Biology subjects

Rosenberg, N. A.

Publications and source records attributed to Rosenberg, N. A..

At least 19 recordsLinked to original sources

bioRxiv2025

Coalescent theory of the {psi} directionality index

The{psi} directionality index was introduced by Peter & Slatkin (Evolution 67: 3274-3289, 2013) to infer the direction of range expansions from single-nucleotide polymorphism variation. Computed from the joint site frequency spectrum for two populations,{psi} uses shared genetic variants to measure the difference in the amount of genetic drift experienced by the populations, associating excess drift with greater distance from the origin of the range expansion. Although{psi} has been successfully applied in natural populations, its statistical properties have not been well understood. In this paper, we define {Psi} as a random variable originating from a coalescent process in a two-population demography. For samples consisting of a pair of diploid genomes, one from each of two populations, we derive expressions for moments [E] [{Psi}k] for standard parameterizations of bottlenecks during a founder event. For the expectation [E][{Psi}], we identify parameter combinations that represent distinct demographic scenarios yet yield the same value of [E][{Psi}]. We also show that the variance [V][{Psi}] increases with the time since the bottleneck and bottleneck severity, but does not depend on the size of the ancestral population; the ancestral population size affects{psi} computed from many biallelic loci only through its contribution to the total number of loci available for the computation. Finally, we analyze the values of [E][{Psi}] computed from existing demographic models of Drosophila melanogaster and compare them with empirically computed{psi} . Our work builds the foundation for theoretical treatments of the{psi} index and can help in evaluating its behavior in empirical applications. SummaryThe statistic known as the "directionality index" examines variants shared between two populations with a goal of identifying which population has experienced a greater amount of genetic drift. This study develops theoretical predictions for the directionality index in coalescent models of pairs of populations descended from a common ancestral population. It determines the influence of bottlenecks, population growth, and population sizes on the directionality index. In Drosophila melanogaster, patterns in genomic data accord with the direction of the model predictions, with{psi} suggesting a higher level of drift in European than in African populations.

genetics↗

bioRxiv2024

Using mathematical constraints to explain narrow ranges for allele-sharing dissimilarities

Allele-sharing dissimilarity (ASD) statistics are measures of genetic differentiation for pairs of individuals or populations. Given the allele-frequency distributions of two populations--possibly the same population--the expected value of an ASD statistic is computed by evaluating the expectation of the pairwise dissimilarity between two individuals drawn at random, each from its associated allele-frequency distribution. For each of two ASD statistics, which we term [D]1 and [D]2, we investigate the extent to which the expected ASD is constrained by allele frequencies in the two populations; in other words, how is the magnitude of the measure bounded as a function of the frequency of the most frequent allelic type? We first consider dissimilarity of a population with itself, obtaining bounds on expected ASD in terms of the frequency of the most frequent allelic type in the population. We then examine pairs of populations that might or might not possess the same most frequent allelic type. Across the unit interval for the frequency of the most frequent allelic type, the expected allele-sharing dissimilarity has a range that is more restricted than the r0, 1s interval. The mathematical constraints on expected ASD assist in explaining a pattern observed empirically in human populations, namely that when averaging across loci, allele-sharing dissimilarities between pairs of individuals often tend to vary only within a relatively narrow range.

genetics↗

bioRxiv2024

Quantifying compositional variability in microbial communities with FAVA

Microbial communities vary across space, time, and individual hosts, presenting new challenges for the development of statistics measuring the variability of community composition. To understand differences across microbiome samples from different host individuals, sampling times, spatial locations, or experimental replicates, we present FAVA, a new normalized measure for characterizing compositional variability across multiple microbiome samples. FAVA quantifies variability across many samples of taxonomic or functional relative abundances in a single index ranging between 0 and 1, equaling 0 when all samples are identical and equaling 1 when each sample is entirely comprised of a single taxon. Its definition relies on the population-genetic statistic FST, with samples playing the role of "populations" and taxa playing the role of "alleles." Its convenient mathematical properties allow users to compare disparate data sets. For example, FAVA values are commensurable across different numbers of taxonomic categories and different numbers of samples considered. We introduce extensions that incorporate phylogenetic similarity among taxa and spatial or temporal distances between samples. We illustrate how FAVA can be used to describe across-individual taxonomic variability in ruminant microbiomes at different regions along the gastrointestinal tract. In a second example, a longitudinal analysis of gut microbiomes of healthy human adults taking an antibiotic, we use FAVA to quantify the increase in temporal variability of microbiomes following the antibiotic course and to measure the duration of the antibiotics influence on microbial variability. We have implemented this tool in an R package, FAVA, which can fit easily into existing pipelines for the analysis of microbial relative abundances. Significance statementStudies of microbial community composition across time, space, or biological replicates often rely on summary statistics that analyze just one or two samples at a time. Although these statistics effectively summarize the diversity of one sample or the compositional dissimilarity between two samples, they are ill-suited for measuring variability across many samples at once. Measuring compositional variability among many samples is key to understanding the temporal stability of a community across multiple time points, or the heterogeneity of microbiome composition across multiple experimental replicates or host individuals. Our proposed measure, FAVA, meets the need for a statistic summarizing compositional variability across many microbiome samples all at once.

