Medical Genetic Polymorphisms as Markers of Evolutionary Forces Within the Human Genome: Hypotheses Focusing on Natural Selection in the Basque Population

The evolution of a population by means of genetic drift and natural selection operating on a gene regulatory network (GRN) of an individual has not been scrutinized in depth. Thus, the relative importance of various evolutionary forces and processes on shaping genetic variability in GRNs is understudied. Furthermore, it is not known if existing tools that identify recent and strong positive selection from genomic sequences, in simple models of evolution, can detect recent positive selection when it operates on GRNs. Here, we propose a simulation framework, called EvoNET, that simulates forward-in-time the evolution of GRNs in a population. Since the population size is finite, random genetic drift is explicitly applied. The fitness of a mutation is not constant, but we evaluate the fitness of each individual by measuring its genetic distance from an optimal genotype. Mutations and recombination may take place from generation to generation, modifying the genotypic composition of the population. Each individual goes through a maturation period, where its GRN reaches equilibrium. At the next step, individuals compete to produce the next generation. As time progresses, the beneficial genotypes push the population higher in the fitness landscape. We examine properties of the GRN evolution such as robustness against the deleterious effect of mutations and the role of genetic drift. We confirm classical results from Andreas Wagner’s work that GRNs show robustness against mutations and we provide new results regarding the interplay between random genetic drift and natural selection.

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Characterization of a Pseudomonas putida Rough Variant Evolved in a Mixed-Species Biofilm with Acinetobacter sp. Strain C6

Journal of Bacteriology ◽

10.1128/jb.00041-07 ◽

2007 ◽

Vol 189 (13) ◽

pp. 4932-4943 ◽

Cited By ~ 50

Author(s):

Susse Kirkelund Hansen ◽

Janus A. J. Haagensen ◽

Morten Gjermansen ◽

Thomas Martini Jørgensen ◽

Tim Tolker-Nielsen ◽

...

Keyword(s):

Natural Selection ◽

Pseudomonas Putida ◽

Wild Type ◽

Low Oxygen ◽

Phenotypic Characteristics ◽

Mixed Species ◽

Evolutionary Forces ◽

Enhanced Production ◽

Oxygen Starvation ◽

Biofilm Development

ABSTRACT Genetic differentiation by natural selection is readily observed among microbial populations, but a more comprehensive understanding of evolutionary forces, genetic causes, and resulting phenotypic advantages is not often sought. Recently, a surface population of Pseudomonas putida bacteria was shown to evolve rapidly by natural selection of better-adapted variants in a mixed-species biofilm consortium (S. K. Hansen, P. B. Rainey, J. A. Haagensen, and S. Molin, Nature 445:533-536, 2007). Adaptation was caused by mutations in a wapH homolog (PP4943) involved in core lipopolysaccharide biosynthesis. Here we investigate further the biofilm physiology and the phenotypic characteristics of the selected P. putida rough colony variants. The coexistence of the P. putida population in a mixed-species biofilm with Acinetobacter sp. strain C6 is dependent on the benzoate excreted from Acinetobacter during the catabolism of benzyl alcohol, the sole carbon source. Examination of biofilm development and the dynamics of the wild-type consortium revealed that the biofilm environment became oxygen limited, possibly with low oxygen concentrations around Acinetobacter microcolonies. In contrast to P. putida wild-type cells, which readily dispersed from the mixed-species biofilm in response to oxygen starvation, the rough variant cells displayed a nondispersal phenotype. However, in monospecies biofilms proliferating on benzoate, the rough variant (like the wild-type population) dispersed in response to oxygen starvation. A key factor explaining this conditional, nondispersal phenotype is likely to be the acquired ability of the rough variant to coaggregate specifically with Acinetobacter cells. We further show that the P. putida rough variant displayed enhanced production of a cellulose-like polymer as a consequence of the mutation in wapH. The resulting phenotypic characteristics of the P. putida rough variant explain its enhanced fitness and ability to form tight structural associations with Acinetobacter microcolonies.

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Century-scale Holocene processes as a source of natural selection pressure in human evolution: Holocene climate and the Human Genome Project

The Holocene ◽

10.1177/0959683607079003 ◽

2007 ◽

Vol 17 (5) ◽

pp. 689-695 ◽

Cited By ~ 1

Author(s):

Alison J. Smith

Keyword(s):

Natural Selection ◽

Human Genome ◽

Human Evolution ◽

Human Genome Project ◽

Selection Pressure ◽

Genome Project ◽

Holocene Climate ◽

The Human Genome Project

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Genetic polymorphism of Plasmodium falciparum circumsporozoite protein (PfCSP) and mismatches against RTS, S/AS01 malaria vaccine observed on Bioko Island, Equatorial Guinea and globally

10.21203/rs.2.22549/v1 ◽

2020 ◽

Author(s):

Hui-Ying Huang ◽

Xue-Yan Liang ◽

Li-Yun Lin ◽

Jiang-Tao Chen ◽

Carlos Salas Ehapo ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Natural Selection ◽

