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Stochastic information processing biological systems.

We propose a simple, biochemically-based model for stochastic information processing in brain, genetic, and, consequently, evolutionary modelling. The essential features of reaction-diffusion processes are realized by intrinsically stochastic probabilistic automata (Shannon and Weaver, 1948; see also Ashby, 1958, von Neumann, 1966; Burks, 1970; Paz, 1971) whose definition extends that of classical automata. (Classical automata are deterministic; earlier work on probabilistic automata focused on error correction and at least approximating deterministic behavior.) We call these probabilistic automata biochemical to emphasize the role of intrinsically stochastic process in biological information processing. Our model yields descriptions of gradualism (Conrad, 1974), learning, and apparent inefficiencies in the brain, and partially resolves the near impossibility of simultaneous point mutations (Conrad, 1972, 1978) in genetics. The genetic model implies an evolutionary dynamics of punctuated equilibria (Gould and Eldredge, 1977).

Animals

Lineage-specific adaptation and resistance in Candida albicans.

Candida albicans exhibits substantial phenotypic and ecological diversity; however, the exact relationship between its population structure, adaptation to specific niches, and antifungal resistance remains incompletely understood. To investigate these evolutionary dynamics, we analyzed the whole-genome sequences from 591 publicly available isolates, integrating nuclear and mitochondrial phylogenomics with ecological and resistance-associated genomic analyses. Phylogenomic analyses resolved 18 core nuclear clusters together with multiple admixed lineages. Strong cytonuclear concordance was noted in the majority of the central lineages, contrasting with a higher discordance among the admixed groups, consistent with recurrent genetic exchange. The analysis revealed that geographic origin explains a larger fraction of genetic variance than anatomical niche, supporting a predominantly generalist population structure. A notable exception was Cluster N16 (Candida africana), which presented a strict genital origin in our dataset (n = 34). Additionally, although the mitochondrial genome exhibits strong purifying selection, candidate residues under diversifying selection correlated with specific niches (e.g., bloodstream) have been identified. Analysis of five resistance-associated genes (ERG11, UPC2, FKS1, TAC1 and FUR1) revealed that resistance-associated variants were generally rare but exhibited distinct gene-specific patterns. In case of ERG11 and FUR1 they were concentrated in a specific clade (N11, N17, and their admixed Group A) and exhibit gene-dependent zygosity patterns. In summary, the evolution of C. albicans appears to be driven by a predominantly clonal model punctuated by episodic genetic exchange, where both ecological adaptation and antifungal resistance mutations exhibit genomic signatures marked by lineage specificity.

Antifungal resistance

Fe-S cluster deficiency drives small colony variant formation in persistent infections.

INTRODUCTION: Small colony variants (SCVs) of Staphylococcus aureus (S. aureus) are associated with persistent infections and poor clinical outcomes. The mechanisms driving stable SCV formation remain poorly understood, particularly concerning metabolic adaptations. This study explores the in-host evolutionary dynamics of S. aureus and identifies a novel genetic determinant linked to SCV formation. OBJECTIVES: To investigate the genetic mutations and phenotypic adaptations underlying SCV formation, with a focus on the role of a novel mutation in the sufB gene, which is critical for Fe-S cluster biosynthesis. METHODS: Sequential isolates from a patient with recurrent infections were analyzed using whole-genome sequencing, antimicrobial susceptibility testing, and functional assays. The phylogenetic relationship of the isolates was determined, and specific mutations were identified. Functional assays included aconitase and glutamate synthase activity measurements, ATP level quantification, reactive oxygen species (ROS) production, and biofilm formation assays. In vivo pathogenesis was assessed using a murine catheter infection model. RESULTS: A novel frameshift mutation in sufB was identified, disrupting Fe-S cluster biosynthesis and impairing the TCA cycle and electron transport chain, leading to reduced ATP and ROS production. This metabolic reprogramming promoted stable SCV formation, characterized by slow growth, enhanced tolerance to antibiotics and neutrophil-mediated killing, and persistent inflammation in vivo. Restoration of sufB reversed these phenotypes, confirming its pivotal role in SCV-associated persistence. CONCLUSION: sufB is a novel genetic determinant of stable SCV formation through Fe-S cluster deficiency, driving metabolic shifts that enhance immune evasion and chronic infection. Our findings highlight antibiotic stewardship and suggest potential therapeutic strategies for managing persistent SCV-associated infections.

Staphylococcus aureus

Genomic mechanism of aroma terpenoids biosynthesis in plants.

