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Writer's pictureKirk Hartley

Comparing Genomes – Learning How Change Happens – Tort Litigation Possibilities Suggeste

How do genomes change due to environmental forces? A new paper published in the April 5, 2012 issue of Nature sheds some light, and finds an example indicating that change happens the same way even if in different locations at different times. The conclusions are drawn from a team of researchers sequencing and comparing the genomes of various colonies of the pictured fish – a stickleback – that moved from the salty ocean to various fresh water locations. (photo courtesy fo Stanford University). Some specific observations are pasted below from the article summary from ScienceDaily. The bigger picture point is that scientists found the same groups of changes in different colonies.

With that in mind, suppose there is litigation about disease in persons living around a "toxic" location. This study of the stickleback suggests that in due time, it will be possible to compare the genomes of colonies of people living near the site, and control groups who do not live near the site. Plaintiff’s lawyers will argue that causation has been proved if comparative genomics shows that the persons living near the site all have similar changes to DNA or similar epigentic changes to their DNA..

Now go a step further. Suppose there are genomic studies of several groups of people who live by similar "toxic" sites, such as, for example, oil wells in Ecuador. Suppose those persons all show the same changes to DNA which are part of the pathways to cancer, or changes in regulatory microRNA. Suppose those changes are not found in other "colonies" of Ecuadorians. Conclusion?

In this age of sequencing a genome for $1,000 (or less) , new things are possible. That’s why next week I’ll be in London to speak about science and tort law at a forward-looking litigation conference sponsored by Perrin Conferences. Join us if you can – it should be interesting!

Set out below are key quotes on the stickleback research:

"For their latest study, Kingsley, scientists from the Broad Institute of MIT and Harvard, and an international team of collaborators started by sequencing the genome of an Alaskan freshwater stickleback to serve as a standard for comparison. That was an achievement in itself, yielding the first complete stickleback genome sequence.Next, the team followed suit with the genomes of twenty additional sticklebacks from around the world, including ten ocean stickleback varieties found around North America, Europe, and Japan, as well as the genomes of ten freshwater relatives from nearby freshwater locations. They then analyzed the sequences to identify DNA regions that changed whenever the fish made the move from salt water to fresh.

The researchers found 147 "reused" regions in the fish’s genome. That suggests that each time the fish left the sea, variants in this same group of genes helped remodel the fish into forms that were better suited to fresh water, Kingsley says.

So what are these genes? The reused regions include the key armor genes that Kingsley and colleagues previously identified, and many others involved in metabolism, developmental signaling, and behavioral interactions between animals. The study highlights some genes in which alterations likely aid fish adapting to life in a less salty environment. These genes, which are in the WNT family that helps orchestrates embryonic development, adjust the size of small tubes in the kidney that are involved in conserving salt. Freshwater fishes tend to lose salt to their environment, so they need longer tubes to recapture it from the fluid filtered by the kidneys instead of excreting it in their urine.

The stickleback sequences also allowed the researchers to tackle one of the most contentious issues in evolutionary biology. Researchers have battled over what type of genetic changes spur evolution. Some scientists argue for changes to the coding sections of the genome, the portions that cells read to make proteins. More influential, other researchers contend, are alterations to regulatory DNA, which controls the activity of genes. "Here, it isn’t either-or," says Kingsley. The team’s analysis suggests that both kinds of changes occurred during stickleback evolution, but regulatory changes were about four times as common. "We finally get an idea of the relative contributions of both mechanisms, to a whole range of traits that have evolved in the wild," says Kingsley.

Using genome sequences to analyze the sticklebacks’ natural evolutionary experiments "is showing us the genetic mechanism through which animals adapt to different environments," says Kingsley. With this approach, "we can find the key genes that control evolutionary change, helping to bridge the gap between alterations in DNA base pairs and the appearance of new traits in natural populations."

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