Monday, July 18, 2005

The Genotype and the Phenotype and How to Measure Divergence

PZ Myers has ventured out from Minnesota to visit Toronto. His car died on the way back to Morris, and he decided to do some reading, which led to some blogging on, what else, evo-devo, which, in turn, led to a discussion of Endless Forms Most Beautiful, and Jerry Coyne's review of the book. Coyne was somewhat critical of the book, and I'm a bit more apologetic of Coyne (being a population geneticist) than is Myers (being a developmental biologist). Myers writes:
"Carroll begins by noting the disparity between the rates of evolution in proteins vs. the rates of anatomical change. Compare chimpanzees and humans, for instance, and you see major differences in morphology, but the differences at the level of the gene sequences are relatively small."
My biggest problem with comparing sequence level divergence with anatomical/morphological/phenotypic change results in how well we understand the two processes and how we measure the two types of divergence (genotypic vs. phenotypic).

For those unfamiliar, sequence level divergence is much easier to calculate and is extremely more objective than phenotypic divergence. Of course, choosing the sequences to study is somewhat subjective, but with whole genome sequences we can examine the entire genome at whatever scale is appropriate (DNA level for closely related taxa, and protein level for more distantly related taxa); this removes some of the subjectivity.

Morphological divergence, on the other hand, is more difficult to get your head around. How do we choose characters to study? How do we measure those characters? What role do our predispositions and preconceptions play in these analyses? Molecular data is not immune from these limitations in any way, but they pose a much bigger problem for anatomical characters (in my opinion).

Who is to say that the "major differences in morphology" between humans and chimps can't be explained by the protein divergence between the two species? Well, me, for one. I do believe that expression divergence (in both cis and trans), as well as splicoforms, is important for morphological/phenotypic diversification. I'm not sure, however, what proportion of morphological divergence is due to changes in cis elements and what proportion is because of evolution of protein sequence. Oh, and don't forget the role gene duplication can play in allowing genes to evolve novel expression profiles.

We have a hard enough time trying to figure out how to measure expression divergence, and this seems to be the next step up in complexity from the sequence level. I'd shy away from comparing sequence level divergence to morphological divergence until we have better statistics for estimating phenotypic divergence (at any level, from mRNA expression to anatomy). Some neat work on the evolution of gene expression, by the way, is being done by one of Sean Carroll's former students, Tricia Wittkopp. Wittkopp is working to unravel the relative roles cis elements (i.e., regulatory sequences) and trans elements (transcription factors and their cis and trans elements) play in the divergence of gene expression. Plus, she gets mad props for doing a post-doc with Andy Clark, a top-notch population geneticists, showing you can straddle the line between developmental biology and population genetics.

Basically, comparing sequence divergence to anatomical divergence is -- to overuse the metaphor -- like comparing apples to oranges. Before anyone starts saying the amount of morphological divergence cannot be explained by the amount of protein sequence divergence, wait until we have more objective measures of morphological divergence.


At 7:43 AM, Anonymous John A. Davison said...

We are prasctically identical at the DNA level with our living closest relatives, the chimp, gorilla and orang. The distinguishing features are evident as the presence of rearranged discrete blocks of genetic information in the form of inversions, translocations, fusions etc.

There is not a shred of evidence that any of these changes required an alteration in the genome in the form of allelic mutation. They apparently arose spontaneously from within the evolving genomes themselves. There is absolutely nothing in the Darwinian model that can be implemented in support of such evolutionary changes. Just as ontogeny proceeds now as an internally driven, front-loaded, auto-regulated and auto-terminated series of irreversible cytogenetic events, so apparently did phylogeny, a phenomenon of the past, do the same. That is the essense of the Prescribed Evolutuonary Hypothesis. In any event, chance has played no demonstrable role in phylogeny just as it now plays no such role in ontogeny.

In short, neo-Darwinism continues to demonstrate that it had nothing to do with creative evolution beyond its limited capacity to produce varieties in some but not all forms. It remains the most thorougly tested and perfectly failed hypothesis in the history of biological science.

It persists only for ideological reasons. Any alternative is simply unacceptable to the materialist atheist mentality which defines the core of the Darwinian paradigm.

It is long past time for a new hypothesis and I have, with the aid of some of the most penetrating minds of two centuries, recently offered one.

