A paper recently appearing in Science (Näsvall et al. 2012) offers a new insights into the mechanisms by which gene duplication can lead to new genes, gene products, and functions.  The new scheme is termed the innovation-amplification-divergence (IAD) model. 

The possible relevance of gene duplication to evolution was first noted no later than 1932 when JBS Haldane published his book “The Causes of Evolution.”  In this volume, Haldane offered a strong defense of Darwin’s evolutionary ideas, provided some of the foundations for population genetics, and speculated that duplicated genes might offer the advantage of mutating without the usual magnitude of risk for deleterious effects.  Of course, these ideas were being proposed more than a decade before Avery and colleagues offered evidence that DNA was the genetic material (1944). 

Some years later, Susumu Ohno gained fame in evolutionary biology circles for his proposal that a new function could arise through a process that begins with the duplication of a gene (1970).  The argument advanced by Ohno, which had the advantage over Haldane’s earlier proposal that Ohno knew more precisely what constitited a gene and what physically corresponded to a mutation, was that the “extra” copy of the duplicated gene was then free to mutate in ways that could lead to a new biochemical activity.  This scheme was largely accepted as a working hypothesis in the decades since its promulgation.   

While the basic notion of evolution by gene duplication is consistent with much genomic evidence, questions arise as to the precise details.  Two of the authors of the above-cited Science paper, Roth and Andersson, reasonably wondered how a new copy of a gene would be retained long enough in a genome to acquire a new function.  Both of these microbiologists had previously noted that genomic duplications typically imposed fitness costs and were unstable (Reams et al., 2010; Pettersson et al., 2009).  Therefore they questioned whether a duplicate copy of a gene could survive selection long enough to evolve a new biochemical role as Ohno’s model supposed. 

Their insights led them to the idea that perhaps evolution by gene duplication would be more likely if the gene product encoded by a duplicated gene expressed two activities that could be regarded as primary and secondary.  If conditions offered a selective advanatage for the expression of the secondary, as well as primary biochemical activities associated with the original gene, then following a duplication of a locus, mutations that enhanced the secondary activity could proceed in one copy of the gene irrespective of consequences for the primary activity.  The two copies might then diverge and specialize. 

Roth and Andersson and their colleagues tested these ideas by investigating a spontaneous mutant of a gene involved in histidine (His) biosynthesis in Salmonella enterica.  They selected a variant of this gene that also exhibited modest activity in tryptophan (Trp) biosynthesis.  Interestingly, two separate mutations were required to produce a gene product that maintained both His and Trp biosynthetic activity.  One mutation endowed the enzyme with the activity relevant to Trp biosynthesis, but inactivated the His-related activity, and the second mutation restored the His-biosynthetic activity.  

The authors then placed this dual-function gene in a plasmid in S. enterica and subjected the bacteria to selection for improved growth.  Over several hundred generations of selection, the growth rate improved from about 5 hours per cell division to 1.9 – 2.5 hours per division.  Expression of the gene increased in many of the cultures as a consequence of duplication of the relevant portion of the plasmid.  

After as many as 3,000 generations of evolution, a variety of outcomes were observed in the evolved genes.  These genes exhibited increased His-biosynthetic activity and loss of Trp-biosynthetic activity, increased Trp-biosynthetic activity and loss of His-biosynthetic activity, or moderately increased His- and Trp-biosynthetic activities.  Some clones had one copy each of both of the first two “re-specialized” genes. Thus, some of the results were consistent with the IAD model. 

Of course, last month I briefly described the results of Lenski and colleagues (2012) who offered an alternative three-step model of bacterial evolution involving gene amplification.  Their three steps were: 1) potentiation, 2) actualization, and 3) refinement, or the PAR model.  These models are not identical but are not completely incompatible.  There is unlikely to be a single rigid pathway by which new genes, gene products, and molecular functions arise.  Understanding of these processes can be expected to continue evolving.


Näsvall J, Sun L, Roth JR, Andersson DI. Real-time evolution of new genes by innovation, amplification, and divergence. Science. 2012 Oct 19;338(6105):384-7.  doi: 10.1126/science.1226521. PubMed PMID: 23087246.

Haldane. J.B.S. The Causes of Evolution. Longmans and Green, London, 1932.

Avery OT, Macleod CM, McCarty M. Studies on the chemical nature of the substance inducing transformation of pneumococcal types: induction of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus Type III.. J Exp Med. 1944 Feb 1;79(2):137-58. PubMed PMID: 19871359; PubMed Central PMCID: PMC2135445.

Ohno, S. Evolution by Gene Duplication. Spinger, New York, 1970.

Pettersson ME, Sun S, Andersson DI, Berg OG. Evolution of new gene functions:simulation and analysis of the amplification model. Genetica. 2009 Apr;135(3):309-24. Epub 2008 Jun 22. PubMed PMID: 18568430.

Reams AB, Kofoid E, Savageau M, Roth JR. Duplication frequency in a population of Salmonella enterica rapidly approaches steady state with or without recombination. Genetics. 2010 Apr;184(4):1077-94. Epub 2010 Jan 18. PubMed PMID:20083614; PubMed Central PMCID: PMC2865909.

Blount ZD, Barrick JE, Davidson CJ, Lenski RE. Genomic analysis of a key innovation in an experimental Escherichia coli population. Nature. 2012 Sep 27;489(7417):513-8. doi: 10.1038/nature11514. Epub 2012 Sep 19. PubMed PMID:22992527; PubMed Central PMCID: PMC3461117.