Have a personal or library account? Click to login

The Maximum Genetic Diversity Theory: A Comprehensive Framework for Understanding Evolutionary Processes

By:
Open Access
|Apr 2025

References

  1. Lamarck JB. Zoological philosophy: an exposition with regard to the natural history of animals. Chicago: University of Chicago Press; 1984.
  2. Lewontin R. What is evolutionary theory. 2003. Santa Fe Institute. Available from: https://www.youtube.com/watch?v=n6W_FzjaKlw. (Accessed date: November 11, 2003)
  3. Newman S. Remembering Richard Lewontin. Biopolitical Times, Center for Genetics and Society; 2021. Available from: https://www.geneticsandsociety.org/biopolitical-times/remembering-richard-lewontin-1929-2021. (Accessed date: July 6, 2001)
  4. Simpson GG. Tempo and mode in evolution. New York: Columbia University Press; 1944.
  5. Bickel D. Testing hypotheses of molecular evolution. Phylogenetic trees and molecular evolution. Springer briefs in systems biology. Cham: Springer; 2022. p. 71–77.
  6. 黄石 and 朱作斌, 系统生物学与进化理论. 系统生物学, ed. 朱作斌, 张潇, and 王亮. 2022, 南京: 东南大学出版社.
  7. Zuckerkandl E, Pauling L. Molecular disease, evolution, and genetic heterogeneity. In: Kasha M, Pullman B. (eds.) Horizons in biochemistry. New York: Academic Press; 1962. p.189–225.
  8. Margoliash E. Primary structure and evolution of cytochrome C. Proceedings of the National academy of Sciences of the United States of America. 1963;50: 672–679. doi: 10.1073/pnas.50.4.672
  9. Doolittle RF, Blombaeck B. Amino-acid sequence investigations of fibrinopeptides from various mammals: evolutionary implications. Nature. 1964;202: 147–152. doi: 10.1038/202147a0
  10. Kumar S. Molecular clocks: four decades of evolution. Nature Reviews Genetics. 2005;6(8): 654–662. doi: 10.1038/nrg1659
  11. Luo D, Huang S. The genetic equidistance phenomenon at the proteomic level. Genomics. 2016;108(1): 25–30. doi: 10.1016/j.ygeno.2016.03.002
  12. Yuan D, Huang S. Genetic equidistance at nucleotide level. Genomics. 2017;109: 192–195. doi: 10.1016/j.ygeno.2017.03.002
  13. Copley RR, Schultz J, Ponting CP, Bork P. Protein families in multicellular organisms. Current Opinion in Structural Biology. 1999;9: 408–415. doi: 10.1016/S0959-440X(99)80055-4
  14. Denton M. Evolution: a theory in crisis. Chevy Chase, MD: Adler & Adler; 1985.
  15. Bergeron LA, Besenbacher S, Zheng J, Li P, Bertelsen MF, Quintard B, et al. Evolution of the germline mutation rate across vertebrates. Nature. 2023;615(7951): 285–291. doi: 10.1038/s41586-023-05752-y
  16. Brownstein CD, MacGuigan DJ, Kim D, Orr O, Yang L, David SR, et al. The genomic signatures of evolutionary stasis. Evolution; International Journal of Organic Evolution. 2024;78(5): 821–834. doi: 10.1093/evolut/qpae028
  17. Mello B, Schrago CG. Modeling substitution rate evolution across lineages and relaxing the molecular clock. Genome Biology and Evolution. 2024;16(9): evae199. doi: 10.1093/gbe/evae199
  18. Drummond AJ, Ho SY, Phillips MJ, Rambaut A. Relaxed phylogenetics and dating with confidence. PLoS Biology. 2006;4(5): e88. doi: 10.1371/journal.pbio.0040088
  19. Van Valen L. Molecular evolution as predicted by natural selection. Journal of Molecular Evolution. 1974;3: 89–101. doi: 10.1007/BF01796554
  20. Clarke B. Darwinian evolution of proteins. Science. 1970;168(934): 1009–1011. doi: 10.1126/science.168.3934.1009
  21. Richmond RC. Non-Darwinian evolution: a critique. Nature. 1970;225(5237): 1025–1028. doi: 10.1038/2251025a0
  22. Kimura M. Evolutionary rate at the molecular level. Nature. 1968;217(5129): 624–626. doi: 10.1038/217624a0
  23. Kimura M, Ohta T. On the rate of molecular evolution. Journal of Molecular Evolution. 1971;1: 1–17. doi: 10.1007/BF01659390
  24. King JL, Jukes TH. Non-Darwinian evolution. Science. 1969;164: 788–798. doi: 10.1126/science.164.3881.788
  25. Ayala FJ. Molecular clock mirages. Bioessays: News and Reviews in Molecular, Cellular and Developmental Biology. 1999;21(1): 71–75. doi: 10.1002/(SICI)1521-1878(199901)21:1<;71::AID-BIES9>3.0.CO;2-B
  26. Pulquerio MJ, Nichols RA. Dates from the molecular clock: how wrong can we be? Trends in Ecology & Evolution. 2007;22(4): 180–184. doi: 10.1016/j.tree.2006.11.013
  27. Kimura M, Ohta T. Protein polymorphism as a phase of molecular evolution. Nature. 1971;229: 467–479. doi: 10.1038/229467a0
