Autor: Sodré G. B. Neto
Afiliação: IPPTM – Instituto de Pesquisa em Paleogenética, TP53 e MicroRNA / CEGH / ICB / UFG
Resumo Estruturado
Introdução: A teoria da evolução biológica convencional fundamenta-se na premissa de que mutações aleatórias e seleção natural são capazes de gerar complexidade e viabilidade a longo prazo. No entanto, avanços na genética de populações e genômica comparativa sugerem um processo inverso: a degeneração sistemática do genoma pelo acúmulo de mutações deletérias, um fenômeno descrito como entropia genética [299].
Objetivo: Este artigo sintetiza evidências sobre o acúmulo de carga genética deletéria na linhagem humana e animal, propondo a ocorrência de um pico mutacional/radiativo recente durante o Holoceno, desencadeado por eventos catastróficos.
Métodos: Realizou-se uma revisão sistemática de literatura focada em taxas de mutação mitocondrial (mtDNA), acúmulo de mutações deletérias em populações pequenas e grandes, e o impacto de eventos catastróficos na geocronologia radioativa.
Resultados: As taxas de mutação observadas em estudos de linhagem (pedigree) são significativamente superiores às taxas filogenéticas tradicionais, indicando um erro sistemático na calibração do relógio molecular. Evidências geológicas sugerem que impactos de asteroides podem ter induzido picos de radiação via piezoeletricidade nuclear, acelerando o decaimento radioativo e as taxas mutacionais entre 5.000 e 10.000 anos atrás. A perda de funcionalidade em genes críticos, como o supressor tumoral p53, reflete essa senescência evolutiva.
Conclusão: A trajetória atual de acúmulo de mutações (deleteriome) aponta para um “mutational meltdown”, sugerindo que a viabilidade das espécies contemporâneas está severamente comprometida, com uma perspectiva de extinção iminente em termos geológicos.
Introdução
A narrativa evolutiva predominante postula que a vida na Terra se diversificou e se complexificou ao longo de bilhões de anos. Contudo, esta visão ignora um princípio fundamental da teoria da informação e da termodinâmica aplicado à biologia: a tendência natural ao desgaste e à perda de informação. A Teoria da Degeneração das Espécies (TDE) propõe que, longe de evoluir para formas mais complexas, os genomas estão em um estado de declínio progressivo devido ao acúmulo incessante de mutações deletérias.
O conceito de Entropia Genética, popularizado por John Sanford [299], argumenta que a grande maioria das mutações é “quase-neutra” e, portanto, invisível à seleção natural, acumulando-se silenciosamente em cada geração [8] [12] [259]. Este processo leva à degradação da aptidão biológica (fitness) e, eventualmente, ao colapso populacional [7] [13] [261]. Este artigo integra a TDE com evidências de um Pico Mutacional Holocênico, sugerindo que a história genética humana é muito mais curta e catastrófica do que o modelo uniformitarista sugere.
Métodos
A presente investigação baseia-se em uma meta-análise de dados genômicos e geocronológicos. Foram analisados:
1.Taxas de Mutação Mitocondrial: Comparação entre taxas baseadas em genealogia (pedigree) e taxas baseadas em calibrações fósseis [43] [45] [46] [47] [50] [52] [53] [56] [59] [60] [63] [65] [67] [68] [70] [71] [73] [74] [76] [77] [81].
