Genetic load and biological changes to extant humans

2020 ◽  
pp. 1-4
Author(s):  
Arthur Saniotis ◽  
Maciej Henneberg ◽  
Kazhaleh Mohammadi
Keyword(s):  
Natural Selection ◽  
Current Knowledge ◽  
Genetic Load ◽  
Differential Fertility ◽  
Medical Interventions ◽  
Deleterious Alleles ◽  
Gradual Process ◽  
Genetic Complexity ◽  
Sexual Recombination ◽  
Improved Sanitation

Abstract Extant humans are currently increasing their genetic load, which is informing present and future human microevolution. This has been a gradual process that has been rising over the last centuries as a consequence of improved sanitation, nutritional improvements, advancements in microbiology and medical interventions, which have relaxed natural selection. Moreover, a reduction in infant and child mortality and changing societal attitudes towards fertility have led to a decrease in total fertility rates (TFRs) since the 19th century. Generally speaking, decreases in differential fertility and mortality have meant that there is less opportunity for natural selection to eliminate deleterious mutations from the human gene pool. It has been argued that the average human may carry ~250–300 mutations that are mostly deleterious, as well as several hundred less-deleterious variants. These deleterious alleles in extant humans mean that our fitness is being constrained. While such alleles are viewed as reducing human fitness, they may also have had an adaptive function in the past, such as assisting in genetic complexity, sexual recombination and diploidy. Saying this, our current knowledge on these fitness compromising alleles is still lacking.

scholarly journals GENETIC LOAD IN NATURAL POPULATIONS: IS IT COMPATIBLE WITH THE HYPOTHESIS THAT MANY POLYMORPHISMS ARE MAINTAINED BY NATURAL SELECTION?

Genetics ◽  
1974 ◽  
Vol 77 (3) ◽  
pp. 569-589
Author(s):  
Martin L Tracey ◽  
Francisco J Ayala
Keyword(s):  
Drosophila Melanogaster ◽  
Natural Selection ◽  
Natural Population ◽  
Natural Populations ◽  
Genetic Load ◽  
Structural Genes ◽  
Invertebrate Species ◽  
Average Proportion ◽  
Mean Fitness ◽  
The Mean

ABSTRACT Recent studies of genetically controlled enzyme variation lead to an estimation that at least 30 to 60% of the structural genes are polymorphic in natural populations of many vertebrate and invertebrate species. Some authors have argued that a substantial proportion of these polymorphisms cannot be maintained by natural selection because this would result in an unbearable genetic load. If many polymorphisms are maintained by heterotic natural selection, individuals with much greater than average proportion of homozygous loci should have very low fitness. We have measured in Drosophila melanogaster the fitness of flies homozygous for a complete chromosome relative to normal wild flies. A total of 37 chromosomes from a natural population have been tested using 92 experimental populations. The mean fitness of homozygous flies is 0.12 for second chromosomes, and 0.13 for third chromosomes. These estimates are compatible with the hypothesis that many (more than one thousand) loci are maintained by heterotic selection in natural populations of D. melanogaster.

scholarly journals Dynamics of natural selection in two generations (on the example of the population of the Kirovograd region)

2021 ◽  
Vol 29 ◽  
pp. 152-156
Author(s):  
K. K. Kovleva ◽  
N.A. Kozak
Keyword(s):  
Natural Selection ◽  
First Generation ◽  
Second Generation ◽  
Selection Index ◽  
Genetic Load ◽  
Modern Medicine ◽  
Reproductive Age ◽  
Human Populations ◽  
Medical Histories ◽  
Total Selection

Aim. In connection with the success of modern medicine, the pressure of natural selection in various civilized human populations is weakening, which leads to the accumulation of a genetic load. The purpose of this work was to trace the change in the intensity of natural selection among population of the Kirovograd region in two successive generations. Methods. The collection of material was carried out in 2020 and 2021. Anonymous questionnaires were conducted and medical histories of women of post-reproductive age of the Kirovograd region were studied. The first generation included 40 women born in 1937–1959; the second generation consists of 273 women born in 1960–1981. Results. The total selection index was 0.27 in the first generation, and 0.37 in the second generation. The percentage of women who have not had pregnancies increased from the first generation to the second from 2.5 to 3.7, respectively. Conclusions. The index of total selection in the Kirovograd region population for one generation increased by almost one and a half times (from 0.27 to 0.37), as well as the index of differential fertility (from 0.25 to 0.35). Keywords: reproductive characteristics, Kirovograd population, Crow's index, selection, generations.