ecology↗

bioRxiv2023

Prolonged delays in human microbiota transmission after a controlled antibiotic perturbation

Humans constantly encounter new microbes, but few become long-term residents of the adult gut microbiome. Classical theories predict that colonization is determined by the availability of open niches, but it remains unclear whether other ecological barriers limit commensal colonization in natural settings. To disentangle these effects, we used a controlled perturbation with the antibiotic ciprofloxacin to investigate the dynamics of gut microbiome transmission in 22 households of healthy, cohabiting adults. Colonization was rare in three-quarters of antibiotic-taking subjects, whose resident strains rapidly recovered in the week after antibiotics ended. In contrast, the remaining antibiotic-taking subjects exhibited lasting responses, with extensive species losses and transient expansions of potential opportunistic pathogens. These subjects experienced elevated rates of commensal colonization, but only after long delays: many new colonizers underwent sudden, correlated expansions months after the antibiotic perturbation. Furthermore, strains that had previously transmitted between cohabiting partners rarely recolonized after antibiotic disruptions, showing that colonization displays substantial historical contingency. This work demonstrates that there remain substantial ecological barriers to colonization even after major microbiome disruptions, suggesting that dispersal interactions and priority effects limit the pace of community change.

microbiology↗

bioRxiv2023

Bijections between the multifurcating unlabeled rooted trees and the positive integers

AO_SCPLOWBSTRACTC_SCPLOWColijn and Plazzotta (Systematic Biology 67:113-126, 2018) described a bijective scheme for associating the unlabeled bifurcating rooted trees with the positive integers. In mathematical and biological applications of unlabeled rooted trees, however, nodes of rooted trees are sometimes multifurcating rather than bifurcating. Building on the bijection between the unlabeled bifurcating rooted trees and the positive integers, we describe bijective schemes for associating the unlabeled multifurcating rooted trees with the positive integers. We devise bijections with the positive integers for a set of trees in which each non-leaf node has exactly k child nodes, and for a set of trees in which each non-leaf node has at most k child nodes. The calculations make use of Macaulays binomial expansion formula. The generalization to multifurcating trees can assist with the use of unlabeled trees for applications in evolutionary biology, such as the measurement of phylogenetic patterns of genetic lineages in pathogens. Mathematics subject classification (2020)05C05, 05C30, 92D15

evolutionary biology↗

bioRxiv2022

Record-matching of STR profiles with fragmentary genomic SNP data

In many forensic settings, identity of a DNA sample is sought from poor-quality DNA, for which the typical STR loci tabulated in forensic databases are not possible to reliably genotype. Genome-wide SNPs, however, can potentially be genotyped from such samples via next-generation sequencing, so that queries can in principle compare SNP genotypes from DNA samples of interest to STR genotype profiles that represent proposed matches. We use genetic record-matching to evaluate the possibility of testing SNP profiles obtained from poor-quality DNA samples to identify exact and relatedness matches to STR profiles. Using 2,504 whole-genome sequences, we show that in some settings, similar match accuracies to those seen with full coverage of the genome are obtained by genetic record-matching for SNP data that represent 5-10% genomic coverage. Thus, if even a fraction of random genomic SNPs can be genotyped by next-generation sequencing, then the potential may exist to test the resulting genotype profiles for matches to profiles consisting exclusively of nonoverlapping STR loci. The result has implications in relation to criminal justice, mass disasters, missing-person cases, studies of ancient DNA, and genomic privacy.

genetics↗

bioRxiv2022

On a mathematical connection between single-elimination sports tournaments and evolutionary trees

