Wednesday, January 16, 2008

Hamiltonians are Mutants

A new study published in PNAS (open access) takes a look at the health implications of exposure to particulate air pollution. In this particular study, mice were caged near 2 steel mills and a major highway in the Hamilton, Ontario area and exposed either to ambient air, or the same air passed through a HEPA filter to remove particulate pollution.

When exposed to Hamilton air (but not HEPA filtered air) for 10 weeks (followed by 6-weeks recovery in the lab), the mice had a 1.6-fold increase in sperm mutation frequency and an increase in global methylation of germline DNA. From the article:
"We have demonstrated that exposure of inbred mice to particulate air pollution near two integrated steel mills and a major highway caused tandem repeat DNA mutation and hypermethylation in spermatogonial stem cells. [...] The overall implications of these findings for the health of humans are unclear. Heritable mutation, germ-line DNA damage and epigenetic modifications have the potential to affect disease incidence in the descendents of exposed individuals. In addition to its potential importance in the maintenance of genome stability, appropriate methylation of DNA is critical for imprinting, regulation of gene expression, mammalian development, and disease."

No word yet on whether any of these mutations conferred super-powers.


rob said...

While mice with super-powers would be awesome, perhaps it is asking a bit much.
What the paper doesn't establish is that any of the observed strand breaks and mutations are deleterious. Perhaps these genetic changes are part of a mouse stress response to deal with environmental mutagens. Are the strand breaks ect in random locations??? Basically, I want to see an increase in asthmatic or superpowered mice.

kamel said...

No, they don't show anything about mouse healthiness after exposure to ambient Hamilton air. In fact, they explicitly state in their discussion that the health implications are unclear.

The strand breaks themselves weren't present after recovery (only during exposure), but mutations in the expanded simple tandem repeat locus persisted after recovery, as did the change in global methylation. Obviously their next steps will likely include looking at specific DNA regions for epigenetic differences (instead of global methylation). As you say, it would be cool to find out if there are health effects and, since these changes are germline, how progeny would be affected.

Bayman said...

As to whether mutations arising in DNA sequence would lead to phenotypic variation, I imagine they would do so in the classical way. Most would be deleterious but some might provide selective reproductive advantages.

Here's what I would like to know - Is evolution happening faster in Hamilton? Are novel alleles arising faster within the population?

With respect to epigenetic mutations arising in germ cells, those would presumably be reset in the early zygote and therefore be of no consequence for offspring.

It would have been more interesting if they had looked at offspring of mutants raised in a sterile environment and observed inheritance of the altered methylation patterns.