Nick Lane

Publications of Nick Lane

• The neglected genome.

  Authors: Graziano Pesole, John F Allen, Nick Lane, William Martin, David M Rand, Gottfried Schatz, Cecilia Saccone

  EMBO reports. 05/2012;

• Evolution. The costs of breathing.

  Authors: Nick Lane

  Science (New York, N.Y.). 10/2011; 334(6053):184-5.

• Mitonuclear match: optimizing fitness and fertility over generations drives ageing within generations.

  Authors: Nick Lane

  BioEssays : news and reviews in molecular, cellular and developmental biology. 09/2011; 33(11):860-9.

  Many conserved eukaryotic traits, including apoptosis, two sexes, speciation and ageing, can be causally linked to a bioenergetic requirement for mitochondrial genes. Mitochondrial genes encodeMany conserved eukaryotic traits, including apoptosis, two sexes, speciation and ageing, can be causally linked to a bioenergetic requirement for mitochondrial genes. Mitochondrial genes encode proteins involved in cell respiration, which interact closely with proteins encoded by nuclear genes. Functional respiration requires the coadaptation of mitochondrial and nuclear genes, despite divergent tempi and modes of evolution. Free-radical signals emerge directly from the biophysics of mosaic respiratory chains encoded by two genomes prone to mismatch, with apoptosis being the default penalty for compromised respiration. Selection for genomic matching is facilitated by two sexes, and optimizes fitness, adaptability and fertility in youth. Mismatches cause infertility, low fitness, hybrid breakdown, and potentially speciation. The dynamics of selection for mitonuclear function optimize fitness over generations, but the same selective processes also operate within generations, driving ageing and age-related diseases. This coherent view of eukaryotic energetics offers striking insights into infertility and age-related diseases.

• Planctomycetes and eukaryotes: a case of analogy not homology.

  Authors: James O McInerney, William F Martin, Eugene V Koonin, John F Allen, Michael Y Galperin, Nick Lane, John M Archibald, T Martin Embley

  BioEssays : news and reviews in molecular, cellular and developmental biology. 08/2011; 33(11):810-7.

  Planctomycetes, Verrucomicrobia and Chlamydia are prokaryotic phyla, sometimes grouped together as the PVC superphylum of eubacteria. Some PVC species possess interesting attributes, in particular,Planctomycetes, Verrucomicrobia and Chlamydia are prokaryotic phyla, sometimes grouped together as the PVC superphylum of eubacteria. Some PVC species possess interesting attributes, in particular, internal membranes that superficially resemble eukaryotic endomembranes. Some biologists now claim that PVC bacteria are nucleus-bearing prokaryotes and are considered evolutionary intermediates in the transition from prokaryote to eukaryote. PVC prokaryotes do not possess a nucleus and are not intermediates in the prokaryote-to-eukaryote transition. Here we summarise the evidence that shows why all of the PVC traits that are currently cited as evidence for aspiring eukaryoticity are either analogous (the result of convergent evolution), not homologous, to eukaryotic traits; or else they are the result of horizontal gene transfers.

• Plastids, genomes, and the probability of gene transfer.

  Authors: Nick Lane

  Genome biology and evolution. 02/2011; 3:372-4.

• The energetics of genome complexity.

  Authors: Nick Lane, William Martin

  Nature. 10/2010; 467(7318):929-34.

  All complex life is composed of eukaryotic (nucleated) cells. The eukaryotic cell arose from prokaryotes just once in four billion years, and otherwise prokaryotes show no tendency to evolve greaterAll complex life is composed of eukaryotic (nucleated) cells. The eukaryotic cell arose from prokaryotes just once in four billion years, and otherwise prokaryotes show no tendency to evolve greater complexity. Why not? Prokaryotic genome size is constrained by bioenergetics. The endosymbiosis that gave rise to mitochondria restructured the distribution of DNA in relation to bioenergetic membranes, permitting a remarkable 200,000-fold expansion in the number of genes expressed. This vast leap in genomic capacity was strictly dependent on mitochondrial power, and prerequisite to eukaryote complexity: the key innovation en route to multicellular life.

• How did LUCA make a living? Chemiosmosis in the origin of life.

  Authors: Nick Lane, John F Allen, William Martin

  BioEssays : news and reviews in molecular, cellular and developmental biology. 04/2010; 32(4):271-80.

