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LONG TERM EVOLUTION IS MORE THAN A SUM OF INDIVIDUAL MUTATIONS
Researchers from the Centre for Genomic Regulation publish their work in Nature where they show that a fraction of the evolution occurs as a result of a combination of two individually deleterious mutations.
The work goes beyond a typical interpretation of macroevolution and demonstrates how deleterious mutations, which are generally thought not to contribute to the evolutionary process, could have an important role in evolution.One of the hallmarks of Darwinian thinking is the notion that evolution is a gradual process consisting of consecutive fixations of mutations of small effects and that such consecutive mutational steps give rise to complex adaptations and explain the diversity of species. Since Darwin’s thoughts on evolution were primarily concerned with the macroevolutionary scale, the step-by-step transition from one form to another became synonymous with his theory. The Modern Synthesis united Darwinian evolution with genetics and population genetics theory, yet macroevolution as a series of consecutive steps remains a pervasive paradigm.The underlying assumption of such step-by-step macroevolution is that each individual step confers an adaptive advantage or at least is not deleterious. However, theory developed by Motoo Kimura in 1985 proposed an alternative. Kimura considered a case of compensatory evolution, where the fitness effects of alleles at two loci are co-dependent, such that the contribution of allele A to fitness is positive when it is present at both loci and the fitness contribution of allele a is positive when they occupy both of the loci. Thus, genotypes AA and aa confer high fitness while genotypes Aa and aA have low fitness. If the fitness of Aa and aA genotypes is low enough it would be impossible to evolve from AA to aa by single mutational steps, unless two mutations A -> a occur at the same time. However, by taking into account population variation Kimura showed that the probability of evolving from AA to aa is much larger than a simple probability of a double mutation. Because the evolutionary unit is a population, even a deleterious genotype can persist in a population for a short period of time. Thus, a population is unlikely to be uniformly AA, but also will include a few Aa and aA genotypes. If the second mutation occurs in either Aa or aA genotype, an aa genotype is created that is no longer deleterious and may be fixed in the population. Thus, the transition from AA to aa can occur without ever fixing the Aa or aA intermediate genotype, essentially skipping a beat in the step-by-step analogy of macroevolution.The work of the Centre for Genomic Regulation and University of Michigan researchers was concerned with evolution of a section of mitochondrial transference RNAs. They considered switches between AU and GC Watson-Crick pairs in such structures and have showed that the intermediate states of GU and AC are deleterious. Their data, concerned both with between-species differences and within-species variation, are consistent with Kimura’s model of compensatory evolution. Because such compensatory switches comprise a majority of all substitutions in these structures they show that an entire class of molecules evolves not by the commonly assumed step-by-step mode of evolution, but rather through a process where each evolutionary step is composed of two individual mutations that are fixed in a single event. The researchers said that “As compelling as the step-by-step model of Darwinian evolution is, it seems that at least for stems of mt-tRNAs a majority of substitutions involve population dynamics that allow a population to jump throw a better fitness”.“Our work shows that it is impossible to describe the long-term evolution of an entire class of molecules (mitochondrial tRNAs) without understanding how different polymorphisms interact with each other in the same population” says Fyodor Kondrashov, principal investigator of this paper and group leader of the Evolutionary Genomics group at the CRG. “Our findings show that some deleterious mutations are not necessarily evolutionary dead ends. Rather, two individually deleterious mutations that are benign when combined within one genome provide novel paths for evolution to proceed forward” explains Kondrashov.Reference work: Margarita V. Meer, Alexey S. Kondrashov, Yael Artzy-Randrup & Fyodor Kondrashov (2010) “Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness”. Nature. DOI: 10.1038/nature08691. 
For further information: Laia Cendrós, Communication & PPRR Dept., Centre for Genomic Regulation (CRG), Dr. Aiguader, 88 – Edif. PRBB, 08003 Barcelona. Tel. +34 93 316 02 37, laia.cendros@crg.es