  28. Kimura M. The neutral theory of molecular evolution. Cambridge: Cambridge University Press; 1983.
  29. Leigh EG Jr. Neutral theory: a historical perspective. Journal of Evolutionary Biology. 2007;20(6): 2075–2091. doi: 10.1111/j.1420-9101.2007.01410.x
  30. Fisher RA. The genetical theory of natural selection. Oxford, UK: Oxford University Press; 1930.
  31. Wright S. The roles of mutation, inbreeding, crossbreeding and selection in evolution. Proceedings of the Sixth International Congress of Genetics. 1932;1: 356–366.
  32. Haldane JBS. The cost of natural selection. Journal of Genetics. 1957;55: 511–524. doi: 10.1007/BF02984069
  33. Sueoka N. On the genetic basis of variation and heterogeneity of DNA base composition. Proceedings of the National academy of Sciences of the United States of America. 1962;48: 582–592. doi: 10.1073/pnas.48.4.582
  34. Freese E. On the evolution of the base composition of DNA. Journal of Theoretical Biology. 1962;3(1): 82–101. doi: 10.1016/S0022-5193(62)80005-8
  35. Lewontin RC. The genetic basis of evolutionary change. New York and London: Columbia University Press; 1974.
  36. Lewontin RC, Hubby JL. A molecular approach to the study of genic heterozygosity in natural populations. II. Amount of variation and degree of heterozygosity in natural populations of Drosophila pseudoobscura. Genetics. 1966;54(2): 595–609. doi: 10.1093/genetics/54.2.595
  37. Dietrich MR. The origins of the neutral theory of molecular evolution. Journal of the History of Biology. 1994;27(1): 21–59. doi: 10.1007/BF01058626
  38. Suarez E, Barahona A. The experimental roots of the neutral theory of molecular evolution. History and Philosophy of the Life Sciences. 1996;18: 55–81.
  39. Palazzo AF, Gregory TR. The case for junk DNA. Plos Genetics. 2014;10(5): e1004351. doi: 10.1371/journal.pgen.1004351
  40. Rands CM, Meader S, Ponting CP, Lunter G. 8.2% of the Human genome is constrained: variation in rates of turnover across functional element classes in the human lineage. Plos Genetics. 2014;10(7): e1004525. doi: 10.1371/journal.pgen.1004525
  41. Doolittle WF, Brunet TDP. On causal roles and selected effects: our genome is mostly junk. BMC Biology. 2017;15(1): 116. doi: 10.1186/s12915-017-0460-9
  42. Kimura M, Crow JF. The number of alleles that can be maintained in a finite population. Genetics. 1964;49: 725–738. doi: 10.1093/genetics/49.4.725
  43. Demeulemeester J, Dentro SC, Gerstung M, Van Loo P. Biallelic mutations in cancer genomes reveal local mutational determinants. Nature Genetics. 2022;54(2): 128–133. doi: 10.1038/s41588-021-01005-8
  44. Harpak A, Bhaskar A, Pritchard JK. Mutation rate variation is a primary determinant of the distribution of allele frequencies in humans. Plos Genetics. 2016;12(12): e1006489. doi: 10.1371/journal.pgen.1006489
  45. Porubsky D, Dashnow H, Sasani TA, Logsdon GA, Hallast P, Noyes MD, et al. A familial, telomere-to-telomere reference for human de novo mutation and recombination from a four-generation pedigree. bioRxiv. 2024: 2024.08.05.606142. doi: 10.1101/2024.08.05.606142
  46. Lynch M, Wei W, Ye Z, Pfrender M. The genome-wide signature of short-term temporal selection. Proceedings of the National academy of Sciences of the United States of America. 2024;121(28): e2307107121. doi: 10.1073/pnas.2307107121
  47. Yuan D, Zhu Z, Tan X, Liang J, Zeng C, Zhang J, et al. Scoring the collective effects of SNPs: association of minor alleles with complex traits in model organisms. Science China Life Sciences. 2014;57(9): 876–888. doi: 10.1007/s11427-014-4704-4
  48. Zhu Z, Yuan D, Luo D, Lu X, Huang S. Enrichment of minor alleles of common SNPs and improved risk prediction for Parkinson's disease. Plos One. 2015;10(7): e0133421. doi: 10.1371/journal.pone.0133421
  49. Zhu Z, Man X, Xia M, Huang Y, Yuan D, Huang S. Collective effects of SNPs on transgenerational inheritance in Caenorhabditis elegans and budding yeast. Genomics. 2015;106(1): 23–29. doi: 10.1016/j.ygeno.2015.04.002
