Plus c'est la même chose, plus ça change??

Nothing ever really changes, or so goes the old French saying 'plus ça change, plus c'est la même chose.' The more things change, the more they're the same thing. But is that how life really is?

An interesting new paper in Genome Research on this subject is getting some notice, but in fact the results should not be surprising, given what is known about evolution and development.

The blurb in Nature says:

The earliest stages of embryo development [as shown in the photo above, taken from the paper] seem to be almost identical among mammals. However, Sheng Zhong at the University of Illinois at Urbana-Champaign and his team have found that 40.2% of the genes shared by humans, mice and cows are expressed differently at this point.

Their analysis of gene-expression patterns in embryos at various stages early in development showed that differences result from altered gene regulation. In some cases, mutations affected the binding of regulatory proteins. In others, transposons or 'jumping genes' had hopped in front of the genes, changing their regulation.

This variation among species suggests that multiple gene networks can guide embryo development, and could be harnessed to generate embryonic stem cells.

This may have significant implications for stem cell research, but it also says a lot about evolution and development (EvoDevo). People are often surprised to learn that traits that are similar between species can have very different genetic architecture -- it's more usual to hear about homologous or orthologous genes, similar genes for similar traits (the iconic example is Hox genes, which play a major role in body patterning in fruit flies and humans, and every species in between).

Alternatively, a story in the New York Times last week described the usefulness of yeast or plants or worms for finding genes for human diseases. The genes described belong to clusters that do completely unrelated things in different organisms (one example was of a cluster of genes that repair damage to the cell wall in yeast but that is involved in blood vessel formation in humans). These clusters have been conserved through evolutionary time.

But the idea that different genes can underlay homologous traits is perhaps more counter-intuitive. Ken and his then post-doc, Malia Fullerton, published a paper in Theoretical Population Biology in 2000 describing just this. The effect is called 'phenogenetic drift' to indicate that the trait's genetic basis, the genetic effects that generate the phenotype, changes. This is not the same as genetic drift, when genetic variation that has no effect on a trait, or at least on reproductive success ('fitness') changes over the generations, nor that of phenotypic drift, when traits vary over generations to the extent that the variation doesn't affect reproductive success. Phenogenetic drift can be these things, but also, and perhaps most importantly, it occurs even when there is selection affecting the trait, even strong selection.

Thus, in the example above, the very early and hence very fundamentally important, stages in mammalian embryos are quite similar among different species, but the usage of genes to make it so is considerably different. Phenogenetic drift is easy to see all over the place -- even within species, when different people can have the same trait -- even including disease -- for different genetic reasons. Relative to each other these genotypes are equivalent in fitness terms, and their contributing alleles will change frequency over time by drift. It's no surprise to see it when we know that duplicate genes and many contributing genes together generate lots of redundancy and alternative genetic pathways to get the same trait.

However the dogma about selection and adaptive evolution has been gene- rather than trait-centered. But when many different genotypes can generate effectively the same phenotype, then perhaps genes really aren't the most important things to consider when we try to understand evolution. In this sense, perhaps because genes weren't understood at the time and perhaps because he had it right, Darwin developed his ideas about phenotypes -- the traits of organisms -- rather than genotypes. After all, he didn't need his idea of genetics to explain the historical nature of life's variation (indeed, evolution as he saw it wouldn't work under his idea of inheritance, and he knew it).

It often seems that the longer a trait is maintained, the more likely it is to have changed its genetic basis. Kazu Kawasaki in our lab, for example, has written a number of papers about the different genetic architecture for bone and tooth mineralization that has evolved in different lineages. In that case, the gene pathways share a common ancestor, a single gene that duplicated in different lineages to create gene families involved in mineralization -- he calls these the SCPP gene family. The original founding gene was apparently involved in the development of the first vertebrate mineralized skeletal tissue (probably, external skeletal protective plates or scales, even before there were calcified bones).

The final composition and structure of mineralized bone may vary, but it's the same trait, and serves essentially the same purpose (strength) in different lineages. Same trait, different genes. Whether this is usually true with conservation of form within lineages (such as the ants in amber that we wrote about last week), we can't know, because we have no way to know the original genetic basis. However, among other things, phenogenetic drift or alternative genomic pathways to the same trait, has interesting implications for notions of homology, the sharing of traits today because they have descended from the same ancestor. Traits can be homologous, but their genetic basis may not be. When selection is on the phenotype, it gets maintained however works!