Mining museums’ genomic treasures

The golden age of natural history was when Charles Darwin and other scientists focused on collecting stuff. Explorers picked up as many plants and animals as they could, drying them, stuffing them or storing them in small glass jars. They took them to grand museums where the public could see them.

These old collections can seem like relics today. Modern evolutionary biologists study biomolecules with the help of museum collections, which contain billions of samples. Sampling decades- or even centuries-old tissues allows scientists to capture snippets of genetic code from plants and animals and track changes that took place long before biologists even understood what DNA was. Younger specimen give a large sampling to help scientists compare the different characteristics of a species.

Daren Card, a Harvard evolutionary geneticist, has worked with museum samples for his own research on limb development in reptiles. The effects of climate change, as well as evolutionary history, are some of the things museum genomics is delivering, according to Card and colleagues. Knowable spoke with Card about some of the challenges the field faces.

The conversation has been edited for clarity and length.

The human eye can't see much of what scientists want to know about natural history. The interplay between genes and evolution can be seen in the hulking collections of old biological stuff.

Most museum researchers used to focus on naming and understanding the evolutionary history of their species. I'm interested in the ties between the genome and the code that tells an organisms how to build and run itself.

We can study how organisms evolve and adapt to different environments by looking at both genomes and phenotypes, and museum collections give us lots of samples to mine for this work. You can go back and look at old specimen, and you can benefit from the work the museum did to record where the specimen came from, when it was collected, and what observations scientists have made about it over the decades.

Specimens in museums can be better than samples from the field. If you have a creature that is now extinct or very rare, no one will allow you to do any sampling.

The lizards I study are still semi-abundant in natural environments, but having access to museums cuts down on effort. I've used tissue from museums in Australia to sample dozens of species. I would have had to go out and find those species if those weren't there. I might never find what I was looking for even if I got to the right spot.

What is a good example of a scientist using a museum collection to learn something?

We highlighted in the review that one really good one is a study of high-altitude chipmunks in California, and how they have adapted and evolved over the past 100 years or so. These rodents are restricted to the highest mountains in California.

There is concern that the species are at risk from climate change. They are in a tough spot if temperatures continue to rise and they can't move higher up the mountain to cooler ground.

The original work with the chipmunks was started in the early 1900s by researchers at the Museum of Vertebrate Zoology at the University of California, Berkeley, who were led by a gentleman named Joseph Grinnell. The natural history of the West was being documented a lot by him.

When he died in 1939, he was right that museum collections would be used to study biological change over time. One of our co-authors, Craig Moritz, decided to organize a team to reanalyze and sequence some of the high-altitude populations of this chipmunk, and contrast what they found with the samples from the animals collected and catalogued 100 years before. They wanted to see if they could detect genetic changes that would show how climate was affecting organisms.

Nothing changed across most parts of the genome. They found that some genetic changes in the high-altitude locations had become more common over time due to the ecological pressure from climate change.

There are five different versions of the Alox15 gene, which is known to regulate the ability to survive in low-oxygen environments. As the climate changes, perhaps Alox15 is an important gene to track. Scientists should now be able to confirm its function. In the near future, they might track Alox15 variant to inform decisions that will benefit the chipmunks and other high-altitude species. 50 years from now, we will be able to use genetic editing to make threatened organisms more resilient. At this point, that pie is in the sky.

What other discoveries have scientists made?

There are many examples. The other is an analysis of samples from the Museum of Natural History that shows century-long declines in genetic diversity in two butterfly species due to population decline. Between 1879 and 1959 the genetic diversity of honeybees in Bern, Switzerland, was mostly unchanged. This shows that human influence is different in this case.

The Museum of Texas Tech University and the Museum of New Mexico preserved blood samples from deer mice that had been exposed to a hantaviruses that killed 10 people in the Four Corners region of the American Southwest in 1993.

The Swedish Museum of Natural History and other institutions collaborated on a study that identified a previously unknown line of mammoths that were ancestors of the first mammoths to colonize North. Understanding the relationships between different populations of ancient animals is helped by this kind of work.

Good information can be pulled out of something that is old.

It is hit or miss. The best way to preserve is to take a piece of tissue and throw it in a freezer or vat of nitrogen liquid. Time is a factor. The more degraded something is, the longer it sits there.

100 years ago, we didn't know what DNA did or how it did it. The structure and nature of the code were not discovered until the 1950s and 1960s. People like Grinnell were able to preserve things in ways that allowed us to go back to them and try to get usable DNA out of them. Slowly, other biomolecules are coming online as well.

There is a coordinated effort to standardize the way samples are preserved. I think we need to change. We could do a better job of preserving tissues.

What are the other challenges facing the field?

We need to do a better job of recording important attributes. The museums used to preserve a full body specimen, but now they are more interested in the genetics of the person. It can be difficult to tell if a specimen has tissue associated with it when you go to a database. It's useful to have both.

We have been digitizing for at least a decade, but it is not well integrated across collections. Hopefully our paper will make a difference. There is a lot of work to be done.

What have you learned about the lizards you are studying?

We are still figuring out why reptile species lose limbs. It has happened a number of times. Snakes are the most famous examples, but they are not the only examples. The ZRS region has been implicated in driving the loss of limbs within snakes. Preliminary looks I've done, including examining specimen from museums, suggest that this region isn't as important as I'm looking at. The pattern must be driving something else.

Why is it important to understand what part of the genome is involved in evolutionary change?

It is critical for a Biologist. There is a question about what makes a snake a snake. A bird is a bird. Most of the variation we are interested in is driven by genetics. We are at the beginning stages of understanding this. We have done a good job in some model organisms, like humans and mice, but we don't know much about the rest.

Understanding the big question in biology can help us solve big problems, and museums will be a great source of inspiration. Understanding genetic variation and the ways it relates to physiology could have ramifications for health care, or for biologically inspired design and engineering.

This story was published in Knowable Magazine.