An Electron-Microscope Study of the Intranucleolar Chromatin in Root Meristematic Cells of Allium Cepa

1974 ◽  
Vol 15 (3) ◽  
pp. 645-657
Author(s):  
L. A. CHOUINARD
Keyword(s):  
Electron Microscope ◽  
Allium Cepa ◽  
Current Knowledge ◽  
General Concept ◽  
Condensed Chromatin ◽  
Condensed State ◽  
Interphase Cell ◽  
Gradual Process ◽  
Nucleolar Chromosome ◽  
Chromatin Material

The various states of condensation and configuration of the chromatin material, contained inside the lacunar regions of the interphase nucleolus in Allium cepa, have been investigated by means of conventional electron-microscope techniques. The observations reveal that in a number of lacunar profiles, the chromatin material in question appears in an extended state only; in other lacunar profiles of the same or different nucleoli, the chromatin material is present both in an extended and a condensed condition. Moreover, in some lacunar profiles, a single mass of chromatin in a condensed state is observed; in others, several discrete and often seemingly interconnected masses of condensed chromatin are visualized. An attempt is made to interpret these morphological findings in the light of current knowledge concerning the structural relationship of the nucleolar organizing segment of the nucleolar chromosome with the interphase nucleolus in plant cells. The relevant observational evidence would be consistent with the view that the chromatin-containing lacunar regions of the interphase nucleolus in Allium cepa correspond, in fact, to cross or oblique sections of a meandering channel through which the nucleolar organizing segment of the nucleolar chromosome passes. Assuming the applicability to intranucleolar chromatin of the general concept of condensed-inactive versus extended-active chromatin, it is hypothesized that the various states of condensation of intralacunar chromatin merely reflect variations in the functional activity of the nucleolar organizing segment during the interphase cell cycle in the species investigated. With regard to variations in the configurational state of the intralacunar condensed chromatin, it is postulated that they are the cytological expression of the gradual process of coiling or folding upon itself of the nucleolar organizing segment during late interphase and in preparation for the next mitosis.

scholarly journals Sexual Selection Does Not Increase the Rate of Compensatory Adaptation to a Mutation Influencing a Secondary Sexual Trait in Drosophila melanogaster

2020 ◽  
Vol 10 (5) ◽  
pp. 1541-1551
Author(s):  
Christopher H. Chandler ◽  
Anna Mammel ◽  
Ian Dworkin
Keyword(s):  
Drosophila Melanogaster ◽  
Sexual Selection ◽  
Natural Selection ◽  
Spontaneous Mutation ◽  
Phenotypic Expression ◽  
Theoretical Work ◽  
Phenotypic Suppression ◽  
Compensatory Adaptation ◽  
Deleterious Alleles ◽  
Sex Comb

Theoretical work predicts that sexual selection can enhance natural selection, increasing the rate of adaptation to new environments and helping purge harmful mutations. While some experiments support these predictions, remarkably little work has addressed the role of sexual selection on compensatory adaptation—populations’ ability to compensate for the costs of deleterious alleles that are already present. We tested whether sexual selection, as well as the degree of standing genetic variation, affect the rate of compensatory evolution via phenotypic suppression in experimental populations of Drosophila melanogaster. These populations were fixed for a spontaneous mutation causing mild abnormalities in the male sex comb, a structure important for mating success. We fine-mapped this mutation to an ∼85 kb region on the X chromosome containing three candidate genes, showed that the mutation is deleterious, and that its phenotypic expression and penetrance vary by genetic background. We then performed experimental evolution, including a treatment where opportunity for mate choice was limited by experimentally enforced monogamy. Although evolved populations did show some phenotypic suppression of the morphological abnormalities in the sex comb, the amount of suppression did not depend on the opportunity for sexual selection. Sexual selection, therefore, may not always enhance natural selection; instead, the interaction between these two forces may depend on additional factors.

scholarly journals Evolutionary stalling and a limit on the power of natural selection to improve a cellular module

2020 ◽  
Vol 117 (31) ◽  
pp. 18582-18590 ◽  
Author(s):  
Sandeep Venkataram ◽  
Ross Monasky ◽  
Shohreh H. Sikaroodi ◽  
Sergey Kryazhimskiy ◽  
Betul Kacar
Keyword(s):  
Escherichia Coli ◽  
Natural Selection ◽  
Adaptive Evolution ◽  
Genetic Load ◽  
Performance Theory ◽  
Biological Functions ◽  
Beneficial Mutations ◽  
Translation Machinery ◽  
Adaptive Mutations ◽  
Organismal Fitness

Cells consist of molecular modules which perform vital biological functions. Cellular modules are key units of adaptive evolution because organismal fitness depends on their performance. Theory shows that in rapidly evolving populations, such as those of many microbes, adaptation is driven primarily by common beneficial mutations with large effects, while other mutations behave as if they are effectively neutral. As a consequence, if a module can be improved only by rare and/or weak beneficial mutations, its adaptive evolution would stall. However, such evolutionary stalling has not been empirically demonstrated, and it is unclear to what extent stalling may limit the power of natural selection to improve modules. Here we empirically characterize how natural selection improves the translation machinery (TM), an essential cellular module. We experimentally evolved populations ofEscherichia coliwith genetically perturbed TMs for 1,000 generations. Populations with severe TM defects initially adapted via mutations in the TM, but TM adaptation stalled within about 300 generations. We estimate that the genetic load in our populations incurred by residual TM defects ranges from 0.5 to 19%. Finally, we found evidence that both epistasis and the depletion of the pool of beneficial mutations contributed to evolutionary stalling. Our results suggest that cellular modules may not be fully optimized by natural selection despite the availability of adaptive mutations.