How many ways are there to arrange the sequence of games in a single-elimination sports tournament? We consider the connection between this enumeration problem and the enumeration of "labeled histories," or sequences of asynchronous branching events, in mathematical phylogenetics. The possibility of playing multiple games simultaneously in different arenas suggests an extension of the enumeration of labeled histories to scenarios in which multiple branching events occur simultaneously. We provide a recursive result enumerating game sequences and labeled histories in which simultaneity is allowed. For a March Madness basketball tournament of 68 labeled teams, the number of possible sequences of games is ~ 1.91 x 1078 if arbitrarily many arenas are available, but only ~ 3.60 x 1068 if all games must be played sequentially on the same arena.

evolutionary biology↗

bioRxiv2022

Limiting distribution of X-chromosomal coalescence times under first-cousin consanguineous mating

By providing additional opportunities for coalescence within families, the presence of consanguineous unions in a population reduces coalescence times relative to non-consanguineous populations. First-cousin consanguinity can take one of six forms differing in the configuration of sexes in the pedigree of the male and female cousins who join in a consanguineous union: patrilateral parallel, patrilateral cross, matrilateral parallel, matrilateral cross, bilateral parallel, and bilateral cross. Considering populations with each of the six types of first-cousin consanguinity individually and a population with a mixture of the four unilateral types, we examine coalescent models of consanguinity. We previously computed, for first-cousin consanguinity models, the mean coalescence time for X-chromosomal loci and the limiting distribution of coalescence times for autosomal loci. Here, we use the separation-of-time-scales approach to obtain the limiting distribution of coalescence times for X-chromosomal loci. This limiting distribution has an instantaneous coalescence probability that depends on the probability that a union is consanguineous; lineages that do not coalesce instantaneously coalesce according to an exponential distribution. We study the effects on the coalescence time distribution of the type of first-cousin consanguinity, showing that patrilateral-parallel and patrilateral-cross consanguinity have no effect on X-chromosomal coalescence time distributions and that matrilateral-parallel consanguinity decreases coalescence times to a greater extent than does matrilateral-cross consanguinity.

genetics↗

bioRxiv2022

The admixture histories of Cabo Verde

From the 15th to the 19th century, the Trans-Atlantic Slave-Trade (TAST) influenced the genetic and cultural diversity of numerous populations. We explore genomic and linguistic data from the nine islands of Cabo Verde, the earliest European colony of the era in Africa, a major Slave-Trade platform between the 16th and 19th centuries, and a previously uninhabited location ideal for investigating early admixture events between Europeans and Africans. Using local-ancestry inference approaches, we find that genetic admixture in Cabo Verde occurred primarily between Iberian and certain Senegambian populations, although forced and voluntary migrations to the archipelago involved numerous other populations. Inter-individual genetic and linguistic variation recapitulates the geographic distribution of individuals birth-places across Cabo Verdean islands, following an isolation-by-distance model with reduced genetic and linguistic effective dispersals within the archipelago, and suggesting that Kriolu language variants have developed together with genetic divergences at very reduced geographical scales. Furthermore, based on approximate bayesian computation inferences of highly complex admixture histories, we find that admixture occurred early on each island, long before the 18th-century massive TAST deportations triggered by the expansion of the plantation economy in Africa and the Americas, and after this era mostly during the abolition of the TAST and of slavery in European colonial empires. Our results illustrate how shifting socio-cultural relationships between enslaved and non-enslaved communities during and after the TAST, shaped enslaved-African descendants genomic diversity and structure on both sides of the Atlantic.

genetics↗

bioRxiv2022

Approximations to the expectations and variances of ratios of tree properties under the coalescent

Properties of gene genealogies such as tree height (H), total branch length (L), total lengths of external (E) and internal (I) branches, mean length of basal branches (B), and the underlying coalescence times (T) can be used to study population-genetic processes and to develop statistical tests of population-genetic models. Uses of tree features in statistical tests often rely on predictions that depend on pairwise relationships among such features. For genealogies under the coalescent, we provide exact expressions for Taylor approximations to expected values and variances of ratios Xn/Yn, for all 15 pairs among the variables {Hn, Ln, En, In, Bn, Tk}, considering n leaves and 2 [≤] k [≤] n. For expected values of the ratios, the approximations match closely with empirical simulation-based values. The approximations to the variances are not as accurate, but they generally match simulations in their trends as n increases. Although En has expectation 2 and Hn has expectation 2 in the limit as n [->] {infty}, the approximation to the limiting expectation for En/Hn is not 1, instead equaling{pi} 2/3 - 2 {approx} 1.28987. The new approximations augment fundamental results in coalescent theory on the shapes of genealogical trees.

genetics↗

bioRxiv2021

The probability of joint monophyly of all species in an arbitrary species tree.

