I’ve been trying to put together my reader for a new unit (class) on human evolution at Macquarie University that I’ll be doing next semester. As usual, I’m doing this at the 11th hour, but this should be my last completely new, never-before-taught-at-my-university class for at least a year (I hope). In the process of checking out the most recent edition of my favorite human evolution journals, I happened across an odd and really thoughtful piece by Prof. Kenneth Weiss, who’s at Penn State. In the past, I’ve remarked about ‘post-neo-Darwinism,’ a term that I’m sure causes grimaces and eye-rolling, but that I think is worth discussing (I can’t take credit for the term; I think I heard it from Prof. Emily Schultz of St. Cloud State University at the last meeting of the American Anthropology Association).

By the way, Daniel posted a great ‘Evolution Round Up’ just recently with a whole lot of interesting material (I especially enjoyed Mo’s piece at Neurophilosophy on ‘Synapse proteomics & brain evolution’). We’re not really an evolution theme website, but it’s obvious how important it is to locate brain development in frameworks consistent with evolution. (I’ll come back to why being overly persuaded by evolutionary frameworks can be pernicious in a second, and it’s broader than my recent rant about memetics.)

Unfortunately, because the Weiss piece is more of an essay, in his recurring column entitled ‘Crotchets & Quiddities,’ there’s really no abstract of it, so I can’t link through to a nice concise summary of the piece. So, more than usual, I’m going to copy blocks of text from his essay, ‘All Roads Lead to… Everywhere?: Is the genetic basis of interesting traits so complex that it loses much of its traditional evolutionary meaning?’, before I get into my own commentary. Obviously, if you have access through a good research library, you should be able to get your hands on the original article. (More on Weiss’s columns can be found here — they’re quite good.)

The set-up for Weiss’s discussion is the idea that it doesn’t make sense to talk about ‘THE road’ to any particular place in a complex systems of highways and secondary roads because there are many routes:

With such choices, it doesn’t make much sense to ask, ‘‘What is the road to Rome?’’ In a somewhat similar way, rapidly growing knowledge about the nature of genomes and what they do suggests that what’s good for the Romans is good for biology as well. Instead of a gene for this and a gene for that, we face the possibility that all genes lead to everywhere, which may have important
implications with regard to our understanding of the genetic basis or evolution of traits like the shape of the skull, a skull, or this skull. If all real roads lead to the Circus Maximus, do all our craniofacial genetic roads lead to the foramen magnum?

Weiss’s is a subtle argument, so I’ll probably get in trouble both from those who don’t think I’m doing it justice to those who will radically misread what I’ve written and think I’m some sort of Creationist or anti-Darwinist. But Weiss points out that, even though we didn’t understand the mechanisms through which DNA affected the development of traits, for a long time, the neo-Darwinist consensus was that genes coded for traits. Therefore, even though we didn’t necessarily know the mechanism, evolutionary theorists were pretty confident that they got the general picture: ‘We didn’t have to know what specific genes were responsible for a shorter face, a wider pelvic outlet, or thinner tooth enamel to assert with confidence that hominids evolved by selection favoring those genes.’ This story — variation in genes leading natural selection to act through phenotypic expression on underlying genes — is sort of the ‘Neo-Darwinist’ ur-narrative. Darwinist natural selection theory combined with early, pre-genome sequenced genetics.

Weiss than reviews recent discoveries, such as the role of non-protein coding introns in DNA and RNA (but spliced out in mature mRNA); the role of what was thought to be ‘junk DNA’ in regulatory proteins, including the fact that they seemed to get copied multiple times in some cases and radically influence how protein coding genes behaved; that coding regions can be respliced to produce different sorts of proteins, even in the same cell; the importance of histones in the timed wrapping and unwrapping of DNA; that other cells can interrupt or facilitate coding from different parts of a DNA strand; that some mutations in cells can persist and reproduce in a body even if they are not transmitted to the next generation; that there are protein-protein interactions that affect expression of genes; and even that members of the same species don’t always have the same number of genes. (Weiss details even more in a whirlwind discussion of recent developments.)

For a great example of this, see Ed Yong’s recent post, RNA gene separates human brains from chimpanzees, on the blog, Not Exactly Rocket Science. His piece discusses the rapid change in the HAR1F gene, a gene that codes for a bit of RNA with an odd structure but unclear function, although there is some suggestion that the RNA is involved in embryonic brain development.

The basic idea that a gene produced a trait turned out to be simplistic in many cases. As Weiss explains:

Then we learned that most genes seem not to directly affect a final function, but instead work through signaling cascades in which networks of proteins interact in hierarchically ordered stages. For a function to be fulfilled, all of these genes must be expressed in the relevant spatial and temporal contexts.

In addition, and perhaps most importantly for our discussion, many genes were discovered to be pleiotropic, appearing to code for different proteins serving a variety of functions in different parts of the body throughout the lifespan of the organism. That is, a gene was not for ‘A trait’ but contributed to a number of different traits, even as it was embedded in much more complex intra-cellular processes that affected its expression.

The experiments in animals showed that there were alternative ways for organisms to develop, even when genes were removed:

In single-celled species, many or even most genes can be experimentally deleted with little effect on the cell. This seems to be less true in complex organisms like mammals, but the jury is still out because, for example, genes can be experimentally knocked out in mice with effects that depend on the strain of mouse that’s used, showing the availability of alternate roads to Rome.

As he summarizes:

The point of this breathless race through recent genetic history is to provide at least a sense of the way that many new findings add to, but never reduce, the degree of potential genetic complexity to biological traits; that is, the complexity of the relationships between phenotypes and their underlying genotypic basis.