  Despite thermodynamic, bioenergetic and phylogenetic failings, the 81-year-old concept of primordial soup remains central to mainstream thinking on the origin of life. But soup is homogeneous in pHDespite thermodynamic, bioenergetic and phylogenetic failings, the 81-year-old concept of primordial soup remains central to mainstream thinking on the origin of life. But soup is homogeneous in pH and redox potential, and so has no capacity for energy coupling by chemiosmosis. Thermodynamic constraints make chemiosmosis strictly necessary for carbon and energy metabolism in all free-living chemotrophs, and presumably the first free-living cells too. Proton gradients form naturally at alkaline hydrothermal vents and are viewed as central to the origin of life. Here we consider how the earliest cells might have harnessed a geochemically created proton-motive force and then learned to make their own, a transition that was necessary for their escape from the vents. Synthesis of ATP by chemiosmosis today involves generation of an ion gradient by means of vectorial electron transfer from a donor to an acceptor. We argue that the first donor was hydrogen and the first acceptor CO2.

• BioEssays 4/2010.

  Authors: Nick Lane, John F Allen, William Martin

  BioEssays : news and reviews in molecular, cellular and developmental biology. 03/2010; 32(4).

• A unifying view of ageing and disease: the double-agent theory.

  Authors: Nick Lane

  Journal of theoretical biology. 01/2004; 225(4):531-40.

  The quest for therapies based on molecular genetics (pharmacogenomics, DNA microarrays, etc.) drives pharmaceutical research into individual diseases of old age, but has failed to deliver anThe quest for therapies based on molecular genetics (pharmacogenomics, DNA microarrays, etc.) drives pharmaceutical research into individual diseases of old age, but has failed to deliver an unequivocal clinical breakthrough. Attempts to treat most age-related diseases using antioxidant supplements have been equally disappointing, despite the clear benefits of a healthy diet. The double-agent theory is a new, unifying synthesis that draws on flaws in three leading theories of ageing. It argues that there is a tradeoff between oxidative stress as a critical redox signal that marshals genetic defences against physiological stress (such as infection) and oxidative stress as a cause of ageing and age-related disease. The stress response and ageing are linked by redox-sensitive transcription factors, such as NFkappaB. Ageing is a function of rising intracellular oxidative stress, rather than chronological time, but this relationship is obscured because free-radical leakage from mitochondria also tends to rise with age. Mitochondrial leakage produces a genetic response which mirrors that following infection, but because mitochondrial leakage is continuous the shift in gene expression is persistent, leading to the chronic inflammation characteristic of old age. Age-related diseases are thus the price we pay for redox control of stress-gene expression. Because the selective pressure favouring the stress response in youth is stronger than that penalising degenerative diseases after reproductive decline, we may be homeostatically refractory to antioxidant supplements that 'swamp' the redox switch. Furthermore, because genetic selection takes place predominantly in the reductive homeostatic environment of youth, alleles associated with age-related diseases are not inherently damaging (they do not inevitably express a negative effect over time), but are simply less effective in the oxidising conditions of old age. Gene therapies for age-related diseases are unlikely to succeed unless oxidative stress can be controlled physiologically, thereby altering the activity and function of potentially hundreds of genes.

• New light on medicine.

  Authors: Nick Lane

  Scientific American. 02/2003; 288(1):38-45.

• Hypothermic renal preservation with a sucrose/ polyethylene glycol solution in a rabbit renal transplant model.

  Authors: Barry J Fuller, Colin Shurey, Nick Lane, Alex Petrenko, Colin Green

  Cryo letters. 27(2):127-32.

  Renal preservation at for 24 hours at hypothermia was studied in a rabbit model after flush cooling with sucrose-based solution (SBS), compared with a standard preservation solution (in this case,Renal preservation at for 24 hours at hypothermia was studied in a rabbit model after flush cooling with sucrose-based solution (SBS), compared with a standard preservation solution (in this case, Marshall's Hypertonic Citrate solution - HCA). Polyethylene glycol supplementation to SBS (SBS-PEG) was also investigated. Renal function was measured by plasma creatinine assays during 1 months post transplantation, and pathology of the explanted kidneys was undertaken. Results showed that survival at 28 days was similar in all groups, (HCA - 3 out of 6; SBS - 2 out of 5; SBS-PEG - 3 out of 5), and there were no differences in recovery of plasma creatinine values. Histopathological evaluation of the grafts indicated that SBS preservation resulted in more severe damage after transplantation (P less than 0.05 in both corticomedullary region and medulla compared to HCA), whilst addition of PEG reduced the damage score to that seen with HCA. SBS can be used as a simple, inexpensive preservation solution for kidney cold storage provided that PEG is used as an additional colloid.