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Biological Theory

, Volume 13, Issue 1, pp 4–9 | Cite as

Dysfunction, Disease, and the Limits of Selection

  • Zachary ArdernEmail author
Thematic section article: function and malfunction

Abstract

Paul Griffiths and John Matthewson argue that selected effects play the key role in determining whether a state is pathological. In response, it is argued that a selected effects account faces a number of difficulties in light of modern genomic research. Firstly, a modern history approach to selection is problematic as a basis for assigning function to human traits in light of the small population sizes in the hominin lineage, which imply that selection has played a limited role in shaping these genomes in the evolutionarily recent past. Secondly, determining both the genetic basis of disease and selective histories of the various alleles involved may be experimentally intractable. Thirdly, the existence of “selected disorders” is well supported, and yet on the other hand many other common diseases may not reduce evolutionary fitness. In summary, the biological ends promoted by natural selection, as best modeled in recent research, do not adequately ground a concept of dysfunction that aligns well with the interests of human health.

Keywords

Disease Dysfunction Function Genomics Health Human evolution Selected effects 

References

  1. Alföldi J, Lindblad-Toh K (2013) Comparative genomics as a tool to understand evolution and disease. Genome Res 23:1063–1068. doi: 10.1101/gr.157503.113 CrossRefGoogle Scholar
  2. Biswas S, Akey JM (2006) Genomic insights into positive selection. Trends Genet 22:437–446. doi: 10.1016/j.tig.2006.06.005 CrossRefGoogle Scholar
  3. Boorse C (1977) Health as a theoretical concept. Philos Sci 44:542. doi: 10.1086/288768 CrossRefGoogle Scholar
  4. Boyko AR, Williamson SH, Indap AR et al (2008) Assessing the evolutionary impact of amino acid mutations in the human genome. PLoS Genet 4:e1000083. doi: 10.1371/journal.pgen.1000083 CrossRefGoogle Scholar
  5. Cooper GM, Shendure J (2011) Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data. Nat Rev Genet 12:628–640. doi: 10.1038/nrg3046 CrossRefGoogle Scholar
  6. Cummins R (1975) Functional analysis. J Philos 72:741–765. doi: 10.2307/2024640 CrossRefGoogle Scholar
  7. De Gobbi M (2006) A regulatory SNP causes a human genetic disease by creating a new transcriptional promoter. Science 312:1215–1217. doi: 10.1126/science.1126431 CrossRefGoogle Scholar
  8. Dudley JT, Kim Y, Liu L et al (2012) Human genomic disease variants: a neutral evolutionary explanation. Genome Res 22:1383–1394. doi: 10.1101/gr.133702.111 CrossRefGoogle Scholar
  9. Dunham I, Kundaje A, Aldred SF et al (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74. doi: 10.1038/nature11247 CrossRefGoogle Scholar
  10. Galtier N (2016) Adaptive protein evolution in animals and the effective population size hypothesis. PLOS Genet 12:e1005774. doi: 10.1371/journal.pgen.1005774 CrossRefGoogle Scholar
  11. Garrigan D, Kingan SB, Pilkington MM et al (2007) Inferring human population sizes, divergence times and rates of gene flow from mitochondrial, X and Y chromosome resequencing data. Genetics 177:2195–2207. doi: 10.1534/genetics.107.077495 CrossRefGoogle Scholar
  12. Gazave E, Ma L, Chang D et al (2014) Neutral genomic regions refine models of recent rapid human population growth. Proc Natl Acad Sci USA 111:757–762. doi: 10.1073/pnas.1310398110 CrossRefGoogle Scholar
  13. Gluckman PD, Hanson MA (2008) Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective. Int J Obes 32:S62–S71. doi: 10.1038/ijo.2008.240 CrossRefGoogle Scholar
  14. Godfrey-Smith P (1994) A modern history theory of functions. Noûs 28:344. doi: 10.2307/2216063 CrossRefGoogle Scholar
