scholarly journals Somatic drift and rapid loss of heterozygosity suggest small effective population size of stem cells and high somatic mutation rate in asexual planaria

2019 ◽  
Author(s):  
Hosseinali Asgharian ◽  
Joseph Dunham ◽  
Paul Marjoram ◽  
Sergey V. Nuzhdin

AbstractPlanarian flatworms have emerged as highly promising models of body regeneration due to the many stem cells scattered through their bodies. Currently, there is no consensus as to the number of stem cells active in each cycle of regeneration or the equality of their relative contributions. We approached this problem with a population genetic model of somatic genetic drift. We modeled the fissiparous life cycle of asexual planarians as an asexual population of cells that goes through repeated events of splitting into two subpopulations followed by population growth to restore the original size. We sampled a pedigree of obligate asexual clones of Girardia cf. tigrina at multiple time points encompassing 14 generations. Effective population size of stem cells was inferred from the magnitude of temporal fluctuations in the frequency of somatic variants and under most of the examined scenarios was estimated to be in the range of a few hundreds. Average genomic nucleotide diversity was 0.00398. Assuming neutral evolution and mutation-drift equilibrium, the somatic mutation rate was estimated in the 10−5 − 10−7 range. Alternatively, we estimated Ne and somatic μ from temporal changes in nucleotide diversity π without the assumption of equilibrium. This second method suggested even smaller Ne and larger μ. A key unknown parameter in our model on which estimates of Ne and μ depend is g, the ratio of cellular to organismal generations determined by tissue turnover rate. Small effective number of propagating stem cells might contribute to reducing reproductive conflicts in clonal organisms.


1982 ◽  
Vol 39 (3) ◽  
pp. 303-314 ◽  
Author(s):  
Ranajit Chakraborty ◽  
Masatoshi Nei

SummaryIntroducing a new genetic model called the discrete allelic-state model, the evolutionary change of genetic variation of quantitative characters within and between populations is studied under the assumption of no selection. This model allows us to study the effects of mutation and random genetic drift in detail. It is shown that when the allelic effects on phenotype are additive, the rate of approach of the genetic variance within populations to the equilibrium value depends only on the effective population size. It is also shown that the distribution of genotypic value often deviates from normality particularly when the effective population size and the number of loci concerned are small. On the other hand, the interpopulational variance increases linearly with time, if the intrapopu-lational variance remains constant. Therefore, the ratio of interpopulational variance to intrapopulational variance can be used for testing the hypothesis of neutral evolution of quantitative characters.



PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2549 ◽  
Author(s):  
Séverine Fourdrilis ◽  
Patrick Mardulyn ◽  
Olivier J. Hardy ◽  
Kurt Jordaens ◽  
António Manuel de Frias Martins ◽  
...  

We report the presence of mitochondrial DNA (mtDNA) hyperdiversity in the marine periwinkleMelarhaphe neritoides(Linnaeus, 1758), the first such case among marine gastropods. Our dataset consisted of concatenated 16S-COI-Cytbgene fragments. We used Bayesian analyses to investigate three putative causes underlying genetic variation, and estimated the mtDNA mutation rate, possible signatures of selection and the effective population size of the species in the Azores archipelago. The mtDNA hyperdiversity inM. neritoidesis characterized by extremely high haplotype diversity (Hd= 0.999 ± 0.001), high nucleotide diversity (π= 0.013 ± 0.001), and neutral nucleotide diversity above the threshold of 5% (πsyn= 0.0677). Haplotype richness is very high even at spatial scales as small as 100m2. Yet, mtDNA hyperdiversity does not affect the ability of DNA barcoding to identifyM. neritoides. The mtDNA hyperdiversity inM. neritoidesis best explained by the remarkably high mutation rate at the COI locus (μ= 5.82 × 10−5per site per yearorμ= 1.99 × 10−4mutations per nucleotide site per generation), whereas the effective population size of this planktonic-dispersing species is surprisingly small (Ne= 5, 256; CI = 1,312–3,7495) probably due to the putative influence of selection. Comparison with COI nucleotide diversity values in other organisms suggests that mtDNA hyperdiversity may be more frequently linked to highμvalues and that mtDNA hyperdiversity may be more common across other phyla than currently appreciated.