Monophyly is a feature of a set of genetic lineages in which every lineage in the set is more closely related to all other members of the set than it is to any lineage outside the set. Multiple sets of lineages that are separately monophyletic are said to be reciprocally monophyletic, or jointly monophyletic. The prevalence of reciprocal monophyly, or joint monophyly, has been used to evaluate phylogenetic and phylogeographic hypotheses, as well as to delimit species. These applications often make use of a probability of joint monophyly under models of gene lineage evolution. Studies in coalescent theory have computed this joint monophyly probability for small numbers of separate groups in arbitrary species trees, and for arbitrary numbers of separate groups in trivial species trees. Here, generalizing existing results on monophyly probabilities under the multispecies coalescent, we derive the probability of joint monophyly for arbitrary numbers of separate groups in arbitrary species trees. We illustrate how our result collapses to previously examined cases. We also study the effect of tree height, sample size, and number of species on the probability of joint monophyly. The result also enables computation of relatively simple lower and upper bounds on the joint monophyly probability. Our results expand the scope of joint monophyly calculations beyond small numbers of species, subsuming past formulas that have been used in simpler cases.

evolutionary biology↗

bioRxiv2021

FSTruct: An Fst-based tool for measuring ancestry variation in inference of population structure

In model-based inference of population structure from individual-level genetic data, individuals are assigned membership coefficients in a series of statistical clusters generated by clustering algorithms. Distinct patterns of variability in membership coefficients can be produced for different groups of individuals, for example, representing different predefined populations, sampling sites, or time periods. Such variability can be difficult to capture in a single numerical value; membership coefficient vectors are multivariate and potentially incommensurable across groups, as the number of clusters over which individuals are distributed can vary among groups of interest. Further, two groups might share few clusters in common, so that membership coefficient vectors are concentrated on different clusters. We introduce a method for measuring the variability of membership coefficients of individuals in a predefined group, making use of an analogy between variability across individuals in membership coefficient vectors and variation across populations in allele frequency vectors. We show that in a model in which membership coefficient vectors in a population follow a Dirichlet distribution, the measure increases linearly with a parameter describing the variance of a specified component of the membership vector. We apply the approach, which makes use of a normalized FST statistic, to data on inferred population structure in three example scenarios. We also introduce a bootstrap test for equivalence of two or more groups in their level of membership coefficient variability. Our methods are implemented in the R package FSTruct.

evolutionary biology↗

bioRxiv2021

Mathematical constraints on FST: multiallelic markers in arbitrarily many populations

Interpretations of values of the FST measure of genetic differentiation rely on an understanding of its mathematical constraints. Previously, it has been shown that FST values computed from a biallelic locus in a set of multiple populations and FST values computed from a multiallelic locus in a pair of populations are mathematically constrained as a function of the frequency of the allele that is most frequent across populations. We generalize from these cases to report here the mathematical constraint on FST given the frequency M of the most frequent allele at a multiallelic locus in a set of multiple populations. Using coalescent simulations of an island model of migration with an infinitely-many-alleles mutation model, we argue that the joint distribution of FST and M helps in disentangling the separate influences of mutation and migration on FST. Finally, we show that our results explain a puzzling pattern of microsatellite differentiation: the lower FST in an interspecific comparison between humans and chimpanzees than in the comparison of chimpanzee populations. We discuss the implications of our results for the use of FST.

genetics↗

bioRxiv2020

Variance and limiting distribution of coalescence times in a diploid model of a consanguineous population

Recent modeling studies interested in runs of homozygosity (ROH) and identity by descent (IBD) have sought to connect these properties of genomic sharing to pairwise coalescence times. Here, we examine a variety of features of pairwise coalescence times in models that consider consanguinity. In particular, we extend a recent diploid analysis of mean coalescence times for lineage pairs within and between individuals in a consanguineous population to derive the variance of coalescence times, studying its dependence on the frequency of consanguinity and the kinship coefficient of consanguineous relationships. We also introduce a separation-of-time-scales approach that treats consanguinity models analogously to mathematically similar phenomena such as partial selfing, using this approach to obtain coalescence-time distributions. This approach shows that the consanguinity model behaves similarly to a standard coalescent, scaling population size by a factor 1 − 3c, where c represents the kinship coefficient of a randomly chosen mating pair. It provides the explanation for an earlier result describing mean coalescence time in the consanguinity model in terms of c. The results extend the potential to make predictions about ROH and IBD in relation to demographic parameters of diploid populations.Competing Interest StatementThe authors have declared no competing interest.View Full Text

