The subtlety of life – clever codon usage

Codon usage Here’s a paper from September I haven’t had a chance to comment on.

Zhang et al reported in Science (review, paper – subscription required) how two almost identical protein sequences can have different translational modifications. In this case, β-actin and γ-actin are 98% identical, the differences are marginal and don’t explain why one protein is modified with arginine and the other is not.

The difference is actually quite subtle – there is one amino acid in the protein sequence that is lysine in both proteins, but the codons in the RNA are different. That difference is enough to change the relative translation speed of β-actin so that it rapidly folds and gets arginylated but not degraded as happens in the slower translation of γ-actin. In the end, this affects the relative lifetime of each protein in the cell, leading to differential functions.

That’s so cool.

It seems like every so often, things we view as well understood turn out to have another layer of subtlety built in. For example, differential codon usage is usually considered a synonymous change, nothing momentous. Sure, there’s been studies of codon usage relative to the abundance of corresponding tRNAs and how that might be used to modulate abundance of a protein (a quick Google search revealed some interesting codon-usage papers). But I think this case is novel, differential codon usage actually affecting the post-translational modification of a protein simply by tweaking the speed of translation.

How might we create a codon usage table that takes into account tRNA abundance, contribution to translational speed of different codons, and speed of post-translational processes to be able to model and predict things like the differences between the functions of β-actin and γ-actin.

Also, how prevalent is this subtle effect on post-translational modification and how susceptible is it to breaking and causing trouble in a cell?

image from Science review (found via Google images, mind you)

Co-operative evolution of the immune system in humans?

image from www.flickr.com Lee and Mazmanian, from Caltech, published this great review in Science on microbes in the gut and how different bacteria might have been involved in the evolution of the human immune system.

Link (subscription required): Has the Microbiota Played a Critical Role in the Evolution of the Adaptive Immune System? by Yun Kyung Lee and Sarkis K. Mazmanian

They discuss research that shows different bacteria modulating the maturation and function of different types of T-cells. And this modulation not only affects what happens immunologically in the gut, but also the rest of the body.

The thought is that this modulation not only keeps the body from rejecting the bacteria outright, but also might provide a protective environment favoring that bacteria, including keeping out other competing bacteria. They also suggest some potential connection with auto-immunity as well.

How cool is that?

Of course, all this requires a proper balance of bacterial populations and T-cell modulation – any imbalance can lead to disease. Indeed, they use the term “pathobionts” for bacteria that normally colonize the gut without adverse affects, but still remain pathogenic under certain circumstances.

There has been lots of research in understanding the molecular mechanisms that underly our relationship as host to a whole ecosystem of bacteria in and on our body. This review provides a great overview of what’s known about the potential modulation of the evolution of our immunity. It’s worth a read if you can get the paper.

Image from striatic

links for 2011-01-13

More on bacteria and asthma

image from www.flickr.com There’s a theory going around to explain the rise in asthma: we’re too clean. Research in the past 5 years has slowly been teasing out how this might be.

Link (subscription required): Bacteria and Asthma: Untangling the Links by Jennifer Couzin-Frankel, Science

Scientists have been studying the difference in the incidence of asthma in babies born by cesarian and babies born through vaginal birth, where they are exposed to birth canal bacteria and fungi; or the incidence in children who receive lots of antibiotics or not. Children who are born by C-section or receive lots of antibiotics have a higher incidence of asthma.

Another study is comparing the bacterial flora of children from farms and from non-farm rural settings – farm kids seem to get less asthma.

So far, the link between bacterial diversity and asthma has been an association not proof that bacteria are causing or inhibiting the development of asthma. Yet, it does point to a future where we are less aseptic, less clean in the post-Pasteurian sort of way.

What do you think?

Image from net_efekt

links for 2011-01-12

links for 2011-01-11

The new germ theory

Newgermtheory Lizzie Buchen from Nature (link below) wrote a great article on some cool work folks are doing to change the way we view bacteria.

For example, one group (like a joke, it’s a microbiologist of extremophiles, a neonatologist, and a human microbial geneticist) is studying the effect of bacteria on a devastating intestinal disease in premature babies. They want to know if there’s a role or not for bacteria in this disease.

What’s interesting is that up to now, most understanding of bacteria in humans has been stuff that is pathogenic and can be cultured easily. Bringing in someone who is skilled at finding and characterizing microbes from extremely inhospitable places might help discover new things about our own microbiota.

I don’t know if it’s because I’m all interested now in human microbial ecology or if indeed there has been a resurgence in the study of human microbiology, all I know is that not a week goes by without a new paper or review in this area.

Quite exciting, isn’t it?

Here’s the article: Microbiology: The new germ theory in Nature (no subscription required FTW!).

links for 2011-01-10

links for 2011-01-09

links for 2011-01-07