Science for the Public; WGBH Forum Network; Jurassic Genome

Welcome to the science for the public lecture series science for the public is an organization committed to bringing science information and issues to the general public. This is our Web site fireproofed means the steam's and long. Term. Goals presentation is by Dr. cuius organ. Dr. King is a post-doctoral fellow in the department of organization and evolutionary biology at Harvard University. And an adjunct professor at Brown University. He's an expert in an area called paleo genomes. The reconstruction of ancient extinct genomes. He's been active in developing techniques that make that reconstruction possible. This program Dr. organ explains the kind of information genome can reveal. We're going to talk today a little bit about paleo genomics and about how genomes evolve over long periods of time. And I'd like to start today

by talking about the mammoth genome and mammoths are very close relatives to elephants that are completely extinct now. And yet the entire genome of a mammoth was sequenced earlier this year in 2009. And the researchers did this by using the lumps of hair surprisingly so when they first started the project they crushed a bone and they tried to obtain DNA from ancient DNA from bone and they couldn't obtain very much DNA when they turned to hair and dissolved hair. They obtained vast quantities of DNA and this was a big surprise to the researchers. And what that allowed them to do is to obtain enough DNA where they could sequence the entire genome actually from several different individuals. And this constitutes the the. Kind of the gold standard for paleo genomics.

Here's a picture of a baby mummy mammoth. And these are often exquisitely preserved. Now there are many many species that are extinct and very few as beautiful as this. And so unfortunately these kind of sequencing technologies as great as they are and as interesting as they are can only sequence DNA from organisms about 500 thousand years old and clearly a lot of extinct organisms that we want to know a lot about are much older than that dinosaurs for example which thrived tens to hundreds of millions of years ago. So I'm going to talk today about other other ways that we can figure out parts of the genome and genomic biology and things that are long extinct like dinosaurs. So not only are

we interested in the sequence of the genome we're also interested in things like how big the genome is and this is analogous to wanting to know about body size for an organism. In addition to that we're also interested in how a genome is structured so genome is a string of DNA molecules and they're wrapped up into bundles and organized into things called chromosomes. And here you can see chromosomes from an E-Mu which is a flightless bird related to the ostrich and you can see it has all of these little dots. Are chromosomes called micro chromosomes and these are. An aspect a characteristic of of the bird genome that. We don't have mammals don't have micro chromosomes Yet birds have them and reptiles have them. Most reptiles have them. So understanding how a genome is is organized at the sequence

level how big it is and how it's compartmentalized how it's organized into chromosomes tells us a lot about the biology the genomic biology of species. For example this is a beautiful graph showing the relationships chromosomal relationships between a human and a dog. So the bottom part of this circle is the human genome and it's organized on chromosomes. And the top is on this part is the dog genome. Again organized and its respective chromosomes. So what this map is showing it's a little complex but what this map is showing is that this specific chromosome in the example that it breaks up and parts of it land in different chromosomes in the dog genome. What that tells us is that throughout evolution chromosomes break

apart and reorganize sections of them flip around. And so it's not just that genomes are evolving at the sequence level they're actually on a larger architectural level. They're breaking up and re organizing and shifting all around. And that's important because it brings new genes in association with one another throughout the genome as evolution occurs. So one of the interesting parts of genome biology in terms of genome size. Is. That genome size does not relate to organismal complexity. So a mud puppy and actress has a genome size of about 85 billion base pairs. The human genome is about 3.5 billion base pairs. Yet humans in many ways I'm more complex organisms than my puppies which is. Like a salamander. So for a long time this was a this was a big mystery. It was thought early on that the size of the genome

should correspond to the two organismal complexity because a big genome has a lot of genes in it. Well we now know is that the situation is actually a much more interesting. So this is a cell and the little dots around it are a virus. And this unfortunate bacterium is being infected by a whole slew of viruses and then checking their DNA into the cell. Now what those viruses will do is they'll cause that bacterium to hijack the machinery and cause it to make more viruses and tell oftentimes the cell will simply explode and all of the new viruses will go careening through in the environment. In this case or in our bodies if we're sick. Well we know now that during this process. We can have viral DNA get incorporated into genomes and once it's

there it is just sitting along the string of DNA. Just like one of your genes and these viral genes can copy themselves out and move around the genome. And by doing that they can cause the genome to expand. So it was it was a. Pretty radical discovery with accumulating sequence data for humans in the Human Genome Project. That we realized that a large portion of our genome is composed of these kind of repetitive segments of DNA duplicated copy themselves around the genome. So these lines that's a form of of repetitive DNA signs. That's a form of repetitive DNA and all of these different categories transposons the names don't matter so much. But these are different forms of repetitive viral DNA that copy themselves in our genome. And