Referring to ontogeny and phylogeny:

"Neither in the one nor in the other is there room for chance."
Leo Berg, Nomogenesis, page 134

At 1:19 PM, Anonymous Anonymous said...

Aaron Haspel had a good post on this a long while ago. He summarizes it succinctly as "The Mapping Fallacy":

-- Matt McIntosh

At 4:55 PM, Blogger RPM said...

Haspel says we don't know how the genotype relates to the phenotype (or, as he puts it, how the input relates to the output). I'm saying we haven't defined the phenotype (the output) well enough yet to even begin thinking about relating the two.

At 2:12 PM, Anonymous ThomH said...

RPM, following you as best I can, it seems we have a difference of scale here?

On the level of DNA, we can map out with broad agreement and hard evidence the divergences.

But we still haven't specificed with enough detail the development mechanisms.

Furthermore, the definition of a phenotype is much slipperly-- much more what we agree to recognise as differences.

So whereas it's fine to speculate on how divergence on the DNA level contributes to divergence on the morphological level, we should go easy right now in assigning direct cause-effect correlations.

Is that a simplistic, crude but mostly correct summary?

At 4:24 PM, Blogger RPM said...

Basically, DNA (or protein sequence) divergence is easy to measure because it's one dimensional and constant throughout and organism's life. All you have to do is count up the number of nucleotides (letters, eg A, C, T, G) that differ between two related sequences and you have a measure of divergence. Granted, there are more complex ways to measure divergence than a simple p-value, but they all come down to the differences between one dimensional arrays.

With any measure of divergence based on phenotypic differences (gene expression differences, morphological difference) we begin dealing with much more complex data sets in which the environment, life stage, and subjectivity begin playing more of a role. I don't think we're at a point yet were we can accurately compare sequence level divergence with phenotypic divergence because of the current limitations in measuring phenotypic divergence.

At 10:41 AM, Anonymous John A. Davison said...

I maintain as did Otto Schindewolf that the environment never played a role in creative evolution beyond acting as a stimilus for the release of an innate potential. So much for mutation, natural selection and Darwinism generally. Natural selection, which depends on mutation, now as in the past was a purely anti-evolutionary, entirely conservative mechanism which never had anything to do with the formation of species or any of the higher categories. Get used to it. Leo Berg did. Reginald C. Punnett did. Henry Fairfield Osborn did. Pierre Grasse did and, as I just indicated, so did Otto Schindewolf. Join with the forces of rationality and get with the program folks. Darwinism in all its guises is a joke which has metamorphosed first into a scandal and now finally into a hoax. It is nothing but the only conceivable refuge for the congenital and apparently "prescribed" atheist
mentality that defines the Darwinian paradigm. Soren Lovtrup called it a deceit. I call it the biggest farce in the history of Western Civilization.

There now, I feel somewhat better.

At 7:29 AM, Anonymous John A. Davison said...

I love this silence. It is living proof that we critics of the Darwinian fairy tale still are not allowed to exist by the iron fisted establishment. I am delighted to join Bateson, Goldschmidt, Schindewolf, Grasse, Boom and Berg as an even more outspoken critic of the biggest hoax in the history of science. If they had not been such perfect gentlemen, Darwinism would have succumbed a lot sooner. It is great sport being in on the kill. It will soon join Phlogiston and the Ether and also become little more than a footnote in the history of science.

The S of Selection can now join the P of Phlogiston and the E of the Ether to spell ESP, shorthand for extrasensory perception don't you know.

Ask not for whom the bell tolls. It tolls for neoDarwinism.

At 9:16 PM, Anonymous John A. Davison said...

I see you have denied me comments at your "I'm busy doing science" thread. Every time things like this happen it means only one thing. It means that i have won and my adversary has lost. Write that down. I recommend lifetime banishment. It is the only effective way to muzzle me in the face of such shabby tactics.

"War, God help me, I love it so."
General George S. Patton

At 2:04 AM, Blogger RPM said...

I shut down comments because you were commenting on your own comments (i.e., talking to yourself in the comments section of my post). You kept posting comments and no one was wasting their time replying to you.

I'm going to shut down comments on this post as well, seeing as you're the only one posting comments (3 in a row without any response).

If you'd like to post your own opinions, I'd suggesting getting your own website to it. I won't sponser the John Davison talks to himself hour on evolgen.


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