2.Modelos de Acúmulo de Carga Genética: Avaliação do impacto de mutações deletérias na funcionalidade de proteínas essenciais [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [48] [49] [51] [54] [55] [57] [58] [61] [62] [64] [66] [69] [72] [75] [78] [79] [80] [162] [163] [164] [165] [166] [167] [168] [169] [170] [171] [172] [173] [174] [175] [176] [177] [178] [179] [180] [181] [182] [183] [184] [185] [186] [187] [188] [189] [190] [191] [192] [193] [194] [195] [196] [197] [198] [199] [200] [201] [202] [203] [204] [205] [206] [207] [208] [209] [210] [211] [212] [213] [214] [215] [216] [217] [218] [219] [220] [221] [222] [223] [224] [225] [226] [227] [228] [229] [230] [231] [232] [233] [234] [235] [236] [237] [238] [239] [240] [241] [242] [243] [244] [245] [246] [247] [248] [249] [250] [251] [252] [253] [254] [255] [256] [257] [258] [260] [261] [262] [263] [264] [265] [266] [267] [268] [269] [270] [271] [272] [273] [274] [275] [276] [277] [278] [279] [280] [281] [282] [283] [284] [285] [286] [287] [288] [289] [290] [291] [292] [293] [294] [295] [296] [297] [298].
3.Evidências de Catastrofismo: Revisão de marcadores geológicos de radiação intensa e impactos de asteroides sincronizados com picos de mutação observados em populações de mamíferos [122] [123] [124] [125] [126] [127] [128] [129] [130] [131] [132] [133] [134] [135] [136] [137] [138] [139] [140] [141] [142] [143] [144] [145] [146] [147] [148] [149] [150] [151] [152] [153] [154] [155] [156] [157] [158] [159] [160] [161] [300].
Resultados
O Pico Mutacional Holocênico
Estudos recentes sobre o DNA mitocondrial humano revelam uma discrepância alarmante [43] [45] [46] [47] [50] [52] [53] [56] [59] [60] [63] [65] [67] [68] [70] [71] [73] [74] [76] [77] [81]. Enquanto as taxas filogenéticas estimam a origem da “Eva Mitocondrial” em cerca de 150.000 a 200.000 anos, as taxas de mutação observadas diretamente em famílias (pedigree) sugerem uma cronologia de apenas 6.000 a 10.000 anos [45] [46] [63] [67] [68]. Esta divergência é explicada pela ocorrência de um evento de alta radiação no passado recente, que saturou os genomas com polimorfismos de nucleotídeo único (SNPs) [49] [51] [61] [62] [64] [66] [69] [72] [75] [78] [79] [80].
Catastrofismo Radioativo e Geocronologia
A validade da geocronologia uniformitarista é questionada pela evidência de decaimento radioativo acelerado [122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 300]. Propõe-se que impactos de grandes asteroides no Holoceno geraram pressões mecânicas extremas na crosta terrestre, resultando em fenômenos de piezoeletricidade nuclear. Tais eventos liberaram fluxos massivos de nêutrons e radiação gama, alterando as proporções isotópicas usadas em datações e induzindo picos mutacionais globais [300].
Senescência Evolutiva e o Deleteriome
A acumulação de mutações não é uniforme [1, 2, 3, 4, 5]. Genes vitais para a integridade genômica, como o p53 (guardião do genoma), mostram sinais de degradação funcional [82] [83] [84] [85] [86] [87] [88] [89] [90] [91] [92] [93] [94] [95] [96] [97] [98] [99] [100] [101] [102] [103] [104] [105] [106] [107] [108] [109] [110] [111] [112] [113] [114] [115] [116] [117] [118] [119] [120] [121]. O aumento exponencial de doenças degenerativas, câncer e diabetes nas últimas décadas é um reflexo direto dessa carga genética acumulada [202] [203] [204] [205] [206] [207] [208] [209] [210] [211] [212] [213] [214] [215] [216] [217] [218] [219] [220] [221] [222] [223] [224] [225] [226] [227] [228] [229] [230] [231] [232] [233] [234] [235] [236] [237] [238] [239] [240] [241] [242] [243] [244] [245] [246] [247] [248] [249] [250] [251] [252] [253] [254] [255] [256] [257] [258] [260] [261] [262] [263] [264] [265] [266] [267] [268] [269] [270] [271] [272] [273] [274] [275] [276] [277] [278] [279] [280] [281] [282] [283] [284] [285] [286] [287] [288] [289] [290] [291] [292] [293] [294] [295] [296] [297] [298], indicando que a humanidade está atingindo um ponto de saturação mutacional [7] [13] [261].