  50. Yuan D, Zhu Z, Tan X, Liang J, Zeng C, Zhang J, et al. Minor alleles of common SNPs quantitatively affect traits/diseases and are under both positive and negative selection. arXiv. 2012;1209.2911. doi: 10.1007/s11427-014-4704-4
  51. Zhu Z, Lu Q, Wang J, Huang S. Collective effects of common SNPs in foraging decisions in Caenorhabditis elegans and an integrative method of identification of candidate genes. Scientific Reports. 2015;5: 16904. doi: 10.1038/srep16904
  52. Kimura M, Ohta T. On some principles governing molecular evolution. Proceedings of the National academy of Sciences of the United States of America. 1974;71(7): 2848–2852. doi: 10.1073/pnas.71.7.2848
  53. Quinodoz SA, Jachowicz JW, Bhat P, Ollikainen N, Banerjee AK, Goronzy IN, et al. RNA promotes the formation of spatial compartments in the nucleus. Cell. 2021;184(23): 5775–5790.e30. doi: 10.1016/j.cell.2021.10.014
  54. Basu A, Bobrovnikov DG, Cieza B, Arcon JP, Qureshi Z, Orozco M, et al. Deciphering the mechanical code of the genome and epigenome. Nature Structural & Molecular Biology. 2022;29(12): 1178–1187. doi: 10.1038/s41594-022-00877-6
  55. Duttke SH, Guzman C, Chang M, Delos Santos NP, McDonald BR, Xie J, et al. Position-dependent function of human sequence-specific transcription factors. Nature. 2024;631(8022): 891–898. doi: 10.1038/s41586-024-07662-z
  56. Eder M, Moene CJI, Dauban L, Leemans C, Steensel BV. Functional maps of a genomic locus reveal confinement of an Enhancer by its target gene. bioRxiv. 2024. doi: 10.1101/2024.08.26.609360
  57. Du AY, Chobirko JD, Zhuo X, Feschotte C, Wang T. Regulatory transposable elements in the encyclopedia of DNA elements. Nature Communications. 2024;15(1): 7594. doi: 10.1038/s41467-024-51921-6
  58. Kimura M. Genetic variability maintained in a finite population due to mutational production of neutral and nearly neutral isoalleles. Genetical Research. 1968;11(3): 247–269. doi: 10.1017/S0016672300011459
  59. Shen X, Song S, Li C, Zhang J. Synonymous mutations in representative yeast genes are mostly strongly non-neutral. Nature. 2022;606(7915): 725–731. doi: 10.1038/s41586-022-04823-w
  60. Lu J, Wu CI. Weak selection revealed by the whole-genome comparison of the X chromosome and autosomes of human and chimpanzee. Proceedings of the National academy of Sciences of the United States of America. 2005;102(11): 4063–4067. doi: 10.1073/pnas.0500436102
  61. Nyerges A, Chiappino-Pepe A, Budnik B, Baas-Thomas M, Flynn R, Yan S, et al. Synthetic genomes unveil the effects of synonymous recoding. bioRxiv. 2024: 2024.06.16.599206. doi: 10.1101/2024.06.16.599206
  62. Rodriguez A, Diehl JD, Wright GS, Bonar CD, Lundgren TJ, Moss MJ, et al. Synonymous codon substitutions modulate transcription and translation of a divergent upstream gene by modulating antisense RNA production. Proceedings of the National academy of Sciences of the United States of America. 2024;121(36): e2405510121. doi: 10.1073/pnas.2405510121
  63. Leffler EM, Bullaughey K, Matute DR, Meyer WK, Ségurel L, Venkat A, et al. Revisiting an old riddle: what determines genetic diversity levels within species? Plos Biology. 2012;10(9): e1001388. doi: 10.1371/journal.pbio.1001388
  64. Buffalo V. Quantifying the relationship between genetic diversity and population size suggests natural selection cannot explain Lewontin's paradox. eLife. 2021;10: e67509. doi: 10.7554/eLife.67509
  65. Kern AD, Hahn MW. The neutral theory in light of natural selection. Molecular Biology and Evolution. 2018;35(6): 1366–1371. doi: 10.1093/molbev/msy092
  66. Kreitman M. The neutral theory is dead. Long live the neutral theory. Bioessays: News and Reviews in Molecular, Cellular and Developmental Biology. 1996;18(8): 678–683. discussion 683. doi: 10.1002/bies.950180812