  15. Graur D (2017) An upper limit on the functional fraction of the human genome. Genome Biol Evol 9:1880–1885. doi: 10.1093/gbe/evx121 CrossRefGoogle Scholar
  16. Graur D, Zheng Y, Price N et al (2013) On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of ENCODE. Genome Biol Evol 5:578–590. doi: 10.1093/gbe/evt028 CrossRefGoogle Scholar
  17. Griffiths PE, Matthewson J (2016) Evolution, dysfunction, and disease: a reappraisal: table 1. Br J Philos Sci. doi: 10.1093/bjps/axw021 Google Scholar
  18. Haerty W, Ponting CP (2013) Mutations within lncRNAs are effectively selected against in fruitfly but not in human. Genome Biol 14:R49. doi: 10.1186/gb-2013-14-5-r49 CrossRefGoogle Scholar
  19. Hangauer MJ, Vaughn IW, McManus MT (2013) Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs. PLoS Genet 9:e1003569. doi: 10.1371/journal.pgen.1003569 CrossRefGoogle Scholar
  20. Jensen JD (2014) On the unfounded enthusiasm for soft selective sweeps. Nat Commun 5:5281. doi: 10.1038/ncomms6281 CrossRefGoogle Scholar
  21. Karlsson EK, Kwiatkowski DP, Sabeti PC (2014) Natural selection and infectious disease in human populations. Nat Rev Genet 15:379–393. doi: 10.1038/nrg3734 CrossRefGoogle Scholar
  22. Khoury MJ, Janssens ACJW, Ransohoff DF (2013) How can polygenic inheritance be used in population screening for common diseases? Genet Med 15:437–443. doi: 10.1038/gim.2012.182 CrossRefGoogle Scholar
  23. Kingma E (2013) Naturalist accounts of mental disorder. Oxf Handb Online. doi: 10.1093/oxfordhb/9780199579563.013.0025 Google Scholar
  24. Kingma E (2017) Disease as scientific and as value-laden concept. In: Schramme T, Edwards S (eds) Handbook of the philosophy of medicine. Springer, Dordrecht, pp 45–63CrossRefGoogle Scholar
  25. Kirkwood TBL, Austad SN (2000) Why do we age? Nature 408:233–238. doi: 10.1038/35041682 CrossRefGoogle Scholar
  26. Koonin EV (2016) Splendor and misery of adaptation, or the importance of neutral null for understanding evolution. BMC Biol. doi: 10.1186/s12915-016-0338-2 Google Scholar
  27. Melé M, Javed A, Pybus M et al (2012) Recombination gives a new insight in the effective population size and the history of the old world human populations. Mol Biol Evol 29:25–30. doi: 10.1093/molbev/msr213 CrossRefGoogle Scholar
  28. Murray CJ, Richards MA, Newton JN et al (2013) UK health performance: findings of the Global Burden of Disease Study 2010. Lancet 381:997–1020. doi: 10.1016/S0140-6736(13)60355-4 CrossRefGoogle Scholar
  29. Pennisi E (2012) ENCODE project writes eulogy for junk DNA. Science 337:1159–1161. doi: 10.1126/science.337.6099.1159 CrossRefGoogle Scholar
  30. Smith MA, Gesell T, Stadler PF, Mattick JS (2013) Widespread purifying selection on RNA structure in mammals. Nucleic Acids Res 41:8220–8236. doi: 10.1093/nar/gkt596 CrossRefGoogle Scholar
  31. Wakefield JC (1992) The concept of mental disorder: on the boundary between biological facts and social values. Am Psychol 47(3):373–388. doi: 10.1037/0003-066X.47.3.373 CrossRefGoogle Scholar
  32. Wakefield JC (2015) Biological function and dysfunction: conceptual foundations of evolutionary psychopathology. The handbook of evolutionary psychology, vol 42, pp 1–19. doi: 10.1002/9781119125563.evpsych242
  33. Yu F, Lu J, Liu X et al (2015) Population genomic analysis of 962 whole genome sequences of humans reveals natural selection in non-coding regions. PLoS ONE 10:e0121644. doi: 10.1371/journal.pone.0121644 CrossRefGoogle Scholar

Copyright information

© Konrad Lorenz Institute for Evolution and Cognition Research 2017

Authors and Affiliations

  1. 1.Department of Microbiology and ZIEL Institute for Food & HealthTechnische Universität MünchenFreisingGermany

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