Genetics ◽  
1994 ◽  
Vol 136 (2) ◽  
pp. 685-692 ◽  
Author(s):  
Y X Fu

Abstract A new estimator of the essential parameter theta = 4Ne mu from DNA polymorphism data is developed under the neutral Wright-Fisher model without recombination and population subdivision, where Ne is the effective population size and mu is the mutation rate per locus per generation. The new estimator has a variance only slightly larger than the minimum variance of all possible unbiased estimators of the parameter and is substantially smaller than that of any existing estimator. The high efficiency of the new estimator is achieved by making full use of phylogenetic information in a sample of DNA sequences from a population. An example of estimating theta by the new method is presented using the mitochondrial sequences from an American Indian population.



Genetics ◽  
2004 ◽  
Vol 166 (1) ◽  
pp. 555-563 ◽  
Author(s):  
Hongyan Xu ◽  
Yun-Xin Fu


Genetics ◽  
1980 ◽  
Vol 95 (2) ◽  
pp. 489-502
Author(s):  
Susan R Wilson

ABSTRACT The statistical methods used by SCHAFFER, YARDLEY and ANDERSON (1977) and by GIBSON et al. (1979) to analyze the variation in allele frequencies in two common types of experimental procedure, where the effective population size is finite, are extended to a more general situation involving a greater range of experiments. The analysis developed is more sensitive in detecting changes in allele frequency due to both fluctuating and balancing selection, as well as to directional selection. The error involved in many studies due to ignoring the effective population size structure would appear to be large. The range of hypotheses that can be considered may be increased as well. Finally, the method of determining bounds for the effective population size, when a particular genetic model is known to hold for a data set, is also outlined.



Genetics ◽  
1977 ◽  
Vol 85 (2) ◽  
pp. 331-337
Author(s):  
Wen-Hsiung Li

ABSTRACT Watterson's (1975) formula for the steady-state distribution of the number of nucleotide differences between two randomly chosen cistrons in a finite population has been extended to transient states. The rate for the mean of this distribution to approach its equilibrium value is 1/2 N and independent of mutation rate, but that for the variance is dependent on mutation rate, where N denotes the effective population size. Numerical computations show that if the heterozygosity (i.e., the probability that two cistrons are different) is low, say of the order of 0.1 or less, the probability that two cistrons differ at two or more nucleotide sites is less than 10 percent of the heterozygosity, whereas this probability may be as high as 50 percent of the heterozygosity if the heterozygosity is 0.5. A simple estimate for the mean number (d) of site differences between cistrons is d = h/(1 - h) where h is the heterozygosity. At equilibrium, the probability that two cistrons differ by more than one site is equal to h  2, the square of heterozygosity.





Genetics ◽  
1997 ◽  
Vol 146 (4) ◽  
pp. 1489-1499 ◽  
Author(s):  
Yun-Xin Fu

A coalescent theory for a sample of DNA sequences from a partially selfing diploid population and an algorithm for simulating such samples are developed in this article. Approximate formulas are given for the expectation and the variance of the number of segregating sites in a sample of k sequences from n individuals. Several new estimators of the important parameters θ = 4Nμ and the selfing rate s, where N and μ are, respectively, the effective population size and the mutation rate per sequence per generation, are proposed and their sampling properties are studied.



2018 ◽  
Author(s):  
A.P. Jason de Koning ◽  
Bianca D. De Sanctis

AbstractOne of the most fundamental rules of molecular evolution is that the rate of neutral evolution equals the mutation rate and is independent of effective population size. This result lies at the heart of the Neutral Theory, and is the basis for numerous analytic approaches that are widely applied to infer the action of natural selection across the genome and through time, and for dating divergence events using the molecular clock. However, this result was derived under the assumption that evolution is strongly mutation-limited, and it has not been known whether it generalizes across the range of mutation pressures or the spectrum of mutation types observed in natural populations. Validated by both simulations and exact computational analyses, we present a direct and transparent theoretical analysis of the Wright-Fisher model of population genetics, which shows that some of the most important rules of molecular evolution are fundamentally changed by considering recurrent mutation’s full effect. Surprisingly, the rate of the neutral molecular clock is found to have population-size dependence and to not equal the mutation rate in general. This is because, for increasing values of the population mutation rate parameter (θ), the time spent waiting for mutations quickly becomes smaller than the cumulative time mutants spend segregating before a substitution, resulting in a net deceleration compared to classical theory that depends on the population mutation rate. Furthermore, selection exacerbates this effect such that more adaptive alleles experience a greater deceleration than less adaptive alleles, introducing systematic bias in a wide variety of methods for inferring the strength and direction of natural selection from across-species sequence comparisons. Critically, the classical weak mutation approximation performs well only when θ< 0.1, a threshold that many biological populations seem to exceed.



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