  67. Cann RL, Stoneking AC, Wilson AC. Mitochondrial DNA and human evolution. Nature. 1987;325: 31–36. doi: 10.1038/325031a0
  68. Felsenstein J. Confidence limits on phylogenies: an approach using the bootstrap. Evolution; International Journal of Organic Evolution. 1985;39(4): 783–791. doi: 10.2307/2408678
  69. Huang S. The genetic equidistance result of molecular evolution is independent of mutation rates. Journal of Computer Science and Systems Biology. 2008;1: 092–102. doi: 10.4172/jcsb.1000009
  70. Avise JC. Molecular markers, natural history and evolution. New York, NY: Springer; 1994.
  71. Nei M, Kumar S. Molecular evolution and phylogenetics. New York: Oxford University Press; 2000.
  72. Ohta T. Slightly deleterious mutant substitutions in evolution. Nature. 1973;246(5428): 96–98. doi: 10.1038/246096a0
  73. Huang S. Histone methyltransferases, diet nutrients, and tumor suppressors. Nature Reviews Cancer. 2002;2: 469–476. doi: 10.1038/nrc819
  74. Huang S. Histone methylation and the initiation of cancer. In: Tollefsbol T. (ed.) Cancer epigenetics. New York: CRC Press; 2008. p. 109–158.
  75. Huang S. Inverse relationship between genetic diversity and epigenetic complexity. Nature Precedings. 2009. doi: 10.1038/npre.2009.1751.2
  76. Huang S. The overlap feature of the genetic equidistance result, a fundamental biological phenomenon overlooked for nearly half of a century. Biological Theory. 2010;5: 40–52. doi: 10.1162/BIOT_a_00021
  77. Santoni G, Astori S, Leleu M, Glauser L, Zamora SA, Schioppa M, et al. Chromatin plasticity predetermines neuronal eligibility for memory trace formation. Science. 2024;385(6707): eadg9982. doi: 10.1126/science.adg9982
  78. Aquadro CF. Why is the genome variable? Insights from Drosophila. Trends in Genetics. 1992;8(10): 355–362. doi: 10.1016/0168-9525(92)90281-8
  79. Lewontin RC. Twenty-five years ago in genetics: electrophoresis in the development of evolutionary genetics: milestone or millstone? Genetics. 1991;128(4): 657–662. doi: 10.1093/genetics/128.4.657
  80. Bateson W. Materials for the study of variation treated with especial regard to discontinuity in the origin of species. London: Macmillan; 1894.
  81. Nei M, Li WH. Mathematical model for studying genetic variation in terms of restriction endonucleases. Proceedings of the National Academy of Sciences of the United States of America. 1979;76: 5269–5273. doi: 10.1073/pnas.76.10.5269
  82. Steux C, Szpiech ZA. The maintenance of deleterious variation in wild Chinese rhesus macaques. Genome Biology and Evolution. 2024;16(6): evae115. doi: 10.1093/gbe/evae115
  83. Ellegren H, Galtier N. Determinants of genetic diversity. Nature Reviews Genetics. 2016;17(7): 422–433. doi: 10.1038/nrg.2016.58
  84. Nevo E. Genetic diversity. In: Levin SA. (ed.) Encyclopedia of biodiversity. Amsterdam: Elsevier Inc; 2001. p. 662–677. doi: 10.1016/B978-0-12-384719-5.00065-4
  85. Yang J, Lusk R, Li WH. Organismal complexity, protein complexity, and gene duplicability. Proceedings of the National academy of Sciences of the United States of America. 2003;100(26): 15661–15665. doi: 10.1073/pnas.2536672100
  86. Levine M, Tjian R. Transcription regulation and animal diversity. Nature. 2003;424(6945): 147–151. doi: 10.1038/nature01763
  87. Vinogradov AE, Anatskaya OV. Organismal complexity, cell differentiation and gene expression: human over mouse. Nucleic Acids Research. 2007;35(19): 6350–6356. doi: 10.1093/nar/gkm723
  88. Bonner JT. Perspective: the size-complexity rule. Evolution; International Journal of Organic Evolution. 2004;58: 1883–1890. doi: 10.1111/j.0014-3820.2004.tb00476.x
  89. Carroll SB. Chance and necessity: the evolution of morphological complexity and diversity. Nature. 2001;409(6823): 1102–1109. doi: 10.1038/35059227
  90. McShea DW. Metazoan complexity and evolution: is there a trend? Evolution; International Journal of Organic Evolution. 1996;50: 477–492. doi: 10.2307/2410824