Discussão
A integração desses conceitos revela uma narrativa científica coerente: a vida iniciou-se com genomas de alta integridade que, após um evento catastrófico recente, entraram em um processo de decaimento acelerado [122] [123] [124] [125] [126] [127] [128] [129] [130] [131] [132] [133] [134] [135] [136] [137] [138] [139] [140] [141] [142] [143] [144] [145] [146] [147] [148] [149] [150] [151] [152] [153] [154] [155] [156] [157] [158] [159] [160] [161] [300]. A “seleção natural” atua apenas como um filtro para as mutações mais grosseiramente deletérias, mas é incapaz de deter o acúmulo de milhões de variantes levemente prejudiciais que comprometem a viabilidade sistêmica [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [48] [49] [51] [54] [55] [57] [58] [61] [62] [64] [66] [69] [72] [75] [78] [79] [80] [162] [163] [164] [165] [166] [167] [168] [169] [170] [171] [172] [173] [174] [175] [176] [177] [178] [179] [180] [181] [182] [183] [184] [185] [186] [187] [188] [189] [190] [191] [192] [193] [194] [195] [196] [197] [198] [199] [200] [201] [202] [203] [204] [205] [206] [207] [208] [209] [210] [211] [212] [213] [214] [215] [216] [217] [218] [219] [220] [221] [222] [223] [224] [225] [226] [227] [228] [229] [230] [231] [232] [233] [234] [235] [236] [237] [238] [239] [240] [241] [242] [243] [244] [245] [246] [247] [248] [249] [250] [251] [252] [253] [254] [255] [256] [257] [258] [260] [261] [262] [263] [264] [265] [266] [267] [268] [269] [270] [271] [272] [273] [274] [275] [276] [277] [278] [279] [280] [281] [282] [283] [284] [285] [286] [287] [288] [289] [290] [291] [292] [293] [294] [295] [296] [297] [298].
A invalidade da geocronologia uniformitarista é um ponto central [122] [123] [124] [125] [126] [127] [128] [129] [130] [131] [132] [133] [134] [135] [136] [137] [138] [139] [140] [141] [142] [143] [144] [145] [146] [147] [148] [149] [150] [151] [152] [153] [154] [155] [156] [157] [158] [159] [160] [161] [300]. Se as taxas de decaimento e mutação foram alteradas por eventos catastróficos, a escala de tempo da vida deve ser drasticamente reduzida [43] [45] [46] [47] [50] [52] [53] [56] [59] [60] [63] [65] [67] [68] [70] [71] [73] [74] [76] [77] [81]. Isso harmoniza a genética com o registro fóssil, onde vemos uma estase morfológica seguida de degeneração de tamanho e complexidade em muitas linhagens [122] [123] [124] [125] [126] [127] [128] [129] [130] [131] [132] [133] [134] [135] [136] [137] [138] [139] [140] [141] [142] [143] [144] [145] [146] [147] [148] [149] [150] [151] [152] [153] [154] [155] [156] [157] [158] [159] [160] [161] [300].
Conclusão
A Teoria da Degeneração Genética oferece um modelo robusto para explicar a trajetória biológica contemporânea [299]. O reconhecimento de um pico mutacional recente [45] [46] [63] [67] [68] e do acúmulo progressivo de mutações deletérias [6] [7] [8] [12] [13] [259] [261] é crucial para entender a vulnerabilidade das espécies à extinção [7] [13] [261]. A ciência deve considerar seriamente a possibilidade de que o “relógio biológico” da Terra esteja se aproximando de seu fim, exigindo uma reavaliação urgente dos paradigmas de conservação e evolução [202] [203] [204] [205] [206] [207] [208] [209] [210] [211] [212] [213] [214] [215] [216] [217] [218] [219] [220] [221] [222] [223] [224] [225] [226] [227] [228] [229] [230] [231] [232] [233] [234] [235] [236] [237] [238] [239] [240] [241] [242] [243] [244] [245] [246] [247] [248] [249] [250] [251] [252] [253] [254] [255] [256] [257] [258] [260] [261] [262] [263] [264] [265] [266] [267] [268] [269] [270] [271] [272] [273] [274] [275] [276] [277] [278] [279] [280] [281] [282] [283] [284] [285] [286] [287] [288] [289] [290] [291] [292] [293] [294] [295] [296] [297] [298].