Genetic Polymorphism ◽

Genetic Polymorphisms ◽

Vaccine Efficacy ◽

Malaria Vaccine ◽

Repetitive Sequences ◽

Circumsporozoite Protein ◽

Bioko Island ◽

Selection Of

Abstract Backgroud RTS, S/AS01 is a Plasmodium falciparum circumsporozoite protein ( PfCSP ) based anti-malaria vaccine, but various genetic polymorphisms of PfCSP among global P. falciparum population could lead to mismatch against the PfCSP - based vaccine and reduce vaccine efficacy. This study aimed to investigate the genetic polymorphisms and natural selection of PfCSP in Bioko as well as global P. falciparum population. Methods From January 2011 to December 2018, 148 blood samples were collected from P. falciparum infected Bioko patients and 96 monoclonal sequences of them were successfully acquired and analyzed with 2200 global PfCSP sequences mined from MalariaGEN Pf3k Database and NCBI. Results In Bioko, the N-terminus of PfCSP showed limited genetic variations and the numbers of repetitive sequences (NANP/NVDP) were mainly found as 40 (35%) and 41 (34%) in central region. Most polymorphic characters were found in Th2R/Th3R region, where natural selection (p>0.05) and recombination occurred. The overall pattern of Bioko PfCSP gene had no obvious deviation from African mainland PfCSP (Fst=0.00878, p<0.05). The comparative analysis of Bioko and global PfCSP displayed the various mutation patterns and obvious geographic differentiation among populations from four continents (p<0.05). The global PfCSP C-terminal sequences were clustered into 138 different haplotypes (H_1 to H_138). Only 3.35% of sequences matched 3D7 vaccine strain haplotype (H_1). Conclusions The genetic polymorphism phenomena of PfCSP were found universal. The overall vaccine efficacy might be influenced by the low proportion of vaccine-matched isolates in global parasites population. Genetic polymorphism and geographical characteristics should be considered for future improvement of RTS, S/AS01.

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Spontaneous mutations and the origin and maintenance of quantitative genetic variation

eLife ◽

10.7554/elife.14625 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 26

Author(s):

Wen Huang ◽

Richard F Lyman ◽

Rachel A Lyman ◽

Mary Anna Carbone ◽

Susan T Harbison ◽

...

Keyword(s):

Genetic Variation ◽

Natural Selection ◽

Quantitative Traits ◽

Spontaneous Mutation ◽

Natural Populations ◽

Empirical Work ◽

Stabilizing Selection ◽

Spontaneous Mutation Rate ◽

Evolutionary Forces ◽

Quantitative Genetic

Mutation and natural selection shape the genetic variation in natural populations. Here, we directly estimated the spontaneous mutation rate by sequencing new Drosophila mutation accumulation lines maintained with minimal natural selection. We inferred strong stabilizing natural selection on quantitative traits because genetic variation among wild-derived inbred lines was much lower than predicted from a neutral model and the mutational effects were much larger than allelic effects of standing polymorphisms. Stabilizing selection could act directly on the traits, or indirectly from pleiotropic effects on fitness. However, our data are not consistent with simple models of mutation-stabilizing selection balance; therefore, further empirical work is needed to assess the balance of evolutionary forces responsible for quantitative genetic variation.

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Untangling the Mathematical Relation Between Natural Selection and Adaptive Radiation Using Macromolecules and Microevolutionary Forces

International Journal of Scientific Research in Science and Technology ◽

10.32628/ijsrst207260 ◽

2020 ◽

pp. 313-339

Author(s):

Bharat Kwatra ◽

Maanvi Mudgil

Keyword(s):

Natural Selection ◽

Dna Fingerprinting ◽

Adaptive Radiation ◽

Environment Interaction ◽

Male And Female ◽

Evolutionary Forces ◽

Gene Environment Interaction ◽

Gene Environment ◽

Mathematical Relation

Simulating natural selection over subsequent generations of Oniscus asellus, the fittest selected male and female bugs in different diet was used to analyze the concentration of proteins in their body along their frequency in continuous mapped generations over hundred seed values, further DNA Fingerprinting of these selected bugs revealed a relationship with their parents originated from different geographic areas/borders. It was observed that variation in microevolutionary forces caused variation in macromolecules by setting up a gene-environment interaction which deduced natural selection in order to define adaptive radiation and speciation by micro-evolutionary forces.

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Robust detection of natural selection using a probabilistic model of tree imbalance

10.1101/2021.05.12.443797 ◽

2021 ◽

Author(s):

Enes Dilber ◽

Jonathan Terhorst

Keyword(s):

Natural Selection ◽

Open Source Software ◽

Probabilistic Model ◽

Simulated Data ◽

Population Expansion ◽

Effective Population ◽

Robust Detection ◽

Evolutionary Forces ◽

Tree Topologies ◽

Neutrality Tests

Neutrality tests such as Tajima's D and Fay and Wu's H are standard implements in the population genetics toolbox. One of their most common uses is to scan the genome for signals of natural selection. However, it is well understood that deviance measures like D and H are confounded by other evolutionary forces---in particular, population expansion---that may be unrelated to selection. Because they are not model-based, it is not clear how to deconfound these statistics in a principled way. In this paper we derive new likelihood-based methods for detecting natural selection which are robust to confounding by fluctuations in effective population size. At the core of our method is a novel probabilistic model of tree imbalance, which generalizes Kingman's coalescent to allow certain aberrant tree topologies to arise more frequently than is expected under neutrality. We derive a frequency spectrum-based estimator which can be used in place of D, and also extend to the case where genealogies are first estimated. We benchmark our methods on real and simulated data, and provide an open source software implementation.