by doing so they cause our genome size to inflate. What's interesting if you look at. The amount of our genome that's actually doing something that's making gene products it's this very small sliver. It's about one and a half to two percent of our genome that's actually. Producing products proteins that are building in organisms that are built in our bodies. The rest of it is just kind of along for the ride servicing its own evolutionary course. Now. Despite the importance of these insights and what they tell us about life. We ran into a great problem and that is that about ninety nine point nine percent of all animal species that have ever lived are now extinct. What this means is is that. We have to understand genome genomics understand genome biology. We have a sample size of at best about 1.1

percent. And and that's if we sampled all living animals. So we have a terrible problem. In terms of sample size to understand genome biology and that's caused by extinction in the fossil record. But what we want to do what I'm interested in as a scientist is trying to go back to the fossil record and retrieve some bit of information about genome biology and trying to understand. Broader patterns of genome evolution and genome biology by bringing fossils to bear on an hypotheses about genome evolution. So we're going to go back in time to the Mesozoic era and talk a little bit about about some fossils from dinosaurs and about what they say about the genomes of birds. So first let's have a frame of reference from which we can talk about these subjects.

This is a evolutionary tree. It's called a philosophy by scientists here is living birds. A red tailed hawk and its closest relatives were the carnivorous dinosaurs. This was a group from which birds arose. They're called the theory POTA theropods. If you go down that evolutionary tree then you hit the longneck sauropods and across the other group two of dinosaurs you see the orange whiskey and dinosaurs. And these are things like duckbilled dinosaurs and triceratops and stegosaurus here. If you keep going down the evolutionary tree then you will get to other reptiles and if you go down far enough then you get to other amniotes and then if you go up you get to things like humans and in mammals. So. During the past 10 years there's been a real renaissance in understanding bird biology and how that's been informed by looking at the fossil record and dinosaurs and how we can understand the origin of a lot of bird traits.

So here for example is a bird that's sleeping this is a common pose with a tucked their head behind their underneath their arm and their armpit. And this is a behavior that birds engage in that's thought to be associated with thermal physiology with the retaining body heat while they sleep. We know now that that trait originated in not in birds but in dinosaurs. This was a discovery made in 2004 and it's an animal called my lung which in Chinese means sleeping dragon. And you can see this is a side view here and bottom and you can see its neck is curved around this is its head this is its arm and it had its unsleeping posture with its head tucked behind its arm. So this shows and this is not a bird this is a small carnivorous dinosaur. And that demonstrates that that the sleeping posture that we

associate with birds is actually not a bird trait that it was a dinosaur trade that the birds then just inherited. So birds also have feathers like these beautiful feathers you see here and feathers are remarkable adaptation because birds use their feathers to do everything from flying. See here to insulation to insulate themselves in cold climates. And famously birds also use their feathers to decorate themselves for the purpose of getting maids. So it was a really outstanding discovery. And again in about the last 10 years. Where scientists discovered that. Feathers did not first arise in birds but in fact they started finding them in small carnivorous dinosaurs primarily from China. And this is a this is a recent study of actually body size evolution in carnivorous

dinosaurs. But this shows I think nicely here birds over in this group and this group this this Filani this evolutionary tree nicely shows that there was a. High diversity in body size for these animals some were small Some were rather large but almost all of them had feathers on them. Whether they were birds or not. So whether they were flying or not this means that the only real difference between early birds and some of these small carnivorous dinosaurs was simply because they were flying. But the all the other traits that we think of for early birds at least were shared by these other carnivorous dinosaurs. Another trait that birds have that we're really interested in understanding this biologists is parental care and penguins of course as as are many other birds they're famous for parental care and we want to know how that trait arose.

Well we have paleontologists have found nests and nesting sites they've seen cat scan these eggs and not only confirmed that they were within the eggs were embryonic dinosaurs but you can. But the scientists look at how the bone was developing and it was clear that the animals were developing in such a way that once they hatched they would have been helpless which means that they had to have some form of parental care to survive. Here's In fact a remarkable fossil that that demonstrates parental care even even better. This is an over Raptr and it was discovered actually sitting on its nest these are its eggs underneath it with its arms wrapped around its its nest. So getting back to our main subject of genomics. We know many

traits organismal traits things like feathers light parental care. We know how they arose because we can look at fossils. But what about the genome structure of birds. How did that arise. Well we can we can go back and look at fossils to understand something about genome size as well. Here's a graph. That was first published by a researcher named Hostin who was in 1999. And this shows. The genome size C value is another word for genome size. And this is measured actually in Piqua grams in weight. So what these researchers actually do is they'll they'll actually weigh a genome with very fine measurements with very fine tools. So this is what Hughes did is he broke down birds into four categories of how strongly they flew flightless birds birds fly weakly moderately strong fliers and then really strong fliers

