I’m starting my first post by looking at a recent paper in Science.
Paper: “New Genes in Drosophila Quickly Become Essential”, Chen et. al. Science.
Background: We’ve all heard the statistics that if you take our genomes and compare it those of chimpanzees or mice, the genomes are not all that different (over 97-99% depending on the metrics [1]). But that begs the question – how can such small differences explain the large differences in phenotype and function? (We can even ask if there are even that many differences in function?). The answer might lie in the fact that not all of our 25k genes are created equal. Some are definitely more essential than others – evidence suggest that there are ‘ultraconserved’ genes that could possibly be very essential [2] .
So, it means that essential genes are “conserved and ancient” right? It can’t be that easy for a gene or a random piece of DNA sequence to become functional, much less essential..This new paper however provides evidence in flies that this might not be the case.
Summary: This paper shows that many young genes (with an origin of 3-35 million years ago) in a species of flies (Drosophila) become essential fast. Young genes can arise through several mechanisms, summarized well here and in the below Figure’s part C. In this case, they take ‘essential’ to mean essential for survival. They first identify ‘young’ genes and dating their origin by comparing genes to their paralog in other related fly species. Then, they make flies that don’t have these essential genes and see if, when, and where these flies die [3].
Results and Implications: They have a few results, but there were two in particular that I found interesting:
- The number of genes that become essential is around the same as old genes (30%). This leads to the main implication which is the namesake of the paper – the same proportion of genes are essential independent of their time of origin, i.e. young genes become essential fast. Future experiments will tell us whether this is true for other species or if it is specific to flies. Maybe the more complex an organism is, the harder it is for a gene to become essential or the longer it takes?
- The young essential genes were lethal at a later point in development (pupal as opposed to larval) than old essential genes. This is an interesting result. What this could mean is that younger genes become integrated quickly into important pathways in the fly, but it’s harder to integrate into the really important pathways early in development. This could provide evidence to the hypothesis that there are different levels of essentially of genes. There could be biological mechanisms that prevent the ‘really important’ code from being tinkered with. These are open questions.
There was also a brief discussion on neofunctionalization vs. subfunctionalization, but I believe that their conclusion was based on weak evidence so I won’t go into it here [4].
Notes:
[1] The metric can be looking at substitutions, insertions, deletions, or combinations of those.
[2] One way to infer functionality is conservation. It is posited that deep conservation could imply deep function.
[3] They can only experiment with some of these genes, because the way they knock-out these genes is through RNAi and they don’t consider young genes where RNAi takes out other targets as well.
[4] When there is a gene duplication event, the new gene can take on the same function as the original gene (if both genes remain function, this provides redundancy; there is some evidence for this) or the two genes can evolve different functions . Here is a diagram that illustrates the difference between the neofunctionalization and subfunctionalization for this. The paper claims that whether a young gene is essential is independent of the old gene’s essentiallity – but I don’t think this claim can be made given the small sample size (there seems to be a bias towards an essential gene coming from an essential parent). They take this to then provide evidence for the neofunctionalization origin of most new protein-coding genes.