  91. Bonner JT. The evolution of complexity. Princeton, NJ: Princeton University Press; 1988.
  92. Vogel C, Chothia C. Protein family expansions and biological complexity. PLoS Computational Biology. 2006;2(5): e48. doi: 10.1371/journal.pcbi.0020048
  93. Remy JJ. Stable inheritance of an acquired behavior in Caenorhabditis elegans. Current Biology: CB. 2010;20(20): R877–R878. doi: 10.1016/j.cub.2010.08.013
  94. Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005;308(5727): 1466–1469. doi: 10.1126/science.1108190
  95. Hitchins MP, Wong JJ, Suthers G, Suter CM, Martin DI, Hawkins NJ, et al. Inheritance of a cancer-associated MLH1 germ-line epimutation. New England Journal of Medicine. 2007;356(7): 697–705. doi: 10.1056/NEJMoa064522
  96. Cropley JE, Suter CM, Beckman KB, Martin DI. Germ-line epigenetic modification of the murine A vy allele by nutritional supplementation. Proceedings of the National academy of Sciences of the United States of America. 2006;103(46): 17308–17312. doi: 10.1073/pnas.0607090103
  97. Huypens P, Sass S, Wu M, Dyckhoff D, Tschöp M, Theis F, et al. Epigenetic germline inheritance of diet-induced obesity and insulin resistance. Nature Genetics. 2016;48(5): 497–499. doi: 10.1038/ng.3527
  98. Fitz-James MH, Cavalli G. Molecular mechanisms of transgenerational epigenetic inheritance. Nature Reviews Genetics. 2022;23(6): 325–341. doi: 10.1038/s41576-021-00438-5
  99. Yu J, Zhang Y, Fang Y, Paulo JA, Yaghoubi D, Hua X, et al. A replisome-associated histone H3-H4 chaperone required for epigenetic inheritance. Cell. 2024;187: 5010.e–5028.e. doi: 10.1016/j.cell.2024.07.006
  100. Hu T, Long M, Yuan D, Zhu Z, Huang Y, Huang S. The genetic equidistance result, misreading by the molecular clock and neutral theory and reinterpretation nearly half of a century later. Science China Life Sciences. 2013;56: 254–261. doi: 10.1007/s11427-013-4452-x
  101. Huang S. New thoughts on an old riddle: what determines genetic diversity within and between species? Genomics. 2016;108(1): 3–10. doi: 10.1016/j.ygeno.2016.01.008
  102. Huang S. The maximum genetic diversity theory of molecular evolution. Communications in Information and Systems. 2023;23: 359–392. doi: 10.4310/CIS.2023.v23.n4.a1
  103. Zhu Z, Han C, Huang S. New insights shed light on the enigma of genetic diversity and species complexity. Science China Life Sciences. 2024;67: 2774–2776. doi: 10.1007/s11427-023-2610-2
  104. Orr HA. Adaptation and the cost of complexity. Evolution; International Journal of Organic Evolution. 2000;54(1): 13–20. doi: 10.1111/j.0014-3820.2000.tb00002.x
  105. Parts L, Batté A, Lopes M, Yuen MW, Laver M, San Luis BJ, et al. Natural variants suppress mutations in hundreds of essential genes. Molecular Systems Biology. 2021;17(5): e10138. doi: 10.15252/msb.202010138
  106. Gould SJ, Eldredge N. Punctuated equilibrium comes of age. Nature. 1993;366(6452): 223–227. doi: 10.1038/366223a0
  107. Rudman SM, Greenblum SI, Rajpurohit S, Betancourt NJ, Hanna J, Tilk S, et al. Direct observation of adaptive tracking on ecological time scales in Drosophila. Science. 2022;375(6586): eabj7484. doi: 10.1126/science.abj7484
  108. Shoval O, Sheftel H, Shinar G, Hart Y, Ramote O, Mayo A, et al. Evolutionary trade-offs, Pareto optimality, and the geometry of phenotype space. Science. 2012;336(6085): 1157–1160. doi: 10.1126/science.1217405
  109. Wang M, Wang D, Yu J, Huang S. Enrichment in conservative amino acid changes among fixed and standing missense variations in slowly evolving proteins. PeerJ. 2020;8: e9983. doi: 10.7717/peerj.9983
  110. Bergsten J. A review of long-branch attraction. Cladistics: the International Journal of the Willi Hennig Society. 2005;21: 163–193. doi: 10.1111/j.1096-0031.2005.00059.x
