Role of selection in fixation of gene duplications

F. Kondrashov, A. Kondrashov, Journal of Theoretical Biology 239 (2006) 141–151.

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Abstract
New genes commonly appear through complete or partial duplications of pre-existing genes. Duplications of long DNA segments are constantly produced by rare mutations, may become fixed in a population by selection or random drift, and are subject to divergent evolution of the paralogous sequences after fixation, although gene conversion can impede this process. New data shed some light on each of these processes. Mutations which involve duplications can occur through at least two different mechanisms, backward strand slippage during DNA replication and unequal crossing-over. The background rate of duplication of a complete gene in humans is 10-9-10-10 per generation, although many genes located within hot-spots of large-scale mutation are duplicated much more often. Many gene duplications affect fitness strongly, and are responsible, through gene dosage effects, for a number of genetic diseases. However, high levels of intrapopulation polymorphism caused by presence or absence of long, gene-containing DNA segments imply that some duplications are not under strong selection. The polymorphism to fixation ratios appear to be approximately the same for gene duplications and for presumably selectively neutral nucleotide substitutions, which, according to the McDonald-Kreitman test, is consistent with selective neutrality of duplications. However, this pattern can also be due to negative selection against most of segregating duplications and positive selection for at least some duplications which become fixed. Patterns in post-fixation evolution of duplicated genes do not easily reveal the causes of fixations. Many gene duplications which became fixed recently in a variety of organisms were positively selected because the increased expression of the corresponding genes was beneficial. The effects of gene dosage provide a unified framework for studying all phases of the life history of a gene duplication. Application of well-known methods of evolutionary genetics to accumulating data on new, polymorphic, and fixed duplication will enhance our understanding of the role of natural selection in the evolution by gene duplication.
Publishing Year
Date Published
2006-03-21
Journal Title
Journal of Theoretical Biology
Volume
239
Issue
2
Page
141 - 151
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Kondrashov F, Kondrashov A. Role of selection in fixation of gene duplications. Journal of Theoretical Biology. 2006;239(2):141-151. doi:10.1016/j.jtbi.2005.08.033
Kondrashov, F., & Kondrashov, A. (2006). Role of selection in fixation of gene duplications. Journal of Theoretical Biology, 239(2), 141–151. https://doi.org/10.1016/j.jtbi.2005.08.033
Kondrashov, Fyodor, and Alexey Kondrashov. “Role of Selection in Fixation of Gene Duplications.” Journal of Theoretical Biology 239, no. 2 (2006): 141–51. https://doi.org/10.1016/j.jtbi.2005.08.033.
F. Kondrashov and A. Kondrashov, “Role of selection in fixation of gene duplications,” Journal of Theoretical Biology, vol. 239, no. 2, pp. 141–151, 2006.
Kondrashov F, Kondrashov A. 2006. Role of selection in fixation of gene duplications. Journal of Theoretical Biology. 239(2), 141–151.
Kondrashov, Fyodor, and Alexey Kondrashov. “Role of Selection in Fixation of Gene Duplications.” Journal of Theoretical Biology, vol. 239, no. 2, Elsevier, 2006, pp. 141–51, doi:10.1016/j.jtbi.2005.08.033.

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