BACKGROUND: Aroma terpenoids are crucial plant secondary metabolites with physiological and commercial importance. Interestingly, both closely and distantly related species can synthesize identical aroma terpenoids. With the development of genome sequencing technology, it has become possible to elucidate the genomic mechanism underlying this phenomenon. AIM: This review highlights whole-genome data as a robust strategy for investigating the genomic mechanism of aroma terpenoids biosynthesis in plants, and provides new perspectives on the origin, evolution, and engineering of terpene synthases (TPSs). This aims to significantly benefit plant breeding and enhance suitability for industrial production. KEY SCIENTIFIC CONCEPTS OF REVIEW: Genomic mechanism of aroma terpenoids biosynthesis in plant genomes is the genetic and evolutionary dynamics. We elaborate the genomic mechanism governing the biosynthesis of plant-derived aroma terpenoids in three dimensions: (1) Genome-wide identification and phylogenetic analyses of TPSs. The same aroma terpenoids were produced by numerous plant species with chromosome-level genomes. Based on 34 plant genomes, we identified 1643 TPSs and classified them into seven subfamilies. (2) Functional and structural basis of TPSs. We found that TPSs with identical functions in distant species exhibit low sequence similarity but conserved active cavity architectures. Conversely, functionally distinct TPSs in closely related species cluster phylogenetically but differ in active cavity structures. (3) Patterns of TPS gene origination. Comparative genomic analyses within and between species revealed three patterns enabling TPSs to acquire the same functions: tandem duplications, dispersed duplications, and genes without duplication.

Terpenes

Convergence and global molecular epidemiology of Klebsiella pneumoniae plasmids harbouring the iuc3 virulence locus: a population genomic analysis.

BACKGROUND: Klebsiella pneumoniae is an important pathogen of humans and animals. In the past five years, increasing reports of convergent strains that carry both virulence factors and antimicrobial resistance genes (ARGs) have raised serious public health concerns. The aim of this study is to describe the global diversity of plasmids carrying iuc3 (a key virulence factor in K pneumoniae associated with pigs and clinical isolates) from diverse settings, and their role in the emergence of convergent strains through hybridisation with plasmids carrying ARGs. METHODS: This population genomic analysis study was designed to describe both the global and local diversity of iuc3-carrying plasmids from diverse sources, and the co-occurrence of iuc3 with ARGs. We used all 4148 Klebsiella spp isolates from two large One-Health studies (SpARK, Italy, and OH-DART, Thailand), including 191 Klebsiella isolates from pigs, 635 from clinical isolates, 1040 from hospital and community carriage, and 2282 from other sources. Short-read sequencing of Klebsiella isolates was performed as part of the SpARK study. We sequenced Klebsiella isolates from the OH-DART (MicrobesNG, Birmingham, UK; HiSeq and NovaSeq, Illumina San Diego, CA, USA; GridION, Oxford Nanopore Technologies, Oxford, UK) and SpARK (MinION or GridION, Oxford Nanopore Technologies, Oxford, UK) studies. We also retrieved plasmid sequences carrying iuc3 from the National Centre for Biotechnology Information (NCBI). To ascertain the degree of diversity, evolutionary dynamics, and structuring across ecological and geographical axes, we detected ARGs and virulence loci, analysed clustering patterns and generated approximate maximum-likelihood phylogenetic trees. FINDINGS: We identified 48 K pneumoniae isolates with iuc3 in the SpARK data and 79 in the OH-DART data. Three (2·4%) of these 127 isolates were from clinical sources, 73 (57·5%) were from pig or pork meat. iuc3 isolates corresponded to multiple (n=47) host sequence types (STs), with ST35, ST45, ST881, ST25, and ST967 harbouring iuc3 in both datasets. We generated hybrid assemblies for 44 (SpARK) and 36 (OH-DART) isolates, plus a single iuc3 isolate from Germany. 53 (65·4%) of these isolates were from pigs, three (3·7%) from clinical sources, and 25 (30·9%) from other sources. There were an additional 48 iuc3 positive isolates from our collections for which only short read data was available. A single iuc3-positive Klebsiella oxytoca isolate from a pig farm was detected in the SpARK data, which was also sequenced. We identified 330 iuc3-positive isolates and 58 iuc3-carrying plasmid assemblies from NCBI, of which 83 (21·4%) were from clinical sources, 120 from pigs (30·9%), and 185 (47·7%) from other sources or of unknown provenance. These isolates were from K pneumoniae except two isolates of Klebsiella quasipneumoniae subsp similipneumoniae and one of Enterobacter hormaechei. The combined dataset of 517 iuc3 plasmids ranged in size from 110 375 bp to 365 580 bp and mostly corresponded to multiple IncFIB(K) and IncFII replicon types. We found seven convergent K pneumoniae plasmids in the Thai data: six from fresh markets and one from a neighbouring hospital. These plasmids emerged through the hybridisation of cocirculating iuc3 plasmids and plasmids encoding extended-spectrum β-lactamases (ESBLs), although none of these seven plasmids carried genes encoding carbapenemases. We also identified putative cocirculating parental plasmids carrying iuc3 and ESBL-encoding genes. Clustering and phylogenetic analysis resolved the iuc3 plasmid sequences into three groups, which were consistent using both complete plasmid sequences (n=139) and short-read data (n=517). In the complete plasmid sequence data, 66 strains contained group 1 plasmids, 38 strains contained group 2 plasmids, and 35 strains contained group 3 plasmids. Group 3 plasmids are mostly carried by isolates circulating in hospitals throughout Asia, with occasional examples in Europe and elsewhere, and carry multiple ARGs and potential virulence factors. By contrast, group 1 plasmids are commonly carried by porcine isolates in Europe, and group 2 are a heterogeneous mixture of geographical and ecological sources. INTERPRETATION: Plasmid hybridisation occurs frequently outside of the health-care environment and can lead to the convergence of resistance and virulence traits. Generating complete plasmid sequences from regional population-scale samples facilitates the identification of convergent plasmids and their putative parental plasmids. Three robust groups of iuc3 plasmids were resolved, which show both epidemiological and geographical differences; one of these groups was associated with clinical isolates in Asia and warrants targeted plasmid surveillance. FUNDING: UKRI, JPIAMR, Evolution Education Trust, and a Schlumberger Foundation Fellowship.