The attempt to define ‘a gene’ has thus grown far more difficult, and the language of geneticists has moved, from discussion the ‘gene for‘ a particular trait to talking about ‘genetic effects on‘ particular traits. It’s hard to know, as Weiss discusses, what to make of this systemic variation in the way that genetic material gets expressed; he says it’s hard to know if the complexity should ‘put us to sleep from boredom or should awaken us to different ways of thinking about the traits we care about’ (I’d tend to favor the latter).

To explain the significance of these findings in genetics, Weiss discusses the many evolutionary changes in hominid skulls, changes that are absolutely crucial to understanding the emergence of a distinctly human morphology and neurology, including everything from cranium size and shape to the positioning of the spinal cord, bipedalism, jaw development, sensory abilities, and a host of other human traits. For a long time, we couldn’t really discuss how genes produced these different traits, but had to assume that, somehow, natural selection was acting upon genetic variations in those genes producing things like reduced mandible robustness or a foramen magnum that moved beneath the skull. Whereas human evolutionary theorists once talked about how natural selection acted on ‘face shape genes’ to shrink a primate snout or to increase the forehead, we now better understand how genetic material effects craniofacial form.

Rather than ‘a gene for face shape,’ we have learned a lot (a lot I don’t understand) about ‘many different signaling and developmental networks, each containing many genes’ that interact during development. Traits tend to emerge from networks or systems of interacting genes, with certain genes providing important bases or limits (and subject to patterned failure if they don’t function correctly).

In the case of face and head shape, Weiss describes how different attempts to ‘gene map’ (to correlate variation in gene types with phenotypic differences within a species) tend to produce a whole range of genes that contribute to any trait, and often genes that do not show up in situations where serious anomaly produces a severe defect. He summarizes these studies and relates this back to the many genetic mechanisms that have been recently discovered:

What this appears to mean is that the bulk of genetic effects on craniofacial variation is exerted by many genes making contributions to the trait that are important in the aggregate but too small to detect individually. Presumably, these include the kinds of newly identified genetic elements listed earlier. All of this would be consistent with the idea that evolution molds traits only very gradually, with the large array of newly found mechanisms available for use in the process.

The basic genetic framework for organic structure turns out to be very conservative, very ancient, and (by implication) very versatile, as it produces a wide range of different species:

A final fact that is clear from experimental, observational, DNA sequence, and functional data is that developmental networks are highly conserved phylogenetically. The networks’ main genes that we see today are ancient. All the genes vary. Some do come and go, but there is substantial conservation in the basic developmental genetic structure. A frog, a chick, and you all used very homologous networks and control systems to progress from egg to adult.

In other words, the differences between species may be much more about regulating how genes work rather than introducing entirely new ones; this may help explain the extraordinary genetic similarity between species (something Jonathan Marks discusses in, What Does It Mean to Be 98% Chimpanzee?)

The large number of gene sites contributing to any trait has certain implications, also, for variation: ‘natural selection may have constrained the trait overall, selection tolerates enough variation that with many contributing genes, each potentially varying, different genotypes can produce a long face or thick enamel.’ There are many ways to get a particular skin colour or size of nose or body proportion. But there are also more places that a mutation might affect a particular trait; as Weiss explains, ‘More mutations, means more variation, which means more complexity.’

Part of the point is that we can’t tell, from a particular trait, what gene necessary underlies its characteristics; if any number of different genes may have contributed to a single trait, than the ‘same’ phenotype may be produced in a number of ways. Weiss offers the example of malaria resistance in populations in Africa, Southeast Asia, and India; the genetic mechanisms for resistance produced by natural selection vary because the underlying genetic variation also varied. In addition, if one gene is ‘holding’ a trait, the others that contribute to it might be free to vary in ways that, were that gene not conserving the trait, would lead in a different population to a change in the trait.

Weiss provides the following discussion in his conclusion:

Sometimes it seems that in attempting to find the genes ‘‘for’’ a trait of the kinds we’re usually interested in—behavioral, morphological, or otherwise—we’ll either find no genes at all, because most contributing genes have such a small individual effect that we can’t detect it, or we’ll eventually find that because genes interact with each other in so many ways from conception to adult that all genes, like roads, connect to each other. Hundreds of genes, defined in the modern way to include the panoply of functional units encoded in DNA, are expressed in the development of any complex organ. Complex traits are produced by webs of genetic pathways; that is, of interactions among proteins coded by many different genes. These networks provide many alternate potential routes to a given end, whose use may evolve to vary among or even within species.

Although much of the research and many of the ideas Weiss draws upon are increasingly widely known, I think he does a really masterful job pulling it all together. I referred to his work as a kind of ‘post-neo-Darwinism,’ not because it attacks the foundation of neo-Darwinism, but because it is part of a wider constructive critique that shows the neo-Darwinist ur-narrative of selection acting on phenotype affecting underlying genes is overly simplistic.

The complex ‘road to everywhere’ effect that he describes demonstrates very compellingly that a clear awareness of genetic contributions to traits and an understanding of genetic-level processes that help to produce traits leads us away from a simplistic genetic determinism. The more we understand how genes work, the less likely we are to find certain kinds of evolutionary accounts compelling because we can’t help but realize that the assumptions made about genetic mechanisms in these explanations simplify how genes interact and contribute to phenotypic traits.

Much like our discussion of the ‘human super-organism,’ we get a much more interesting picture of an organism, not carved in genetic stone or predestined ‘nature’ by natural selection, but generated by both long-term evolutionary processes and shorter-term environmental and developmental processes.

References
Weiss, Kenneth M. 2008. All Roads Lead to. . .Everywhere?: Is the genetic basis of interesting traits so complex that it loses much of its traditional evolutionary meaning? Evolutionary Anthropology 17(1):88–92. DOI 10.1002/evan.20156