and then looked at the size genome they have now what he found is evident on the scrap that the stronger Flyers have the smaller genomes and that flightless birds in fact have the biggest genomes now out of amniotes that is. Four legged voter Bretz who live on land which is namely mammals birds and reptiles. Birds have that big group. Birds have the smallest genomes. Not only have the smallest genomes but they're. There. There's not much variability in their genome. So they're small and they're uniform they're uniformly small. So this is something that's unique in terms of avian biology bird biology. And we want to know how and why birds have these small genomes. So what we can do is we can leverage a phenomenon called the nuclear tipped

effect and this is simply that the size of a nucleus of a cell. Corresponds tightly to the amount of DNA in the genome. So to refresh your basic biology. The nucleus within a cell is as a. Organ of the cell that contains all of the DNA for for that for that organism. And so the if the genome is bigger the nucleus simply has to be bigger to fit to fit the bigger genome in it that consequently can cause a cell to become bigger. Here's an example of that relationship. You can see these large cells are aquatic salamanders and they have very big genomes. Their genome sizes are about 83 Piqua grams. If you compare those to human red blood cells. They're much bigger. These are human red blood cells

for comparison and human genome size is about 3.5 grams. So there's a strong connection between the size of the genome and the size of the cell and this corresponds nicely across a wide range of animals. So what we can do what I did for some research that I have been engaged in. Is I went and said That's nice that relationship holds for red blood cells. Does that hold for other kinds of cells. So I went through and made thin sections of bone from a variety of different animals. And I looked at the bone tissue and I looked at how big the bone cells were. So on top this is a thin section of bone from a coyote and the colors in it simply represent the direction of fibres within the bone. It's just a way for scientists to to look at kind of the fiber

architecture within a bone. They don't really mean anything for our purposes here. And on the bottom is a sample of bone from area a flightless bird. So we know we can measure the side the average size of bone cells and we can also obtain the average genome size for these species. And then we can make a a we can look and see if they're correlated. If there's a relationship between bone cell size and genome size and just like red blood cells we find that indeed there is a strong relationship. Here you see a relationship between bone size and the bottom and genome size on this y axis where the bigger the bone cell size the bigger the genome size. So what we can do is then we can use that relationship. To. Try and predict how big the genome sizes were of extinct organisms like

dinosaurs. So this is Earth. This is a thin section of a Malwa. Another extinct bird species. And you can see all of these little pockets here are pockets where during life the bones the living bones cells. Reside. So we can measure those and get an estimate for the size of bone cells. Here's another example of a thin section of bone from an extinct species. This is from hotter'n a source Rex This is from a leg bone. And you can see again these little pockets where the bone cells sat during the life of the animal and those structures are preserved within the bone even though the fossilized bone that's over 65 million years old. So when we take those. That when we take those data when we take the size of the bone cell size and the dinosaur and then we take that statistical relationship that correlation we can use those two things to predict how big the genome size

was in dinosaurs. We can then take that information and plot that on a tree and we can color code it. And what you see here on this on this philosophy on the evolutionary tree is a plot of genome size. So over here we have mammals. Here we have birds. Then here's a bunch of extinct dinosaurs. And over here we have reptiles and amphibians. And what you can see is that dinosaur are the living dinosaurs. Birds have. Purple in this case for this map. They have purple sized genomes very small genomes. And our predictions show our method shows that those small genomes existed in these carnivorous dinosaurs. Suggesting that the small unique streamlined genomes of birds did not arise with birds just like these other traits like sleeping like

feathers. That there was a change in the bird genome that it shrunk and that that happened in carnivorous dinosaurs and that that was a trait in birds then later inherited. Now that all the other dinosaurs are extinct. Only trace of that small genome that small dinosaur genome is found in birds. Now as I mentioned earlier the what makes a genome big is the amount of these repetitive elements within the genome. So this is that same pie graph I showed earlier these different kinds of repetitive elements within genomes. Now it turns out that birds have very very few of these. Genomic parasites in their genome. Consequently. Consequently that's what makes their genome small. So on this bar graph this is a bar graph and on the y axis is the percentage of the genome. Composed of.

These repetitive elements. And you can see that these are mammals here. And for comparison living birds have very very small percentage of their genome that's made up from these viral elements. If we move over. And we look at what we estimate for these extinct dinosaurs based on are based on our estimates of genome size that they also had a genome that was very poor in terms of enrichment. It was very poor. For these for these repetitive elements viral elements. And that this other main group of dinosaurs the dinosaurs. Were very rect-Al like they have it looks like they have an amount within their genomes very comparable to lizards and snakes and turtles. We hope you've enjoyed this program and that you will join us for the next program in the series. For more resources. Meanwhile on fossils and

ancient genomes please visit our Web site and check the resources tab. This program will be accessible on Belmont media center TV and other community television stations. And also on the science for the public Web site