for Down syndrome isolated in mouse model

Posted in DYRK1A, KCNJ6, tagged , , , , , , , , , , , , on December 2, 2009| Leave a Comment »

The human brain is renown for its complexity.  Indeed, while we often marvel at the mature brain in its splendid form and capability, its even more staggering to consider how to build such a powerful computing machine.  Admittedly, mother nature has been working on this for a long time – perhaps since the first neuronal cells and cell networks appeared on the scene hundreds of millions of years ago.  In that case, shouldn’t things be pretty well figured out by now?  Consider the example of Down syndrome, a developmental disability that affects about 1 in 800 children.  In this disability, a mere 50% increase in a relative handful of genes is enough to alter the development of the human brain.  To me, its somehow surprising that the development of such a complex organ can be so sensitive to minor disruptions – but perhaps that’s the main attribute of the design – to factor-in aspects of the early environment whilst building.  Perhaps?

So what are these genes that, in the case of Down syndrome, can alter the course of brain development?  Well, it is widely known that individuals with Down syndrome have an extra copy of chromosome 21.  However, the disorder does not necessarily depend on having an extra copy of each and every gene on chromosome 21.   Rare partial trisomies of only 5.4 million base-pairs on 21q22 can produce the same developmental outcomes as the full chromosome trisomy.  Also, it turns out that mice have a large chunk of mouse chromosome 16 that has the very same linear array of genes (synteny) found on human chromosome 21 (see the figure here).  In mice that have an extra copy of about 104 genes, (the Ts65Dn segment above) many of the developmental traits related to brain structure and physiology are observed.  In mice that have an extra copy of about 81 genes, this is also the case (the Ts1Cje segment).

To focus this line of research even further, the recent paper by Belichenko et al., “The “Down Syndrome Critical Region” Is Sufficient in the Mouse Model to Confer Behavioral, Neurophysiological, and Synaptic Phenotypes Characteristic of Down Syndrome” [DOI:10.1523/JNEUROSCI.1547-09.2009]  examine brain structure, physiology and behavior in a line of mice that carry an extra copy of just 33 genes (this is the Ts1Rhr segment seen in the figure above).  Interestingly, these mice display many of the various traits (admittedly mouse versions) that have been associated with Down syndrome – thus greatly narrowing the search from a whole chromosome to a small number of genes.  20 out of 48 Down syndrome-related traits such as enlargement of dendritic spines, reductions of dendritic spines, brain morphology and various behaviors were  observed.  The authors suggest that 2 genes in this Ts1Rhr segment, in particular, look like intriguing candidates.  DYRK1A a gene, that when over-expressed can lead to hippocampal-dependent learning deficits, and KCNJ6, a potassium channel which could readily drive neurons to hyperpolarize if over-expressed.

Reblog this post [with Zemanta]

Read Full Post »