Biology subjects

Innan, H.

Publications and source records attributed to Innan, H..

12 recordsLinked to original sources

bioRxiv2026

Spontaneous Emergence and Turnover of the Sex-Determining Locus

Anisogamy is nearly universal across multicellular organisms, yet how two discrete sexes arise in genomes with many recombining autosomal loci remains unresolved. Classic models show that disruptive selection on gamete size can drive anisogamy, but their single-locus assumptions conflict with empirical evidence that sexual differentiation typically involves numerous autosomal genes whose linkage is continuously broken by recombination. Here we develop an evolutionary model of gene regulatory networks (GRNs) to show that disruptive selection favoring complementary mating phenotypes can spontaneously generate a bistable developmental architecture producing two stable sexual phenotypes, together with a master sex-determining locus that biases development toward one or the other. Once such a bistable GRN evolves, the identity of the master regulator becomes flexible, enabling turnover of sex-determining loci without disrupting sexual differentiation. Our results provide a general mechanism for the origin, robustness, and evolutionary lability of sex-determination systems, linking classical gamete-level selection with the emergence of developmental bistability through the evolution of GRNs.

evolutionary biology↗

bioRxiv2025

Coexistence of piRNA and KZFP Defense Systems: Evolutionary Dynamics of Layered Defense against Transposable Elements

Transposable elements (TEs) pose a persistent threat to genome stability, and host organisms have consequently evolved sophisticated defense mechanisms to restrain them. In animals, the most prominent systems include PIWI-interacting RNAs (piRNAs) and Kruppel-associated box zinc-finger proteins (KZFPs). Because both systems recognize TEs in a sequence-specific manner and induce epigenetic silencing, they appear functionally redundant at first glance. However, KZFPs are a relatively recent innovation that emerged and diversified in genomes where the piRNA pathway was already established. This raises an important question: under what conditions can a second, seemingly redundant defense system invade and persist? To address this, we constructed a mathematical model integrating the evolutionary dynamics of TEs, piRNAs, and KZFPs. Our approach focuses on a key mechanistic asymmetry between the two defense systems: whereas piRNA-mediated suppression is dependent on TE activity, KZFPs provide constitutive suppression that does not rely on ongoing TE activity. We show that these distinct modes of action generate interactions that extend beyond simple redundancy or additivity. We derive analytical conditions under which KZFPs can invade a pre-existing TE-piRNA equilibrium and characterize the evolutionary logic that enables stable coexistence of these multilayered defense strategies. Together, our results provide a theoretical framework for understanding how complex, layered genome defense systems can evolve and persist.

evolutionary biology↗

bioRxiv2022

A Novel Bacterial Speciation Process Observed in a Symbiotic Marine Population

Incomplete lineage sorting (ILS), where ancestral polymorphisms persist through rapid speciation, is a hallmark of eukaryotic radiations but undocumented in prokaryotes. We report ILS associated speciation in the globally distributed marine bacterium Sulfitobacter, analyzing 74 strains from 16 oceanic regions and 15 ecosystem types. Genomic analysis resolved over ten genetically monomorphic clades sharing near uniform whole genome divergence (average nucleotide identity {approx}95%). However, individual genes and even adjacent nucleotide sites support conflicting phylogenetic relationships among clades. The median length of nearly identical sequence blocks supporting alternative topologies is less than 50 base pairs, far shorter than typical adaptive cassettes. This within gene, site level discordance provides a diagnostic signature of ancestral polymorphism retention following rapid fragmentation, ruling out adaptive gene sweeps. Demographic inference places this radiation on a timescale of tens of millennia, 100 to 1,000 fold faster than eukaryotic ILS, and traces the clades to a hyper polymorphic, highly recombining ancestor. Neutral simulations show that transient mutation surges or population bottlenecks alone can generate this pattern, without adaptive selection or ecological partitioning. By bridging eukaryotic and prokaryotic speciation paradigms, our findings demonstrate that ILS, previously considered exclusive to sexual eukaryotes, can drive rapid, neutral diversification in bacteria, expanding the mechanisms known to generate prokaryotic biodiversity.

microbiology↗

bioRxiv2020

Establishment of a new sex-determining allele driven by sexually antagonistic selection

Some species undergo frequent turnovers of sex-determining locus, rather than having stable diverged sex chromosomes. In such species, how often turnover occurs is a fundamental evolutionary question. We model the process with considering a linked locus under sexually antagonistic selection. The entire process of a turnover may be divided into two phases, which are referred to as the stochastic and deterministic phases. The stochastic phase is when a new sex-determining allele just arises and is still rare and random genetic drift plays an important role. In the deterministic phase, the new allele further increases in frequency by positive selection. The theoretical results currently available are for the deterministic phase, which demonstrated that a turnover of a newly arisen sex determining locus could benefit from selection at a linked locus under sexually antagonistic selection, by assuming that sexually antagonistic selection works in a form of balancing selection. In this work, we provide a comprehensive theoretical description of the entire process from the stochastic phase to the deterministic phase. In addition to balancing selection, we explore several other modes of selection on the linked locus. Our theory allows us make a quantitative argument on the rate of turnover and the effect of the mode of selection at the linked locus. We also performed simulations to explore the pattern of polymorphism around the new sex determining locus. We find that the pattern of polymorphism is informative to infer how selection worked through the turnover process.

