Pseudogenes, which are in essence regions of the genome that used to be genes but no longer able to produce a functional unit, have long been considered to be models of the genetic equivalent of Switzerland's neutrality. With this assumption of neutrality in hand, researchers have used studies of pseudogenes to better understand what happens to DNA when it is not visible to any form of natural selection. That is, pseudogenes have been thought to be neither harmful (as in, they are not under negative selection) or helpful (i.e., they are not under positive selection).
And from this assumption we have supposedly learned about mutation rates and patterns (because if they are neutral then the changes in pseudogenes should be reflective of mutational processes, not selection) as well as all sorts of other features of genome evolution.
Over the years, some have challenged the assumption of neutrality of pseudogenes (e.g., see here) like many have questioned whether Switzerland is really neutral. But overall, the feeling that pseudogenes were mostly neutral seems to have stuck. However, that may change a bit with a new paper from Chih-Horng Chu and Howard Ochman in PLoS Genetics (PLoS Genetics: The Extinction Dynamics of Bacterial Pseudogenes).
In their paper they report: (this is their authors summary)
Pseudogenes have traditionally been viewed as evolving in a strictly neutral manner. In bacteria, however, pseudogenes are deleted rapidly from genomes, suggesting that their presence is somehow deleterious. The distribution of pseudogenes among sequenced strains of Salmonella indicates that removal of many of these apparently functionless regions is attributable to their deleterious effects in cell fitness, suggesting that a sizeable fraction of pseudogenes are under selection.
Basically, what they did was the following
1. Compare Salmonella genomes. Identify putative pseudogenes and trace their evolution onto a phylogeny of the species.
Figure 1. Distribution of pseudogenes among Salmonellagenomes.
The phylogenetic tree was inferred from 2,898 single-copy genes shared by all fiveS. enterica subsp. enterica strains and the outgroup S. enterica subsp. arizonae.doi:10.1371/journal.pgen.1001050.g001
2. Carry out a variety of analyses of the pseudogenes such as
- looking at ratios of Ka/Ks (this is in essence a ratio of amino acid changes - aka non synonymous substitutions to "silent" synonymous changes which occur when the DNA sequence changes but the same amino acid is encoded).
- examining the types and frequencies of gene inactivating mutations
3. Then they looked at the "ages" of pseudogenes - with age being estimated by the position in the tree in which the pseudogenes appear to have arise.
4. Finally the examined the age class distribution of pseudogenes as well as whether there were other differences between pseudogenes of different ages. And what they found was inconsistent with a neutral model. Instead, what they conclude is that something is making it advantageous to delete pseudogenes more rapidly than one might expect.
What explains this? After testing multiple possibilities the authors conclude that their is some negative selection against pseudogenes (or I guess positive selection for deletion of pseudogenes).
They conclude by suggesting this is likely to be pervasive across all bacteria and even in archaea. And furthermore make a connection to possible selection on intron size in eukaryotes. Anyway - the paper seems quite interesting and worth a read. Still pondering what it all means, so I would welcome comments.
Kuo, C., & Ochman, H. (2010). The Extinction Dynamics of Bacterial Pseudogenes PLoS Genetics, 6 (8) DOI: 10.1371/journal.pgen.1001050