The 19th century must have been an exciting time to be a biologist, or a natural historian, adhering to the terminology of that time. These were the naturalists who unearthed fossils of giant reptiles and discovered what living cells are made off under their microscopes. One of the finest natural historians to have ever lived, lived in this century. He managed to incorporate observations from fields as different as paleontology and comparative anatomy into a single, coherent framework. His name was Charles Darwin, his theory was evolution.
Embryology was one of the fields of natural science where Darwin found evidence for the common descent of species. Darwin noted that it was nearly impossible to find differences between the embryos of young of closely related species or breeds. In short, the more general properties of organisms are the first to develop, while species-specific properties develop later (sometimes as late as adolescence or early adulthood). One of the most famous and most replicated illustrations of this principle is the one Ernst Haeckel drew in his Antropogenie (1874). Although it has been shown now that the drawings are not at all correct, the general principle holds and the figure is still widely used in biology textbooks (even my high-school biology book had one!).
The embryos of 8 species are compared at three different stages of development: fish, salamander, turtle, bird, pig, cow, rabbit and human. The embryos differ more from each other in the later stages, than in the earlier stages (Ernst Haeckel, Antropegenie, 1874)
While these morphological observations are of course interesting, a 21st century biologist wants to find the genomic basis that is responsible for this phenomenon! That must be what Roux and Robinson-Rechavi thought when they published their study in 2008 in PLoS Genetics. By analyzing the gene expression during embryonal development in mice and zebrafish, they found that genes that are expressed earlier in development are evolutionary ‘more constrained’ during evolution compared to genes that are expressed later on. They came to this conclusion when they saw that when you remove an ‘early gene’, it is more likely to have fatal effects on the embryo. The sequences of these ‘early genes’ are also more conserved than that of ‘later genes’. Not only did they study the removal of developmental genes: since the entire genome of the ancestor of bony fishes (which includes the zebrafish) got duplicated at a certain time, Roux and Robinson-Rechavi could also investigate what happened to early developmental genes when they get duplicated. It turns out that duplicated early genes have subsequently been lost again more times than genes that are active later in development. Based upon this evidence they concluded that genes active in early development are heavily constrained during evolution: both removal and duplication of such genes reduces the fitness of the organism.
In a paper published this month in Genome Biology & Evolution, Milinkovitch and colleagues build upon these findings (seriously, check out the names of both papers!). They wondered whether these genomic constraints on evolution could also be related to the age of the genes. Milinkovitch defines the age of a gene as how long ago the gene appeared for the first time in the history of animal evolution. They compared this age to the tissue specificity of these genes: in how many tissues are those genes expressed nowadays. They found a clear correlation between the age of a gene and the number of tissues it is expressed in. Really old genes are more likely to be expressed in a wide variety of tissues (like your brain, your liver and your left small toe), whereas younger genes are specific to certain tissues. In the paper, several possible explanations are given for this observation:
This striking pattern might have been brought about by various … mechanisms, including 1) broadening of gene expression through evolutionary time, 2) a tendency for duplicates to subfunctionalize, and 3) the differentiation of an increasing number of cell types and anatomical systems through evolutionary time.
The authors do not find conclusive evidence for any of the three scenario’s, but it’s nevertheless interesting to speculate about the underlying cause(s). In such complex systems, I would not be surprised if all mechanisms contribute in varying degrees to this effect.
In this figure, the red line shows the mean number of tissues a gene is expressed in respect to the time the gene first appeared.The blue line shows the average number of cell types over evolutionary time, in the human lineage. Figure taken from reference 2.
This type of reasearch has only become possible because new technologies allow researchers to sequence entire genomes and follow gene expression of a large set of genes over long periods of time. I can only imagine how the 19th century naturlists would have loved to learn about these new findings. I think they would be pleased to learn that their theories and observations still captivate and inspire researchers today. Standing on the shoulders of giants indeed!
Citations:
Roux J, & Robinson-Rechavi M (2008). Developmental constraints on vertebrate genome evolution. PLoS genetics, 4 (12) PMID: 19096706
Milinkovitch, M., Helaers, R., & Tzika, A. (2009). Historical Constraints on Vertebrate Genome Evolution Genome Biology and Evolution, 2010, 13-18 DOI: 10.1093/gbe/evp052