Joined: May 2002
And in the "duplicated genes aren't necessarily selectively neutral, dammit" category:
Genome Biol 2002;3(2):RESEARCH0008
Selection in the evolution of gene duplications.
free online at pubmed central
Kondrashov FA, Rogozin IB, Wolf YI, Koonin EV.
National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD 20894, USA. firstname.lastname@example.org
BACKGROUND: Gene duplications have a major role in the evolution of new biological functions. Theoretical studies often assume that a duplication per se is selectively neutral and that, following a duplication, one of the gene copies is freed from purifying (stabilizing) selection, which creates the potential for evolution of a new function. RESULTS: In search of systematic evidence of accelerated evolution after duplication, we used data from 26 bacterial, six archaeal, and seven eukaryotic genomes to compare the mode and strength of selection acting on recently duplicated genes (paralogs) and on similarly diverged, unduplicated orthologous genes in different species. We find that the ratio of nonsynonymous to synonymous substitutions (Kn/Ks) in most paralogous pairs is <<1 and that paralogs typically evolve at similar rates, without significant asymmetry, indicating that both paralogs produced by a duplication are subject to purifying selection. This selection is, however, substantially weaker than the purifying selection affecting unduplicated orthologs that have diverged to the same extent as the analyzed paralogs. Most of the recently duplicated genes appear to be involved in various forms of environmental response; in particular, many of them encode membrane and secreted proteins. CONCLUSIONS: The results of this analysis indicate that recently duplicated paralogs evolve faster than orthologs with the same level of divergence and similar functions, but apparently do not experience a phase of neutral evolution. We hypothesize that gene duplications that persist in an evolving lineage are beneficial from the time of their origin, due primarily to a protein dosage effect in response to variable environmental conditions; duplications are likely to give rise to new functions at a later phase of their evolution once a higher level of divergence is reached.
Thus, the observation that purifying selection appears to act on all recent duplicates and examination of the functions of recently duplicated genes do not support the notion that gene duplication results in true functional redundancy and duplications may achieve fixation despite being redundant . The alternative hypothesis - that gene duplications are fixed in a population by positive selection in all organisms - is supported by a combination of evidence of adaptive duplications from many types of living organisms: prokaryotes [31,33,45,46,48,50,55,56], protists [35,58,59], plants [39,44], fungi [43,49], invertebrates [40,41,51,52,53], non-mammalian vertebrates , as well as mammalian somatic tissues [34,36,37,38]. Combining these observations with the suggestion that gene duplication may be a general mechanism of adaptation to various conditions of environmental stress [32,33,46,48,49,50,52,53,55,60], we suggest that, in both prokaryotes and eukaryotes, most paralogs that are fixed in a population have a direct effect on fitness from the moment of duplication, and aid in the adaptation to various environmental conditions, primarily through a protein dosage effect.
That the short-term benefit of a gene duplication is a direct effect on protein dosage also stems from a variety of experimental observations in a number of organisms, prokaryotic and eukaryotic. Gene duplication may be a temporary mechanism to increase protein or RNA dosage, as in the case of rRNA genes in amphibian oocytes and ciliate macronuclei, the chorion genes in some dipterans, actin genes in chicken as well as drug transporters in somatic tissues (see [34,37] for reviews). Protein dosage effects have also been demonstrated in a number of other studies of inheritable adaptive gene duplications [32,34,35,43,44,46,49,51,53,61]. Furthermore, there is evidence from the analysis of the yeast genome that duplicated genes tend to be from those sets of functions that are more highly expressed , supporting a general role for selection on protein dosage in duplicated genes.
The present observation that duplicated genes experience a substantial relaxation of selection compared to unduplicated genes is compatible with the traditional view that gene duplications make a major contribution to the evolution of new gene functions. Additionally, the repertoire of protein functions among recent duplicates suggests that many gene duplications contribute to adaptation of the organism to various forms of environmental stress. The results of the present analysis of recent duplications suggest a two-stage evolutionary model of gene duplication: in the first stage, immediately after duplication and during the early phase of their evolution, paralogs are retained and are subject to purifying selection because of the short-term advantage of protein dosage regulation; at a later stage in their evolution, gene duplications are likely to provide a long-term advantage by enabling the creation of new functions.
What would be interesting to know would be the relative roles of regulation mutations vs. gene duplications in effecting adaptation (via amount of proteins produced) to changing conditions as discussed above. One would think that regulatory changes would be the more "elegant" or "efficient" way to adapt, but apparently evolution doesn't know or care, at least sometimes...
(it may be that regulatory changes have a "limit" that could only be exceeded by duplicating the gene...but now I'm at the limits of my knowledge...)
(PS: The assumption that duplicating a gene doubles the level of a particular protein may not be a good one, particularly if the expression of the gene is regulated by some kind of feedback mechanism...just something to keep in mind)