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Detecting selection from linked sites using an F-model

10.1101/737916 ◽

2019 ◽

Cited By ~ 1

Author(s):

Marco Galimberti ◽

Christoph Leuenberger ◽

Beat Wolf ◽

Sándor Miklós Szilágyi ◽

Matthieu Foll ◽

...

Keyword(s):

Markov Model ◽

Human Genome ◽

Genetic Drift ◽

Statistical Power ◽

Hidden Markov ◽

Allele Frequencies ◽

Human Genome Diversity Project ◽

Genome Diversity ◽

Specific Component ◽

Evolutionary Forces

ABSTRACTAllele frequencies vary across populations and loci, even in the presence of migration. While most differences may be due to genetic drift, divergent selection will further increase differentiation at some loci. Identifying those is key in studying local adaptation, but remains statistically challenging. A particularly elegant way to describe allele frequency differences among populations connected by migration is the F-model, which measures differences in allele frequencies by population specific FST coefficients. This model readily accounts for multiple evolutionary forces by partitioning FST coefficients into locus and population specific components reflecting selection and drift, respectively. Here we present an extension of this model to linked loci by means of a hidden Markov model (HMM) that characterizes the effect of selection on linked markers through correlations in the locus specific component along the genome. Using extensive simulations we show that our method has up to two-fold the statistical power of previous implementations that assume sites to be independent. We finally evidence selection in the human genome by applying our method to data from the Human Genome Diversity Project (HGDP).

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A Chronological Atlas of Natural Selection in the Human Genome during the Past Half-million Years

10.1101/018929 ◽

2015 ◽

Cited By ~ 13

Author(s):

Hang Zhou ◽

Sile Hu ◽

Rostislav Matveev ◽

Qianhui Yu ◽

Jing Li ◽

...

Keyword(s):

Natural Selection ◽

Human Genome ◽

Cognitive Abilities ◽

Brain Function ◽

Balancing Selection ◽

Brain Evolution ◽

Modern Human ◽

Time Estimates ◽

Past Half ◽

Disease Pathways

The spatiotemporal distribution of recent human adaptation is a long standing question. We developed a new coalescent-based method that collectively assigned human genome regions to modes of neutrality or to positive, negative, or balancing selection. Most importantly, the selection times were estimated for all positive selection signals, which ranged over the last half million years, penetrating the emergence of anatomically modern human (AMH). These selection time estimates were further supported by analyses of the genome sequences from three ancient AMHs and the Neanderthals. A series of brain function-related genes were found to carry signals of ancient selective sweeps, which may have defined the evolution of cognitive abilities either before Neanderthal divergence or during the emergence of AMH. Particularly, signals of brain evolution in AMH are strongly related to Alzheimer's disease pathways. In conclusion, this study reports a chronological atlas of natural selection in Human.

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The colours of humanity: the evolution of pigmentation in the human lineage

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0349 ◽

2017 ◽

Vol 372 (1724) ◽

pp. 20160349 ◽

Cited By ~ 42

Author(s):

Nina G. Jablonski ◽

George Chaplin

Keyword(s):

Natural Selection ◽

Genetic Drift ◽

Homo Sapiens ◽

Skin Colour ◽

Population Bottlenecks ◽

Melanin Pigmentation ◽

Evolutionary Forces ◽

History Of ◽

Skin Coloration ◽

Perception Function

Humans are a colourful species of primate, with human skin, hair and eye coloration having been influenced by a great variety of evolutionary forces throughout prehistory. Functionally naked skin has been the physical interface between the physical environment and the human body for most of the history of the genus Homo , and hence skin coloration has been under intense natural selection. From an original condition of protective, dark, eumelanin-enriched coloration in early tropical-dwelling Homo and Homo sapiens , loss of melanin pigmentation occurred under natural selection as Homo sapiens dispersed into non-tropical latitudes of Africa and Eurasia. Genes responsible for skin, hair and eye coloration appear to have been affected significantly by population bottlenecks in the course of Homo sapiens dispersals. Because specific skin colour phenotypes can be created by different combinations of skin colour–associated genetic markers, loss of genetic variability due to genetic drift appears to have had negligible effects on the highly redundant genetic ‘palette’ for the skin colour. This does not appear to have been the case for hair and eye coloration, however, and these traits appear to have been more strongly influenced by genetic drift and, possibly, sexual selection. This article is part of the themed issue ‘Animal coloration: production, perception, function and application’.

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