evolutionary biology↗

bioRxiv2020

Genome analyses reveal the hybrid origin of the staple food crop white Guinea yam

White Guinea yam (Dioscorea rotundata) is an important staple tuber crop of West Africa. However, its origin remains unclear. In this study, we re-sequenced 336 accessions of white Guinea yam and compared them with the sequences of the wild Dioscorea species using an improved reference genome sequence of D. rotundata. Our results suggest a hybrid origin of white Guinea yam from crosses between the rainforest wild species D. praehensilis and the savannah-adapted D. abyssinica. We identified a higher genomic contribution from D. abyssinica in the sex chromosome of Guinea yam and an extensive introgression around the SWEETIE gene. Our findings point to a complex domestication scenario for Guinea yam and highlight the importance of wild species as gene donors for improvement of this crop through molecular breeding.

evolutionary biology↗

bioRxiv2020

High-performance pipeline for MutMap and QTL-seq

Bulked segregant analysis implemented in MutMap and QTL-seq is a powerful and efficient method to identify agronomically important loci. However, the previous pipelines were not user-friendly to install and run. Here, we describe new pipelines for MutMap and QTL-seq. These updated pipelines are approximately 5-8 times faster than the previous pipeline, are easier for novice users to use and can be easily installed through bioconda with all dependencies.

bioinformatics↗

bioRxiv2019

Establishment Process of a Magic Trait Allele subject to Both Divergent Selection and Assortative Mating

Sexual selection and divergent selection are among the major driving forces of reproductive isolation, which could eventually result in speciation. A magic trait is defined such that a single trait is subject to both divergent selection and sexual selection through phenotype-based assortative mating. We are here interested in the evolutionary behavior of alleles in a genetic locus responsible for a magic trait. We assume that, in a pair of homogeneous subpopulations, a mutant allele arises at the magic trait locus, and theoretically obtain the probability that the new allele establishes in the population. We also consider the trajectory of allele frequency along the establishment. Divergent selection simply favors the new allele to fix where it is beneficial, whereas assortative mating works against rare alleles. It is theoretically demonstrated that the fate of the new allele is determined by the relative contributions of the two selective forces, divergent selection and assortative mating, when the allele is rare so that the two selective forces counteract. We also show that random genetic drift also plays an important role. The theoretical results would contribute to improve our understanding of how natural selection initiates speciation.

evolutionary biology↗

bioRxiv2019

Theoretical Expression for the Evolution of Genomic Island of Speciation: From Its Birth to Preservation

Ecological speciation could be driven by divergent selection that works to maintain phenotypes that are adaptive to each niche. In its early stages, genetic divergence (or FST) can be maintained around the target sites of divergent selection, while in other regions, genetic variation can be mixed by gene flow or migration. Such regions of elevated genetic divergence are called genomic islands of speciation. In this work, we theoretically consider the evolutionary process of a genomic island of speciation, from its birth to stable preservation. Under a simple two-population model, we use a diffusion approach to obtain analytical expressions for the probability of initial establishment of a locally adaptive allele, the reduction of genetic variation due to the spread of the adaptive allele, and the process to the development of a sharp peak of divergence. Our result would be useful to understand how genomes evolve through ecological speciation with gene flow.

evolutionary biology↗

bioRxiv2018

Muller’s ratchet as a mechanism of frailty and multimorbidity

Mutation accumulation has been proposed as a cause of senescence. In this process, both constitutional and recurrent mutations accumulate gradually and differentially among differentiating cells, tissues and organs, in relation to stage and age, analogous to Mullers ratchet in asexually reproducing organisms. Latent and cascading deleterious effects of mutations might initiate steady \"accumulation of deficits\" in cells, leading to cellular senescence, and functional decline of tissues and organs, and ultimately manifest as frailties and disease. We investigated a few of these aspects in cell populations through modeling and simulation using the Moran birth-death process, under varied scenarios of mutation accumulation. Our results agree with the principle of Mullers ratchet. The ratchet speed in a given tissue depends on the population size of cells, mutation rate, and selection coefficient. Additionally, deleterious mutations seem to rapidly accumulate particularly early in the life-course, during which the rate of cell division is high, thereby exerting a greater effect on cellular senescence. The speed of the ratchet afterward varies greatly between cells nested in tissues and tissues within organs due to heterogeneity in the life span and turnover rate of specific cell types. Importantly, the ratchet accelerates with age, resulting in a synergistic fitness decay in cell populations. We extend Fishers average excess concept and rank order scale to interpret differential phenotypic effects of mutation load in a given tissue. We conclude that classical evolutionary genetic models could explain partially, the origins of frailty, subclinical conditions, morbidity and health consequences of senescence.\n\nSignificanceFrailty is defined as physiological and functional decline of organs and organ systems, due to deficit accumulation from stochastic damages within the organism with advanced age. Equivalently, with age, both constitutional and somatic mutations accumulate gradually and differentially among cells, cell lineages, tissues, and organs. Since most mutations are deleterious, accumulation of random and recurrent mutations could create a \"load,\" on the genome and contextually express in the epigenome and phenotype spaces. Here we extend Mullers ratchet principle to explain frailty and multi-morbidity using the Moran model and simulations. Our results agree with the Mullers ratchet principle. We emphasize the need for considering cumulative effects of the entire spectrum of mutations for explaining the origin of frailty, sub-clinical conditions, and morbidity.

