Recovery February 2, 2001 (delayed from an earlier publication)
 Returning from a meeting is always so much fun. First I have to remember exactly where my office is. Well, not really but I usually focus so much on the meetings that other stuff gets pushed out of my long-term storage. Like passwords, etc. My brain works in such a quirky way. I will forget some of the most important items in just a few weeks, while remembering just how many hours of the day a koala sleeps.* As a freshman in high school, I forgot the combination to my locker over Christmas break once. Yet, I still know the number of our telephone when we lived in Corpus Christi, Texas (we left when I was 8 years old).** Strange.

Part of the problem recovering is just getting back on Seattle time. Flying on a plane for multiple hours is really debilitating. The plane left Hawaii after 2 PM Hawaiian time on Monday (4 PM Seattle) and got in at 11:30 PM. It took way too long to get our luggage, so it was early Tuesday morning before I got home. (I will refuse to ever fly on Airbus' new double decker super-jumbo jet. I can just not imagine what it would be like to board, deplane and wait for luggage when there are 800 other people trying to do it at the same time. It takes an hour or so to get out of the airport when there are only half as many people. If you feel like cattle now, how will the Airbus plane feel?)

The other problem I had was illness. The last few days of the meeting, my sinuses were really having a great time. The first inkling I had was a sore molar in the middle of the night. I used to worry about this until my dentist explained that there are lots of spaces in the skull connecting sinuses and some run just above your teeth. I can always tell when it is sinus blockage that is causing the problem because the molar only really hurts when I shake my head. Weird. By the morning, the stuffiness had moved throughout my head and I was blowing my nose a lot. Which I did for the next few days.

So, naturally, I was not in very great shape at Immunex on Tuesday. Coffee just did not work. I was finally able to get Lotus Notes working (a burnt offering helped) and I was able to navigate the new phone system.

The Big Island was fascinating. The west side that we were on gets very little rain. It is covered in various lava flows from Mauna Loa and Mauna Kea. Very dry and very rocky, and from outer space it looks like something. In fact, this site discusses the similarities between these lava fields and other worlds. No wonder it makes such a stunning location for the Ironman Triathlon.

Islands provide a unique view of the interactions between life and the environment. That is why the Galapagos were so important to Darwin. The dry side of the Big island was not always so desolate. Sure, volcanic eruptions did some damage but humans had the greatest effect. Back in the 18th century, this part of the island was covered with trees and was a temperate rain forest. Then a merchant happened to tell King Kamehameha that these trees, the sandalwood, could bring a lot of money in Asia. As with many rulers, Kamehameha needed cash, tons of it. So, using native labor, he cut down almost all the trees. By 1821, they were harvesting almost 3 million pounds a year. There are very few native sandalwood trees around today.

Captain George Vancouver (yes, THAT Vancouver) left some cattle with King Kamehameha in 1793. The king was so taken with animals of such large size that he made it taboo to kill them. A population of 5 tame animals in 1793 had grown to over 40,000 wild ones by 1840. The largest private ranch in the United States, The Parker Ranch, was started by the first man allowed to shoot the wild cattle of Hawaii. He married a local princess and eventually brought over 225,000 acres under his control. The cattle, along with introduced pigs and goats that became feral, proceeded to alter the remaining forests of this area, preventing sprouts of sandalwood trees from gaining a foothold.

Now, this area is not all desert. There is quite a bit of plant life here. Particularly a type of grass called fountain grass. You can see tons of it in this picture from the Ironman competition. I found out that this is not a native plant. It was a domesticated, ornamental plant. It was introduced from a single plant brought to the island 50-70 years ago. It escaped and started spreading rapidly. Supervised burns were done in order to try and control it. However, no one did their homework. This particular breed of grass is pyrogenic. It requires fire in its life cycle in order to crack the seeds. Needless to say, it spread like ... wildfire. It seems that, before man arrived, wildfires were previously unknown on Hawaii. The normal fire cycle did not include many lightning strikes that could start fires, so the native grasses never developed resistance to fires. The fires not only destroyed native grasses, they created environmental niches allowing introduced grasses to take over. It now covers the leeward side of the island, forcing out many other species.

Now, this is not a polemic about how bad humans are when they introduce new species to an island. Every species on an island is introduced at some point. But it made me think. How could a single plant do so well? How did the cattle increase 8000-fold in 40 years? I mean, wouldn't the species be so inbred that it would not survive well? How can it out-compete species that developed there? There should not be enough diversity in a single plant or animal to provide for a successful species. Natural selection works with species diversity to mold evolution. No diversity should result in poor survival over time.

Inbreeding usually brings negative, recessive genes to the front. With no diversity to buffer these "bad" genes, it should make it harder for a species to survive. I suppose you could have a species expand from a group that had only "good" genes but how likely is that? Yet, there continue to be examples on the islands of this sort of thing. There was an article in a Hawaiian newspaper about a huge flock of parrots on Maui that are rapidly expanding. They are all derived from a single pair of parrots released just a few years ago.

There are many examples of how inbreeding can be deleterious. Cheetahs are so inbreed that skin can be transplanted between individuals without being rejected. They have survived this bottleneck for 50,000 years. But their fertility is reduced and, unless they overcome this lack of diversity, they have little hope for survival. Just how many animals are required to survive a bottleneck in order to provide enough diversity? Why can some animals expand their population tremendously even when they start from the minimal number of 2?

A communication in Nature this week only adds to the puzzle. For over 300 years, a feral herd of cattle has roamed in the north of England. Darwin even studied these Chillingham cattle. There are extensive records of births and of deaths. The lineages of all extant animals are known. There has been no immigration of other cattle. Yet, there has been no loss of fertility or viability.

