Academic journal article Genetics

Mutational Interference and the Progression of Muller's Ratchet When Mutations Have a Broad Range of Deleterious Effects

Academic journal article Genetics

Mutational Interference and the Progression of Muller's Ratchet When Mutations Have a Broad Range of Deleterious Effects

Article excerpt

ABSTRACT

Deleterious mutations can accumulate in asexual haploid genomes through the process known as Muller's ratchet. This process has been described in the literature mostly for the case where all mutations are assumed to have the same effect on fitness. In the more realistic situation, deleterious mutations will affect fitness with a wide range of effects, from almost neutral to lethal. To elucidate the behavior of the ratchet in this more realistic case, simulations were carried out in a number of models, one where all mutations have the same effect on selection [one-dimensional (1D) model], one where the deleterious mutations can be divided into two groups with different selective effects [two-dimensional (2D) model], and finally one where the deleterious effects are distributed. The behavior of these models suggests that deleterious mutations can be classified into three different categories, such that the behavior of each can be described in a straightforward way. This makes it possible to predict the ratchet rate for an arbitrary distribution of fitness effects using the results for the well-studied 1D model with a single selection coefficient. The description was tested and shown to work well in simulations where selection coefficients are derived from an exponential distribution.

(ProQuest: ... denotes formulae omitted.)

POPULATIONS that reproduce asexually can accumulate deleterious mutations in a process now known as Muller's ratchet (MULLER 1964; FELSENSTEIN 1974). When the genomes in the population do not recombine, different mutations that by chance appear in the same genome will remain linked. If back mutations are rare, this linkage will not be disrupted and all mutations segregating together will influence each other. Although selection will hold back the accumulation of deleterious mutations, when by chance in a finite population all mutation-free individuals have been lost they can not be recreated; this is one irreversible "click" of the ratchet. Now the least loaded class carries one mutation and this class can be lost in the same way, leading to further clicks. The irreversibility of the ratchet can lead to a relentless accumulation of deleterious mutations and possibly to the eventual doom of the species. Another effect of the linkage is that the counterselection on deleterious mutations is considerably weakened. This is often expressed as a reduction in effective population size and leads to a much faster fixation of deleterious mutations than in a corresponding population of recombining genomes (CHARLESWORTH and CHARLESWORTH 1997). These are the two main properties of Muller's ratchet: the irreversibility and the reduction of effective selection.

Escaping the ratchet has been discussed as one major advantage of sex and recombination (FELSENSTEIN 1974; MAYNARD SMITH 1978; HURST and PECK 1996; BARTON and CHARLESWORTH 1998; GESSLER and XU 1999; KEIGHTLY and EYRE-WALKER 2000). Furthermore, the degeneration and reduction of the genomes of intracellular symbionts and parasites (MORAN 1996; RISPE and MORAN 2000; PETTERSSON and BERG 2007) as well as organelles (LYNCH 1996; BERGSTROM and PRITCHARD 1998; LYNCH and BLANCHARD 1998; Loewe 2006) have been suggested as consequences of the ratchet. Interestingly, the recent calculations by Loewe (2006) suggest that the human mitochondrial line could have been under serious threat of extinction from the effects of Muller's ratchet. Also the degeneration of the Y chromosome through lack of recombination has been analyzed as an example of Muller's ratchet (RICE 1994; GORDO and CHARLESWORTH 2000a, 2001). Thus, the properties of the ratchet are of fundamental biological relevance and have received considerable attention in the literature.

Deleterious mutations can accumulate also in populations that are of such small size that purifying selection becomes inefficient. However, in such small populations, mutations will become fixed (or lost) relatively fast in comparison to their rate of appearance, and different kinds of mutations will not segregate simultaneously in the population. …

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