  111. Huang S. Primate phylogeny: molecular evidence for a pongid clade excluding humans and a prosimian clade containing tarsiers. Science China Life Sciences. 2012;55: 709–725. doi: 10.1007/s11427-012-4350-7
  112. Bickel D. A generalization of null hypothesis significance testing with applications to replication failures, molecular evolution models, and bounded parameter spaces. Zenodo. 2021. doi: 10.5281/zenodo.5123388
  113. Chen Z, Baeza JA, Chen C, Gonzalez MT, González VL, Greve C, et al. A genome-based phylogeny for Mollusca is concordant with fossils and morphology. Science. 2025;387(6737): 1001–1007. doi: 10.1126/science.ads0215
  114. Mao Y, Harvey WT, Porubsky D, Munson KM, Hoekzema K, Lewis AP, et al. Structurally divergent and recurrently mutated regions of primate genomes. Cell. 2024;187(6): 1547–1562.e13. doi: 10.1016/j.cell.2024.01.052
  115. Gao H, Hamp T, Ede J, Schraiber JG, McRae J, Singer-Berk M, et al. The landscape of tolerated genetic variation in humans and primates. Science (New York, N.Y.). 2023;380(6648): eabn8153. doi: 10.1126/science.abn8197
  116. Rhesus Macaque Genome Sequencing and Analysis Consortium, Gibbs RA, Rogers J, Katze MG, Bumgarner R, Weinstock GM, et al. Evolutionary and biomedical insights from the rhesus macaque genome. Science (New York, N.Y.). 2007;316(5822): 222–234. doi: 10.1126/science.1139247
  117. Kuiken C, Korber B, Shafer RW. HIV sequence databases. AIDS Reviews. 2003;5(1): 52–61.
  118. Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature. 2005;437(7055): 69–87. doi: 10.1038/nature04072
  119. Zhang S, Xu N, Fu L, Yang X, Li Y, Yang Z, et al. Comparative genomics of macaques and integrated insights into genetic variation and population history. bioRxiv. 2024: 2024.04.07.588379. doi: 10.1101/2024.04.07.588379
  120. Orkin JD, Kuderna LFK, Hermosilla-Albala N, Fontsere C, Aylward ML, Janiak MC, et al. Ecological and anthropogenic effects on the genomic diversity of lemurs in Madagascar. Nature Ecology and Evolution. 2025;9(1): 42–56. doi: 10.1038/s41559-024-02596-1
  121. Oberstaller J, Xu S, Naskar D, Zhang M, Wang C, Gibbons J, et al. Supersaturation mutagenesis reveals adaptive rewiring of essential genes among malaria parasites. Science. 2025;387(6734): eadq7347. doi: 10.1126/science.adq7347
  122. Camellato BR, Brosh R, Ashe HJ, Maurano MT, Boeke JD. Synthetic reversed sequences reveal default genomic states. Nature. 2024;628(8007): 373–380. doi: 10.1038/s41586-024-07128-2
  123. Wang M, Huang S. The collective effects of genetic variants and complex traits. Journal of Human Genetics. 2023;68: 255–262. doi: 10.1038/s10038-022-01105-1
  124. Chen CY, Tian R, Ge T, Lam M, Sanchez-Andrade G, Singh T, et al. The impact of rare protein coding genetic variation on adult cognitive function. Nature Genetics. 2023;55(6): 927–938. doi: 10.1038/s41588-023-01398-8
  125. Ganna A, Genovese G, Howrigan DP, Byrnes A, Kurki M, Zekavat SM, et al. Ultra-rare disruptive and damaging mutations influence educational attainment in the general population. Nature Neuroscience. 2016;19(12): 1563–1565. doi: 10.1038/nn.4404
  126. Ganna A, Satterstrom FK, Zekavat SM, Das I, Kurki MI, Churchhouse C, et al. Quantifying the impact of rare and ultra-rare coding variation across the phenotypic spectrum. American Journal of Human Genetics. 2018;102(6): 1204–1211. doi: 10.1016/j.ajhg.2018.05.002
  127. Sha Z, Sun KY, Jung B, Barzilay R, Moore TM, Almasy L, et al. The copy number variant architecture of psy-chopathology and cognitive development in the ABCD® study. medRxiv. 2024: 2024.05.14.24307376. doi: 10.1101/2024.05.14.24307376
