Thursday, December 01, 2005

10 questions for Armand M. Leroi   posted by Razib @ 12/01/2005 09:43:00 AM

Below are 10 questions I posed to Dr. Armand Leroi, the author of Mutants. My questions are in bold.

1) Your biography suggests that you are a "citizen of the world." Do you feel a special attachment to any of the nations that you have called home?

Like many people who have grown up in different countries, I have been left with a sort of restlessness, a desire to periodically sever ties and move. But I must admit that having now lived in England for nearly ten years, I have come to love this country and its people very much. In another ten I may even begin to understand them.

2) Your primary research focuses on the development of C. elegans. Seeing as how this is a selfing nematode, do you think that it is truly a very good organismal model for the "evolutionary" part of evo-devo in the general sense?

The beauty of C. elegans lies in its simplicity, regularity of structure and transparency. I do not mean "transparency" in any metaphorical sense, but in the literal one: you can see every cell in its tiny body. Importantly, the properties that make C. elegans so wonderful to work with are shared by many other species of nematode. So you can do comparative biology -- evo-devo -- on a cell-by-cell basis: something that is unique to worms and very powerful. For proof of this I recommend Ralf Sommer's work on the evolution of the vulva.

C. elegans' strange habit of selfing doesn't affect such comparative studies. It does, however, affect the population genetic structure of the species: it means that the species is largely composed of many clones. For this reason it's not terribly useful for microevolutionary studies. If you want to do a selection experiment, Drosophila remains a far better choice.

3) How did you come to John Brockman's attention? I assume you didn't send him a telegram with a letter of introduction from Richard Dawkins attached?

I knew that Brockman was the ultimate science-writer's agent. So I faxed him a five-page proposal cold. He, or rather Katinka Matson, his wife and President of Brockman Inc., picked it up off the floor; she has been my agent ever since. She tells me that it was the title that caught her eye: "Mutants". There's a lesson there for the aspirant writer.

4) You've shot to public intellectual status in large part based on your recent op-eds in relation to race. Have you read the rebuttal site to your essay A Family Tree in Every Gene, If so, how would you respond in a pithy fashion to their criticisms?

I have read the essays, and have considered responding to them. But where to start? When last I looked, the SSRC website contained a dozen papers written by some 20 academics united by little more than a collective, if heartfelt, sense of outrage.

But were I to respond I would ask my critics to do two things. First, when considering scientific results to set questions of history, ideology and social justice aside. And, second, to learn some genetics. Of course, given that my critics are overwhelmingly social scientists and historians, I hold no hope that these modest requests will be fulfilled.

5) You've offered that hybrid individuals with the parents being of relatively distinct racial origin might be more beautiful than unadmixed individuals on expectation. This appeals to an intuitive notion that I often encounter in my day to day life, though people seem to imply that the 'hybrid vigor' derives from heterosis or overdominance, while you suggest that it is due to the masking of deleterious recessive alleles (i.e., dampening of inbreeding effects). Do you believe that it is as simple as all that in that there is a relatively inverse linear relation between inbreeding coefficient and fitness? (at least across the genetic distances you are implying) What about the possibility of countervailing genetic incompatibilities acting as a break on the beneficial effects of the masking of negative recessives?

[this response is temporally out of synch with the others because there were some emails exchanged about it]

The idea that human beauty might depend on mutational load was a speculative one, and presented as such. But it is consistent with a great deal of theory and experiment in animals where it comes under the general rubric of the "good genes" hypothesis for sexual selection. Can concealment of deleterious recessives account for the common notion that mixed-race individuals are beautiful? Perhaps. But there are other explanations. One might be that mixed race individuals present us with novel, unexpected, combinations of features -- novelty itself is beautiful. In the future we should be able to test whether beauty does indeed depend on mutational load by estimating the latter directly from genome sequences.

Might racial mixing ever be deleterious? The conventional answer is "no"; it is certainly the one that I thought to give. Razib, however -- ever alert -- directs my attention to recent report in Nature Genetics that suggests a possible case of hybrid breakdown in humans.

Helgadottir et al. (2005) identify a haplotype that confers high risk for myocardial infarction in African- but not European-Americans. The haplotype is rare in Africa and so African-Americans who have it probably get it from European ancestors. But what accounts for its evil effects in African Americans? One explanation is that Europeans are protected by some other genetic variant that Africans also lack -- as do most African Americans.

Of course hybrid breakdown is not the only possible explanation for this result. It could be that African Americans are exposed to some environmental factor that European Americans aren't, and it is this that interacts with the haplotype to cause myocardial infarctions. Without knowing more about these other factors -- genetic or enviromental -- we are left with no more than a provocative observation. Nevertheless this study highlights how little we know about the consequences of genetic structure in human populations.

6) Who selected the photos for MUTANTS? Some of the pictures attracted quite a bit of attention in public places when I was reading your book.

I did. When searching for illustrations, I invariably sought old platinum prints or even older lithographs. I did so because such images are beautiful things in themselves. True, they are macabre. But they are less dehumanizing, and no less accurate, than the harshly coloured photographs that can be found in any modern clinical genetics textbook.

7) You've done research in the United States and England, what are the differences in the scientific cultures and variations in terms of how one has to get funding?

Funding is easier to get here, and there's less bureaucracy than in the US - but you get less money too. But then, we Brits (if you will permit me the identity) take pride in doing more with less: on being nimbler, smarter, than our American colleagues with their vast resources. There's some truth to that, but probably less than we like to think. And when we visit US labs we return awed. The single greatest impediment to British science is its unfriendliness to non-EU graduate students. US labs are filled with brilliant students from all over the world, notably China. We're lucky if we can get a single Belgian.

8) If you had to do it over again would you modify your educational track? If so, how?

I would listen to my father when he said I should learn German. But I was 14...

9) In evolutionary genetics the infinite allele Wright-Fisher models have been ascendent since the Modern Neo-Darwinian Synthesis (along with modifications introduced by Kimura, Crow, Ohta, etc.), but Evo-Devo is bringing a new macroevolutionary perspective to the debate. At the end of MUTANTS you acknowledge that you focused on genetic mutations of large effect rather than continuous traits due to additive polygenic variance, and that the latter is a very fascinating topic in and of itself. How would you express succinctly the relative importance of these processes across the taxa of the tree of life? For example, would you accept a dichotomy between intraspecies relevance of microevolutionary models based on the Wright-Fisher framework, while macroevolutionary events like speciation are sequestered under the umbrella of Evo-Devo?

There are good reasons - the reasons that Fisher gave - that evolution proceeds, in general, by the substitution of mutations with rather weak effects. That is, mutations of large effect will tend to be deleterious. (If you don't think so, then opening "Mutants" at almost any page should convince you otherwise!) Given that, I tend to be conservative on this question: the onus is clearly on the macromutationists to make their case by directly demonstrating the role of major mutations in evolution. It's not enough to simply demonstrate that you can make a four-winged fly in the lab or show that Hox genes are important to the development of lots of animals.

Of course, it's very hard to identify the number and kinds of genes involved in adaptation and speciation. But there are an increasing number of studies that bear on the question. Such studies are based on those rare cases where we can cross two closely related species in the lab and get viable, if not fertile, offspring. They tend to show that adaptations are formed by the fixation of alleles with a range of sizes: a few biggish ones, and then a lot of smaller ones. For a deeper discussion of these questions interested readers might read Leroi, A.M. 2000. "The scale independence of evolution." Evolution and Development 2: 67-77. It's not very technical and still fairly current.

10) If in 10 years you could purchase your own full genome sequence for a month of your salary, would you do it? (assume privacy concerns are obviated)