genetics↗

bioRxiv2017

The coalescent for prokaryotes with homologous recombination from external source

The coalescent process for prokaryote species is theoretically considered. Prokaryotes undergo homologous recombination not only with other individuals within the same species (intra-specific recombination) but also with other species (inter-specific recombination). This work particularly focuses the latter because the former has been well incorporated in the framework of the coalescent. We here developed a simulation framework for generating patterns of SNPs (single nucleotide polymorphisms) allowing integration of external DNA out of the focal species, and a simulator named msPro was developed. We found that the joint work of intra- and inter-specific recombination creates a complex pattern of SNPs. The direct effect of inter-specific recombination is to increase the amount of polymorphism. Because inter-specific recombination is very rare in general, it creates a regions with an exceptionally high level of polymorphisms. Following an inter-specific recombination event, intra-specific recombination chop the integrated foreign DNA into small pieces, making a complicated pattern of SNPs that looks as if foreign DNAs were integrated multiple times. This work with the msPro simulator would be useful to understand and evaluate the relative contribution of intra- and inter specific recombination to creating complicated patterns of SNPs in prokaryotes.

evolutionary biology↗

bioRxiv2017

Simulation Framework for Generating Intratumor Heterogeneity Patterns in a Cancer Cell Population

As cancer cell populations evolve, they accumulate a number of somatic mutations, resulting in heterogeneous subclones in the final tumor. Understanding the mechanisms that produce intratumor heterogeneity (ITH) is important for selecting the best treatment. Although some studies have involved ITH simulations, their model settings differed substantially. Thus, only limited conditions were explored in each. Herein, we developed a general framework for simulating ITH patterns and a simulator (tumopp). Tumopp offers many setting options so that simulations can be carried out under various settings. Setting options include how the cell division rate is determined, how daughter cells are placed, and how driver mutations are treated. Furthermore, to account for the cell cycle, we introduced a gamma function for the waiting time involved in cell division. Tumopp also allows simulations in a hexagonal lattice, in addition to a regular lattice that has been used in previous simulation studies. A hexagonal lattice produces a more biologically reasonable space than a regular lattice. Using tumopp, we investigated how model settings affect the growth curve and ITH pattern. It was found that, even under neutrality (with no driver mutations), tumopp produced dramatically variable patterns of ITH and tumor morphology, from tumors in which cells with different genetic background are well intermixed to irregular shapes of tumors with a cluster of closely related cells. This result suggests a caveat in analyzing ITH data with simulations with limited settings, and tumopp will be useful to explore ITH patterns in various conditions.\n\nAuthor SummaryUnderstanding the mechanisms that produce intratumor heterogeneity (ITH) is important for selecting the best treatment. Despite a growing body of data and tools for analyzing ITH, the spatial structure and its evolution are poorly understood because of the lack of well established theoretical framework. Herein, we provide a general framework for simulating ITH patterns, under which a simulator (tumopp) is developed. Tumopp offers many setting options so that simulations can be carried out under various settings. Simulations using tumopp demonstrate that dramatically variable patterns of ITH and tumor morphology can be produced depending on the model setting. The present work provides a guideline for future simulation studies of cancer cell populations.

cancer biology↗

bioRxiv2017

Allele Frequency Spectrum in a Cancer Cell Population

A cancer grows from a single cell, thereby constituting a large cell population. In this work, we are interested in how mutations accumulate in a cancer cell population. We provided a theoretical framework of the stochastic process in a cancer cell population and obtained near exact expressions of allele frequency spectrum or AFS (only continuous approximation is involved) from both forward and backward treatments under a simple setting; all cells undergo cell division and die at constant rates, b and d, respectively, such that the entire population grows exponentially. This setting means that once a parental cancer cell is established, in the following growth phase, all mutations are assumed to have no effect on b or d (i.e., neutral or passengers). Our theoretical results show that the difference from organismal population genetics is mainly in the coalescent time scale, and the mutation rate is defined per cell division, not per time unit (e.g., generation). Except for these two factors, the basic logic are very similar between organismal and cancer population genetics, indicating that a number of well established theories of organismal population genetics could be translated to cancer population genetics with simple modifications.

cancer biology↗