  128. Wainberg M, Forde NJ, Mansour S, Kerrebijn I, Medland SE, Hawco C, et al. Genetic architecture of the structural connectome. Nature Communications. 2024;15(1): 1962. doi: 10.1038/s41467-024-46023-2
  129. Zhang S, Xu N, Fu L, Yang X, Ma K, Li Y, et al. Integrated analysis of the complete sequence of a macaque genome. Nature. 2025. doi: 10.1038/s41586-025-08596-w
  130. Joly M, Micheletta J, De Marco A, Langermans JA, Sterck EHM, Waller BM. Comparing physical and social cognitive skills in macaque species with different degrees of social tolerance. Proceedings. Biological Sciences/the Royal Society. 2017;284(1862): 20162738. doi: 10.1098/rspb.2016.2738
  131. Kuderna LFK, Gao H, Janiak MC, Kuhlwilm M, Orkin JD, Bataillon T, et al. A global catalog of whole-genome diversity from 233 primate species. Science. 2023;380(6648): 906–913. doi: 10.1126/science.abn7829
  132. de Manuel M, Kuhlwilm M, Frandsen P, Sousa VC, Desai T, Prado-Martinez J, et al. Chimpanzee genomic diversity reveals ancient admixture with bonobos. Science. 2016;354(6311): 477–481. doi: 10.1126/science.aag2602
  133. Tishkoff SA, Reed FA, Friedlaender FR, Ehret C, Ranciaro A, Froment A, et al. The genetic structure and history of Africans and African Americans. Science. 2009;324(5930): 1035–1044. doi: 10.1126/science.1172257
  134. Lynn R. Race differences in intelligence. Augusta, GA: Washington Summit Publishers; 2006.
  135. Nédélec Y, Sanz J, Baharian G, Szpiech ZA, Pacis A, Dumaine A, et al. Genetic ancestry and natural selection drive population differences in immune responses to pathogens. Cell. 2016;167(3): 657–669.e21. doi: 10.1016/j.cell.2016.09.025
  136. Quach H, Rotival M, Pothlichet J, Loh YE, Dannemann M, Zidane N, et al. Genetic adaptation and neandertal admixture shaped the immune system of human populations. Cell. 2016;167(3): 643–656.e17. doi: 10.1016/j.cell.2016.09.024
  137. Lei X, Yuan D, Zhu Z, Huang S. Collective effects of common SNPs and risk prediction in lung cancer. Heredity. 2018;121: 537–547. doi: 10.1038/s41437-018-0063-4
  138. He P, Lei X, Yuan D, Zhu Z, Huang S. Accumulation of minor alleles and risk prediction in schizophrenia. Scientific Reports. 2017;7(1): 11661. doi: 10.1038/s41598-017-12104-0
  139. Sanjak JS, Sidorenko J, Robinson MR, Thornton KR, Visscher PM. Evidence of directional and stabilizing selection in contemporary humans. Proceedings of the National academy of Sciences of the United States of America. 2018;115(1): 151–156. doi: 10.1073/pnas.1707227114
  140. Amos W, Elhaik E. Unexpected D-tour ahead: why the D-statistic, applied to humans, measures mutation rate variation not Neanderthal introgression. bioRxiv. 2025. Available from: https://www.biorxiv.org/content/10.1101/2024.12.31.630954v2. doi: 10.1101/2024.12.31.630954 (Accessed date: December 31, 2024)
  141. Horton CA, Alexandari AM, Hayes MGB, Marklund E, Schaepe JM, Aditham AK, et al. Short tandem repeats bind transcription factors to tune eukaryotic gene expression. Science. 2023;381(6664): eadd1250. doi: 10.1126/science.add1250
  142. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489(7414): 57–74. doi: 10.1038/nature11247
  143. Mattick JS. A Kuhnian revolution in molecular biology: most genes in complex organisms express regulatory RNAs. Bioessays: News and Reviews in Molecular, Cellular and Developmental Biology. 2023;45(9): e2300080. doi: 10.1002/bies.202300080
  144. Meneu L, Chapard C, Serizay J, Westbrook A, Routhier E, Ruault M, et al. Sequence-dependent activity and compartmentalization of foreign DNA in a eukaryotic nucleus. Science. 2025;387(6734): eadm9466. doi: 10.1126/science.adm9466
