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Open AccessOpinion

Natural Knockouts: Natural Selection Knocked Out

The Independent Research Initiative on Information & Origins, 79540 Loerrach, Germany
Academic Editor: Hirofumi Akari
Biology 2017, 6(4), 43; https://doi.org/10.3390/biology6040043
Received: 13 September 2017 / Revised: 17 October 2017 / Accepted: 25 October 2017 / Published: 12 December 2017
(This article belongs to the Special Issue Biology in the Early 21st Century: Evolution Beyond Selection)
In functional genomics studies, research is dedicated to unveiling the function of genes using gene-knockouts, model organisms in which a gene is artificially inactivated. The idea is that, by knocking out the gene, the provoked phenotype would inform us about the function of the gene. Still, the function of many genes cannot be elucidated, because disruption of conserved sequences, including protein-coding genes, often does not directly affect the phenotype. Since the phenomenon was first observed in the early nineties of the last century, these so-called ‘no-phenotype knockouts’ have met with great skepticism and resistance by died-in-the-wool selectionists. Still, functional genomics of the late 20th and early 21st centuries has taught us two important lessons. First, two or more unrelated genes can often substitute for each other; and second, some genes are only present in the genome in a silent state. In the laboratory, the disruption of such genes does not negatively influence reproductive success, and does not show measurable fitness effects of the species. The genes are redundant. Genetic redundancy, one of the big surprises of modern biology, can thus be defined as the condition in which the inactivation of a gene is selectively neutral. The no-phenotype knockout is not just a freak of the laboratory. Genetic variants known as homozygous loss-of-function (HLOF) variants are of considerable scientific and clinical interest, as they represent experiments of nature qualifying as “natural knockouts”. Such natural knockouts challenge the conventional NeoDarwinian appraisal that genetic information is the result of natural selection acting on random genetic variation. View Full-Text
Keywords: genetic redundancy; natural knockout; natural selection; homozygous loss-of-function genetic redundancy; natural knockout; natural selection; homozygous loss-of-function
MDPI and ACS Style

Borger, P. Natural Knockouts: Natural Selection Knocked Out. Biology 2017, 6, 43.

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