The efficacy of means exploited currently for cancer prevention and treatment appeared to be very low. New insights into the origin of the disease are sorely needed. The present article synthesizes the results from in...The efficacy of means exploited currently for cancer prevention and treatment appeared to be very low. New insights into the origin of the disease are sorely needed. The present article synthesizes the results from integrative reconsideration of actual data on cancer from the viewpoint of recent developments in pathology, epidemiology, immunology, genetics, and evolution. In contrast to the 80 years old hypothesis of somatic mutative origin of carcinogenesis, the revealed set of evidence showed the origin of cancerous clones is based on inherent constitutional incongruence between the regulators of cell physiology and their targets realized in inherent immunity of cancerous cells to normal regulation of cell replication and tissue growth. The incongruence arises out of both genome mutations which led to interethnic differences in the regulator-receptor structures and intercourse between ethnoses, the regulator-receptor evolution of which has been processed to deal with different ecologic conditions. The current pandemic spread of cancer is brought about growing expansion of interethnic xenogamy favored by growing industrialization, urbanization, globalization, and migration. The proposed hypothesis of genome intrusion in the origin of cancer induces new research ideas and proposals for cancer prevention and therapy.展开更多
The evolution of sex is one of the most important and controversial problems in evolutionary biology.Although sex is almost universal in higher animals and plants,its inherent costs have made its maintenance difficult...The evolution of sex is one of the most important and controversial problems in evolutionary biology.Although sex is almost universal in higher animals and plants,its inherent costs have made its maintenance difficult to explain.The most famous of these is the twofold cost of males,which can greatly reduce the fecundity of a sexual population,compared to a population of asexual females.Over the past century,multiple hypotheses,along with experimental evidence to support these,have been put forward to explain widespread costly sex.In this review,we outline some of the most prominent theories,along with the experimental and observational evidence supporting these.Historically,there have been 4 classes of theories:the ability of sex to fix multiple novel advantageous mutants(Fisher-Muller hypothesis);sex as a mechanism to stop the build-up of deleterious mutations in finite populations(Muller’s ratchet);recombination creating novel genotypes that can resist infection by parasites(Red Queen hypothesis);and the ability of sex to purge bad genomes if deleterious mutations act synergistically(mutational deterministic hypothesis).Current theoretical and experimental evidence seems to favor the hypothesis that sex breaks down selection interference between new mutants,or it acts as a mechanism to shuffle genotypes in order to repel parasitic invasion.However,there is still a need to collect more data from natural populations and experimental studies,which can be used to test different hypotheses.展开更多
Mutation is a primary source of genetic variation that is used to power evolution.Many studies,however,have shown that most mutations are deleterious and,as a result,extremely low mutation rates might be benefcial for...Mutation is a primary source of genetic variation that is used to power evolution.Many studies,however,have shown that most mutations are deleterious and,as a result,extremely low mutation rates might be benefcial for survival.Using a mutation accumulation experiment,an unbiased method for mutation study,we found an extremely low base-substitution mutation rate of 5.94×10^(-11) per nucleotide site per cell division(95%Poisson confdence intervals:4.65×10^(-11),7.48×10^(-11))and indel mutation rate of 8.25×10^(-12) per site per cell division(95%confdence intervals:3.96×10^(-12),1.52×10^(-11))in the bacterium Photorhabdus luminescens ATCC29999.The mutations are strongly A/T-biased with a mutation bias of 10.28 in the A/T direction.It has been hypothesized that the ability for selection to lower mutation rates is inversely proportional to the efective population size(drift-barrier hypothesis)and we found that the efective population size of this bacterium is signifcantly greater than most other bacteria.This fnding further decreases the lower-bounds of bacterial mutation rates and provides evidence that extreme levels of replication fdelity can evolve within organisms that maintain large efective population sizes.展开更多
文摘The efficacy of means exploited currently for cancer prevention and treatment appeared to be very low. New insights into the origin of the disease are sorely needed. The present article synthesizes the results from integrative reconsideration of actual data on cancer from the viewpoint of recent developments in pathology, epidemiology, immunology, genetics, and evolution. In contrast to the 80 years old hypothesis of somatic mutative origin of carcinogenesis, the revealed set of evidence showed the origin of cancerous clones is based on inherent constitutional incongruence between the regulators of cell physiology and their targets realized in inherent immunity of cancerous cells to normal regulation of cell replication and tissue growth. The incongruence arises out of both genome mutations which led to interethnic differences in the regulator-receptor structures and intercourse between ethnoses, the regulator-receptor evolution of which has been processed to deal with different ecologic conditions. The current pandemic spread of cancer is brought about growing expansion of interethnic xenogamy favored by growing industrialization, urbanization, globalization, and migration. The proposed hypothesis of genome intrusion in the origin of cancer induces new research ideas and proposals for cancer prevention and therapy.
文摘The evolution of sex is one of the most important and controversial problems in evolutionary biology.Although sex is almost universal in higher animals and plants,its inherent costs have made its maintenance difficult to explain.The most famous of these is the twofold cost of males,which can greatly reduce the fecundity of a sexual population,compared to a population of asexual females.Over the past century,multiple hypotheses,along with experimental evidence to support these,have been put forward to explain widespread costly sex.In this review,we outline some of the most prominent theories,along with the experimental and observational evidence supporting these.Historically,there have been 4 classes of theories:the ability of sex to fix multiple novel advantageous mutants(Fisher-Muller hypothesis);sex as a mechanism to stop the build-up of deleterious mutations in finite populations(Muller’s ratchet);recombination creating novel genotypes that can resist infection by parasites(Red Queen hypothesis);and the ability of sex to purge bad genomes if deleterious mutations act synergistically(mutational deterministic hypothesis).Current theoretical and experimental evidence seems to favor the hypothesis that sex breaks down selection interference between new mutants,or it acts as a mechanism to shuffle genotypes in order to repel parasitic invasion.However,there is still a need to collect more data from natural populations and experimental studies,which can be used to test different hypotheses.
基金This work is supported by the Young Taishan Scholars Program of Shandong Province(tsqn201812024)the Fundamental Research Funds for the Central Universities of China(201822020)to H.L.+1 种基金the Multidisciplinary University Research Initiative Award from the US Army Research Ofce(W911NF-09-1-0444 and W911NF-09-1-0411)National Institutes of Health award(R35-GM122566)to M.L.
文摘Mutation is a primary source of genetic variation that is used to power evolution.Many studies,however,have shown that most mutations are deleterious and,as a result,extremely low mutation rates might be benefcial for survival.Using a mutation accumulation experiment,an unbiased method for mutation study,we found an extremely low base-substitution mutation rate of 5.94×10^(-11) per nucleotide site per cell division(95%Poisson confdence intervals:4.65×10^(-11),7.48×10^(-11))and indel mutation rate of 8.25×10^(-12) per site per cell division(95%confdence intervals:3.96×10^(-12),1.52×10^(-11))in the bacterium Photorhabdus luminescens ATCC29999.The mutations are strongly A/T-biased with a mutation bias of 10.28 in the A/T direction.It has been hypothesized that the ability for selection to lower mutation rates is inversely proportional to the efective population size(drift-barrier hypothesis)and we found that the efective population size of this bacterium is signifcantly greater than most other bacteria.This fnding further decreases the lower-bounds of bacterial mutation rates and provides evidence that extreme levels of replication fdelity can evolve within organisms that maintain large efective population sizes.