genetics↗

bioRxiv2020

On the Colijn-Plazzotta numbering scheme for unlabeled binary rooted trees

Colijn & Plazzotta (Syst. Biol. 67:113-126, 2018) introduced a scheme for bijectively associating the unlabeled binary rooted trees with the positive integers. First, the rank 1 is associated with the 1-leaf tree. Proceeding recursively, ordered pair (k1, k2), k1 [>=] k2 [>=] 1, is then associated with the tree whose left subtree has rank k1 and whose right subtree has rank k2. Following dictionary order on ordered pairs, the tree whose left and right subtrees have the ordered pair of ranks (k1, k2) is assigned rank k1(k1 - 1)/2 + 1 + k2. With this ranking, given a number of leaves n, we determine recursions for an, the smallest rank assigned to some tree with n leaves, and bn, the largest rank assigned to some tree with n leaves. For n equal to a power of 2, the value of an is seen to increase exponentially with 2n for a constant {approx} 1.24602; more generally, we show it is bounded an < 1.5n. The value of bn is seen to increase with [Formula] for a constant {beta} {approx} 1.05653. The great difference in the rates of increase for an and bn indicates that as the index v is incremented, the number of leaves for the tree associated with rank v quickly traverses a wide range of values. We interpret the results in relation to applications in evolutionary biology. Mathematics subject classification05C05, 92B10, 92D15

evolutionary biology↗

bioRxiv2020

Human-Genetic Ancestry Inference and False Positives in Forensic Familial Searching

In forensic familial search methods, a query DNA profile is tested against a database to determine if the query profile represents a close relative of a database entrant. One challenge for familial search is that the calculations may require specification of allele frequencies for the unknown population from which the query profile has originated. Allele-frequency misspecification can substantially inflate false-positive rates compared to use of allele frequencies drawn from the same population as the query profile. Here, we use ancestry inference on the query profile to circumvent the high false-positive rates that result from highly misspecified allele frequencies. In particular, we perform ancestry inference on the query profile and make use of allele frequencies based on its inferred genetic ancestry. In a test for sibling matches on profiles that represent unrelated individuals, we demonstrate that false-positive rates for familial search with use of ancestry inference to specify the allele frequencies are similar to those seen when allele frequencies align with the population of origin of a profile. Because ancestry inference is possible to perform on query profiles, the extreme allele-frequency misspecifications that produce the highest false-positive rates can be avoided. We discuss the implications of the results in the context of concerns about the forensic use of familial searching.

genetics↗

bioRxiv2020

Genetic Adaptation in New York City Rats

Brown rats (Rattus norvegicus) thrive in urban environments by navigating the anthropocentric environment and taking advantage of human resources and by-products. From the human perspective, rats are a chronic problem that causes billions of dollars in damage to agriculture, health and infrastructure. Did genetic adaptation play a role in the spread of rats in cities? To approach this question, we collected whole-genome sequences from 29 brown rats from New York City (NYC) and scanned for genetic signatures of adaptation. We tested for (i) high-frequency, extended haplotypes that could indicate selective sweeps and (ii) loci of extreme genetic differentiation between the NYC sample and a sample from the presumed ancestral range of brown rats in northeast China. We found candidate selective sweeps near or inside genes associated with metabolism, diet, the nervous system and locomotory behavior. Patterns of differentiation between NYC and Chinese rats at putative sweep loci suggests that many sweeps began after the split from the ancestral population. Together, our results suggest several hypotheses on adaptation in rats living in close proximity to humans.

evolutionary biology↗

bioRxiv2019

A Metric Space of Ranked Tree Shapes and Ranked Genealogies

Genealogical tree modeling is essential for estimating evolutionary parameters in population genetics and phylogenetics. Recent mathematical results concerning ranked genealogies without leaf labels enable new opportunities in the analysis of evolutionary trees. In particular, comparisons between ranked genealogies facilitate the study of evolutionary processes for organisms sampled in multiple time periods. We propose a metric space on ranked genealogies for lineages sampled from both isochronous and time-stamped heterochronous sampling. Our new tree metrics make it possible to conduct statistical analyses of ranked tree shapes and timed ranked tree shapes, or ranked genealogies. Such analyses allow us to assess differences in tree distributions, quantify estimation uncertainty, and summarize tree distributions. We show the utility of our metrics via simulations and an application in infectious diseases.

evolutionary biology↗