Evolutionary impact of copy number variation rates
© The Author(s) 2017
Received: 23 June 2017
Accepted: 8 August 2017
Published: 10 August 2017
Copy number variation is now recognized as one of the major sources of genetic variation among individuals in natural populations of any species. However, the relevance of these unexpected observations goes beyond diagnosing high diversity.
Here, it is argued that the molecular rates of copy number variation, mainly the deletion rate upon variation, determine the evolutionary road of the genome regarding size. Genetic drift will govern this process only if the effective population size is lower than the inverse of the deletion rate. Otherwise, natural selection will do.
The advent of genomic systems biology is leading, in very recent years, to the discovery of widespread genetic features, previously unrecognized in complex organisms like humans; they can then have strong implications in biomedicine. One of these fascinating features is copy number variation , which is already considered one of the major sources of genetic variation. Thereby, in natural populations, some individuals have significant portions of the genome repeated, even entire genes, something until now believed to occur at a large scale only in microbes . Recently, genomic studies with populations of different model organisms are serving to estimate copy number variation rates [1, 3], revealing great differences among them. However, the generation of genetic diversity, here genome rearrangements, cannot be fully understood without accounting for an evolutionary perspective . In this regard, what is the impact of these rates?
In this short piece, it is argued that these rates greatly determine the way by which the genome can increase its size, i.e., the evolutionary force that controls this process. Indeed, the acquisition of genetic redundancy is believed to be the major mechanism to increase genome size, and then genome complexity [5, 6]. For that, duplications have to be fixed in the population, a process that mainly occurs, according to the classical theory, by random genetic drift under effectively neutral selective conditions thanks to a reduction in effective population size . However, the balance between duplication and deletion, at a given locus, regulates the power of drift in fixation, as it is illustrated here with a simple quantitative analysis.
Fixation will occur in displacements that reach x = 1 [i.e., Δx = λ/(μ + λ)], which yields the condition of λN < 1/12, when λ ≫ μ (typically in nature) . Fluctuations can even be three times the typical value, although they will occur sporadically. This yields the soft condition of λN < 1 to have chances for fixation. By contrast, if (μ + λ)N ≫ 1, the system is mostly dominated by the balance between duplication and deletion. Therefore, Δx ≪ 1, which entails that duplications cannot be fixed.
The deletion rate that was considered here is the rate at which a repeated portion of the genome is deleted. Certainly, duplication imposes a genetic instability that is generally resolved by deletion ; sometimes by other means, like relocation . Experimentally, such a deletion rate needs to be estimated from populations with individuals carrying duplications. The deletion rate of significant, but unique fragments is expected to be only a lower bound. Despite, this has already been proposed as a determinant of genome size .
But the rates (μ and λ) confidently estimated until now (in mutation accumulation experiments) are really scarce, only available for some model organisms . In addition, the deletion rates might be underestimated (see “Remark”). For Arabidopsis thaliana, e.g., only bioinformatic estimates have been produced, although these give values that differ from experimental estimates in several orders of magnitude. Based on the values of D. melanogaster and C. elegans, one can predict λ ≈ 10−7–10−6/locus/gen. for A. thaliana, resulting in λN ≈ 0.03–0.3 < 1, as N ≈ 3·105. Higher eukaryotes have indeed more chances to transiently fix duplications by drift due to a reduced effective population size .
Definitely, λN < 1 has to be satisfied in order to reach transient fixation of duplications by genetic drift. Otherwise, the population remains stably polymorphic regarding copy number. If this were the case, positive selective conditions should be invoked to explain an increase in genome size. After all, the precise characterization at the molecular level of the genome rearrangement rates, especially the deletion rate upon duplication, will shed much light to recognize how fortuitous was the path to reach the life that today we see on the Earth .
Simplification to a birth–death process, while genome rearrangements may be more complex processes (e.g., gene relocation in the chromosome to stabilize a duplicate).
No consideration of high-order variations, such as gene triplications or quadruplications, while these are found in nature. No consideration of individuals with zero copies, assuming they are deleterious and then quickly diluted.
Population size assumed constant, while this may vary with time due to multiple environmental factors.
The author declares that he has no competing interests.
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Work funded by the Spanish Ministry of Economy (MINECO/FEDER), Grant BFU2015-66894-P. Support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).
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