  145. Li A, Evans DS, Cummings S, Ideker T. Somatic mutation as an explanation for epigenetic aging. Nature Aging. 2025. doi: 10.1038/s43587-024-00794-x
  146. Lake NJ, Ma K, Liu W, Battle SL, Laricchia KM, Tiao G, et al. Quantifying constraint in the human mitochondrial genome. Nature. 2024;635: 390–397. doi: 10.1038/s41586-024-08048-x
  147. Couce A, Limdi A, Magnan M, Owen SV, Herren CM, Lenski RE, et al. Changing fitness effects of mutations through long-term bacterial evolution. Science. 2024;383(6681): eadd1417. doi: 10.1126/science.add1417
  148. Halabi N, Rivoire O, Leibler S, Ranganathan R. Protein sectors: evolutionary units of three-dimensional structure. Cell. 2009;138(4): 774–786. doi: 10.1016/j.cell.2009.07.038
  149. Jeong H, Dishuck PC, Yoo D, Harvey WT, Munson KM, Lewis AP, et al. Structural polymorphism and diversity of human segmental duplications. Nature Genetics. 2025;57(2): 390–401. doi: 10.1038/s41588-024-02051-8
  150. Simpson KJ, Mian S, Forrestel EJ, Hackel J, Morton JA, Leitch AR, et al. Bigger genomes provide environment-dependent growth benefits in grasses. The New Phytologist. 2024;244(5): 2049–2061. doi: 10.1111/nph.20150
  151. Moore L, Cagan A, Coorens THH, Neville MDC, Sanghvi R, Sanders MA, et al. The mutational landscape of human somatic and germline cells. Nature. 2021;597(7876): 381–386. doi: 10.1038/s41586-021-03822-7
  152. Ru Y, Deng X, Chen J, Zhang L, Xu Z, Lv Q, et al. Maternal age enhances purifying selection on pathogenic mutations in complex I genes of mammalian mtDNA. Nature Aging. 2024;4(9): 1211–1230. doi: 10.1038/s43587-024-00672-6
  153. Zeller E, Timmermann A, Yun KS, Raia P, Stein K, Ruan J. Human adaptation to diverse biomes over the past 3 million years. Science. 2023;380(6645): 604–608. doi: 10.1126/science.abq1288
  154. Exposito-Alonso M, Booker TR, Czech L, Gillespie L, Hateley S, Kyriazis CC, et al. Genetic diversity loss in the Anthropocene. Science. 2022;377(6613): 1431–1435. doi: 10.1126/science.abn5642
  155. Gross N, Maestre FT, Liancourt P, Berdugo M, Martin R, Gozalo B, et al. Unforeseen plant phenotypic diversity in a dry and grazed world. Nature. 2024;632(8026): 808–814. doi: 10.1038/s41586-024-07731-3
  156. Jenkin F. The origin of species. The North British Review. 1867;46: 277–318.
  157. Goldschmidt R. The material basis of evolution. New Haven, CT: Yale University Press; 1940.
  158. Forsdyke DR. Evolutionary bioinformatics. New York: Springer; 2011.
  159. Heng HH. Genome chaos: rethinking genetics, evolution, and molecular medicine. Cambridge, MA, USA: Academic Press Elsevier; 2019.
  160. Zhang Y. The genetic equidistance and maximum genetic diversity hypothesis: smoke and mirrors? bioRxiv. 2023. doi: 10.1101/2023.02.14.528494
  161. Huang S. A rebuttal to Zhang's critique of the genetic equidistance phenomenon and maximum genetic diversity hypothesis. Zenodo. 2025. doi: 10.5281/zenodo.14927073
  162. Yuan D, Lei X, Gui Y, Zhu Z, Wang M, Zhang Y, et al. Modern human origins: multiregional evolution of autosomes and East Asia origin of Y and mtDNA. bioRxiv. 2017. doi: 10.1101/101410
  163. Huang S. Examining models of modern human origins through the analysis of 43 fully sequenced human Y chromosomes, Communications in Information and Systems, in press. bioRxiv. 2023. doi: 10.1101/2023.11.09.566475
Language: English
Page range: 41 - 61
Published on: Apr 24, 2025
Published by: The Israel Biocomplexity Center
In partnership with: Paradigm Publishing Services
Publication frequency: 1 times per year

© 2025 Shi Huang, published by The Israel Biocomplexity Center
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.