scholarly journals Management of Cardiac Toxicity Induced by Chemotherapy

2020 ◽  
Vol 9 (9) ◽  
pp. 2885 ◽  
Author(s):  
Dario Trapani ◽  
Paola Zagami ◽  
Eleonora Nicolò ◽  
Gabriella Pravettoni ◽  
Giuseppe Curigliano
Keyword(s):  
Clinical Decision Making ◽  
Current Knowledge ◽  
Early Recognition ◽  
Clinical Decision ◽  
Cancer Treatments ◽  
Drug Induced ◽  
Medical Interventions ◽  
Clinical Scenarios ◽  
New Biomarkers ◽  
Chemotherapy Agents

Cardiotoxicity encompasses a spectrum of adverse cardiological effects experienced by cancer patients during and after receiving antineoplastic treatments. The intersection of cancer care with the management of the multiple comorbid non-communicable diseases carried by patients or related to cancer treatments motivates the need for an integrated and multidisciplinary approach to therapeutic clinical decision-making. This present review aimed to provide a perspective and an update of the current pharmacotherapy approaches for the prevention and management of cardiotoxicity from antiblastic chemotherapy; as such, it addresses myocardial, vascular, and arrhythmic disorders associated to chemotherapy, by navigating the current knowledge and clinical indications in support of the medical interventions. Clinical scenarios of pharmacological interventions take place with patients receiving anthracycline and, by extrapolation, other agents with cardiotoxic potentials and non-chemotherapy agents, including various small molecules and immunotherapy agents. Analysis of these scenarios aims to provide practical evidence-based guidance for the management of drug-induced cardiac dysfunctions. The possible role of new biomarkers for the early recognition of cardiotoxicity is mentioned across the clinical studies, with reference to the pharmacological biomarker-driven interventions delivered. To best inform survivorship care, the management and context of cardio-oncology services are discussed within the broader network of providers and settings of care.

scholarly journals Butterfly survival on an isolated island by improved grip

2013 ◽  
Vol 9 (2) ◽  
pp. 20130020 ◽  
Author(s):  
Anne Duplouy ◽  
Ilkka Hanski
Keyword(s):  
Genetic Variation ◽  
Natural Selection ◽  
Local Adaptation ◽  
Genetic Load ◽  
High Rate ◽  
Dispersal Capacity ◽  
Flight Capacity ◽  
Butterfly Population

On small isolated islands, natural selection is expected to reduce the dispersal capacity of organisms, as short distances do not require a high rate of dispersal, which might lead to accidental emigration from the population. In addition, individuals foregoing the high cost of maintaining flight capacity may instead allocate resources to other functions. However, in butterflies and many other insects, flight is necessary not only for dispersal but also for most other activities. A weakly flying individual would probably do worse and have an elevated rather than reduced probability of accidental emigration. Here, we report results consistent with the hypothesis that a butterfly population on an isolated island, instead of having lost its flight capacity, has evolved better grip to resist the force of wind and to avoid being blown off the island. Our study suggests that local adaptation has occurred in this population in spite of its very small size ( N e ∼ 100), complete isolation, low genetic variation and high genetic load.

scholarly journals Sex differences in deleterious genetic variants in a haplodiploid social insect

2021 ◽  
Author(s):  
Sara E. Miller ◽  
Michael J. Sheehan
Keyword(s):  
Genetic Load ◽  
Low Frequency ◽  
Paper Wasp ◽  
Deleterious Mutations ◽  
Wild Populations ◽  
Nonsense Mutations ◽  
Low Frequencies ◽  
Complete Dominance ◽  
Deleterious Alleles ◽  
Population Allele Frequency

AbstractDeleterious variants are selected against but can linger in populations at low frequencies for long periods of time, decreasing fitness and contributing to disease burden in humans and other species. Deleterious variants occur at low frequency but distinguishing deleterious variants from low frequency neutral variation is challenging based on population genetics data. As a result, we have little sense of the number and identity of deleterious variants in wild populations. For haplodiploid species, it has been hypothesized that deleterious alleles will be directly exposed to selection in haploid males, but selection can be masked in diploid females due to partial or complete dominance, resulting in more efficient purging of deleterious mutations in males. Therefore, comparisons of the differences between haploid and diploid genomes from the same population may be a useful method for inferring rare deleterious variants. This study provides the first formal test of this hypothesis. Using wild populations of Northern paper wasps (Polistes fuscatus), we find that males have fewer overall variants, and specifically fewer missense and nonsense variants, than females from the same population. Allele frequency differences are especially pronounced for rare missense and nonsense mutations and these differences lead to a lower genetic load in males than females. Based on these data we estimate that a large number of highly deleterious mutations are segregating in the paper wasp population. Stronger selection against deleterious alleles in haploid males may have implications for adaptation in other haplodiploid insects and provides evidence that wild populations harbor abundant deleterious variants.

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