This paper looked at 25 microsatellite markers, covering 15 out of the 29 autosomes. They amplified DNA samples from 13 animals. For 24 of the 25 markers, the cattle were homozygous. For the last marker, 9 were heterozygous for 2 alleles, and two were homozygous, one for each allele (the other 2 samples did not amplify). Statistically, about 96.5 % of the alleles should be homozygous after the 67 generations of Chillingham cattle. No too far from the observed number.

The bovine genome is 30 morgans long, so 30 crossover events would be expected every meiosis. Starting with initial complete heterozygosity, random breeding amongst individuals for 67 generations would be predicted to result in virtually complete homozygosity , with only 30 heterozygotic regions, each with an average length of 1.5 centimorgans. So these cattle are almost as inbred as some strains of lab rodents, yet they have been able to survive for over 300 years, with little apparent loss of fecundity. They appear as hardy as any breed, and, without the extensive documentation of their habitat, one would be surprised to find out that they were not just like any other herd.

This idea of a vigorous population growing from just a few progenitors has to be a very important aspect of life on earth. There are a lot of examples of reduced diversity in a species appearing to have little effect on its viability. In fact, humans are a great example. We appear to have gone through some sort of bottleneck many thousands of years ago (This theory is still somewhat controversial. I may discuss some of the recent evidence in a subsequent column.) Yet, our species appears to have gone the route of increasing diversity over time, not less.

Mitochondria DNA mutates at a faster rate than chromosomes so they are very useful for examining lineages over the last 100,000 years or so. And, since they are inherited mainly through the mother, the lineages can be more simply generated. Examination of the mitochondrial is what was used to first postulate the African Eve and the Out of Africa origin of humans.

This theory states that Homo sapiens arose in a small region in Africa and spread throughout the world, forcing to extinction other forms of Homo, such as Neandertal and Homo erectus. There was no gene flow between the groups. We just forced them out, like the introduced animals on Hawaii are forcing out the native species. The data from living humans seems to imply such a possibility, since the mitochondrial genes with the greatest diversity were found in Africa, indicating that their DNA had been around the longest.

But an alternate theory exists, based mainly on physical evidence rather than genetic. In this Theory of Regional Continuity, there has always been only one species of Homo that left Africa 1.5 million years ago. All the regional populations interbred, allowing constant gene flow to occur throughout the world. In this model, Homo erectus was not replaced, it was assimilated.

Now, one of the aspects of the mitochondrial data that, while self evident, is critically important - all this data comes from living humans. You examine the DNA sequence from people around the world and find that the further away from Africa you go, the lower the mitochondrial DNA diversity. This would suggest that the oldest humans came from Africa. But this sort of analysis can be misleading, since low-recombining regions of DNA, such as mitochondrial DNA, may be under very strong selection pressures. A strongly selected for sequence of DNA could "sweep" through a population very rapidly is there is generous gene flow.

So, how about looking at the mitochondrial DNA of older humans. Those that are no longer living. Now I do not mean looking at your grandfather's DNA. There are groups that are isolating mitochondrial DNA from fossils, such as Homo sapiens or Neandertal. There are several techniques for doing this and it sometimes works quite well. Looking at Neandertal samples, one group showed that they belonged to a lineage that diverged before the most recent common ancestor for all living humans. Their DNA was not found in the genome of any living human. This has been used as evidence that the Neandertals did not contribute any genes to extant humans and were in fact a separate species.

But this may not be true and a recent paper in PNAS complicates the issue. They examined mitochondrial DNA from 10 fossils from Australia. These range from 2000 to 60,000 years old but are all individuals that appear to be modern Homo sapiens by morphology. There are definite difference between erectus and sapiens bones. Four were from gracile members while the rest were from robust individuals, whose morphology is outside the range of living indigenous Australians. The first thing they found was that, even though there is a great difference between the bones of gracile and robust individuals, there was little difference in their mitochondrial sequences. Just as we have differences between the shapes of gymnasts and football players, even though we are the same species, these ancient individuals also showed great differences in morphology.

In fact, the oldest sample, over 60,000 years old, appears to be a modern human by morphology. Yet, its mitochondrial DNA is so divergent from ours that it falls on a node outside the lineage of all living humans. Just like the Neandertal DNA. The mitochondrial sequence has not been found at all in any living human being. It represents a branch of our family tree that has not left modern day survivors.

This does not mean that all humans evolved in Australia. It simply means that an individual that we would all agree looks like a modern human existed in Australia 60,000 years ago. It does complicate things though. Lineages from extant humans appear to originate about 100,000 years ago. Yet 40,000 years later there is a morphologically modern human with mitochondrial DNA that is outside this lineage.

The notion that humans came out of Africa simply because the oldest mitochondrial genomes are found there is just too simplistic. The DNA from Australia is "older" by the measure of diversity, yet we are not saying humans originated in Australia. It is one thing to talk about replacement of an entirely different species, such as Homo erectus, by humans. It is trickier to say that a group of humans, from which we descended, replaced another group of humans on Australia. Perhaps, one species did simply remove another. But, selective pressure could have also removed one lineage in a "selective" sweep. Interbreeding would have done this. There never were two separate species. There is no way to separate these two possibilities.

What is apparent is that there have been substantial changes in the lineage of humans. Whether this was due to replacement of individuals or simply replacement of certain genes by selective pressure can not be determined. Did founding members of our modern lineage take over the environment, pushing out our genetic neighbors, much like the parrots on Hawaii are destroying native bird populations, or did they simply interbreed, providing a flow of new and useful genes that the environment selected for? Replacement or selection?

Recovering DNA from bones that are over 50,000 years old is simply amazing. Being able to actually learn something from these old bones is tremendously exciting. What else can we learn from the bones of our ancestors? I'm holding out for something that cures jet lag.

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*22 hours

**UL3-8207