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233.On the illusion of auxotrophy: met15Δ yeast cells can grow on inorganic sulfur, thanks to the previously uncharacterized homocysteine synthase Yll058w.. PMID: 36379252, PMC: PMC9763685. Link: https://pubmed.ncbi.nlm.nih.gov/36379252/
235.Multigenerational downregulation of insulin/IGF-1 signaling in adulthood improves lineage survival, reproduction, and fitness in Caenorhabditis elegans supporting the developmental theory of ageing.. PMID: 36199198, PMC: PMC10092551. Link: https://pubmed.ncbi.nlm.nih.gov/36199198/
236.A quantification method of somatic mutations in normal tissues and their accumulation in pediatric patients with chemotherapy.. PMID: 35895679, PMC: PMC9351471. Link: https://pubmed.ncbi.nlm.nih.gov/35895679/
242.A fixed mutation in the respiratory complex I impairs mitochondrial bioenergetics in the endangered Apennine brown bear.. PMID: 41026818, PMC: PMC12519208. Link: https://pubmed.ncbi.nlm.nih.gov/41026818/
244.Genomic evidence for demographic fluctuations, genetic burdens and adaptive divergence in fourfinger threadfin Eleutheronema rhadinum.. PMID: 40027332, PMC: PMC11871173. Link: https://pubmed.ncbi.nlm.nih.gov/40027332/
248.How should we measure population-level inbreeding depression? Impacts of standing genetic associations between selfing rate and deleterious mutations.. PMID: 39045597, PMC: PMC11263115. Link: https://pubmed.ncbi.nlm.nih.gov/39045597/
253.Genome sequences and population genomics provide insights into the demographic history, inbreeding, and mutation load of two ‘living fossil’ tree species of Dipteronia.. PMID: 37797086. Link: https://pubmed.ncbi.nlm.nih.gov/37797086/
260.An evolutionary perspective on genetic load in small, isolated populations as informed by whole genome resequencing and forward-time simulations.. PMID: 36626799. Link: https://pubmed.ncbi.nlm.nih.gov/36626799/
264.Mitonuclear Mismatch is Associated With Increased Male Frequency, Outcrossing, and Male Sperm Size in Experimentally-Evolved C. elegans.. PMID: 35360860, PMC: PMC8961728. Link: https://pubmed.ncbi.nlm.nih.gov/35360860/
273.The evolution of metapopulation dynamics and the number of stem cells in intestinal crypts and other tissue structures in multicellular bodies.. PMID: 32821281, PMC: PMC7428809. Link: https://pubmed.ncbi.nlm.nih.gov/32821281/
281.A chromosome-scale genome and transcriptomic analysis of the endangered tropical tree Vatica mangachapoi (Dipterocarpaceae ).. PMID: 35171284, PMC: PMC8882376. Link: https://pubmed.ncbi.nlm.nih.gov/35171284/
288.Two-dimensional IR spectroscopy of the anti-HIV agent KP1212 reveals protonated and neutral tautomers that influence pH-dependent mutagenicity.. PMID: 25733867, PMC: PMC4371980. Link: https://pubmed.ncbi.nlm.nih.gov/25733867/
289.Tautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside 5-aza-5,6-dihydro-2′-deoxycytidine.. PMID: 25071207, PMC: PMC4136561. Link: https://pubmed.ncbi.nlm.nih.gov/25071207/
299.Genetic Entropy and the Mystery of the Genome.. ISBN: 978-0981631608. (Sanford, 2008 ).