Plasmids

Molecular characteristics, phylodynamics, and evolutionary changes of avian infectious bronchitis virus detected from chickens in Yunnan Province, 2021-2024.

Avian infectious bronchitis virus (IBV) is endemic in poultry flocks worldwide, posing a significant threat to the global poultry industry. Frequent mixing of free-range local chickens with introduced chickens in Yunnan Province, China, facilitates the transmission, recombination, and mutation of avian IBV, thereby complicating disease prevention and control. In this study, we aimed to investigate the presence of IBV in poultry populations in Yunnan Province. Samples were collected from live poultry markets (LPMs) and breeding farms, comprising 725 randomly sampled cloacal/fecal swabs and 55 tissue samples. IBV-positive samples were confirmed via polymerase chain reaction (PCR), with an overall positivity rate of 0.89% (7/780) for all tested samples. The positivity rate was 0.35% (2/564) in Kunming, 3.7% (2/54) in Zhaotong, 20% (1/5) in Yuxi, and 12.5% (2/16) in Baoshan, while no IBV was detected in samples from Lanping, Xichou, or Ninglang. Six IBV strains, including five GI-19 strains and one GVI-1 strain, were successfully isolated. Phylogenetic analysis further showed that the Yunnan GI-19 strains predominantly clustered with strains originating from Sichuan Province. Sequencing of the S1 gene revealed several amino acids substitutions per isolate in hypervariable regions HVR1-HVR3. Notably, a valine (V) and glycine (G) insertion between amino acid positions 88 and 89 was identified exclusively in isolate F210, a feature rarely reported in IBV. Protein-protein docking analysis indicated that the unique 88-89 insertion in isolate F210 S1 may alter its binding interactions with the host receptor ANPEP. Whole-genome comparison revealed that isolate YX3 shared 97.05% nucleotide identity with strain CK/CH/GX/YL17/2017 from Guangxi, whereas isolates Q47, F13, and F210 shared 96.40%-97.27% identity with strain CK/Henan/H1036/2021 from Henan. Recombination analysis detected obvious recombination events in isolates F13, F210, Q47, and YX3, with GI-22 strains serving as the major parental donors. These genetic characteristics, recombination patterns, and structural insights demonstrate the complex evolutionary dynamics of circulating IBV strains in Yunnan. Continuous molecular epidemiological surveillance combined with functional protein analysis is essential to monitor emerging variants and formulating targeted, effective disease control strategies.

Avian infectious bronchitis virus

Evolutionary principles for general frequency-dependent two-phenotype models in sexual populations.

The evolutionary dynamics in general two-sex two-phenotype frequency-dependent selection models are studied with respect to underlying multi-allele one-locus genetic systems. Two classes of equilibria come into play: genotypic equilibria, with equilibrium allelic frequencies independent of the phenotype, and phenotypic equilibria, which are characterized by equal mean phenotypic fitnesses. The exact conditions for genotypic equilibria to exist and be stable and for phenotypic equilibria to exist and be evolutionarily attractive are examined. Using adequate definitions of mean fitnesses in general contexts of frequency-dependent selection in dioecious populations, we show that two phenotypes, when they can coexist in the population, tend to balance their fitnesses as far as is allowed by the genetic system as more alleles responsible for phenotype determination are introduced into the population.

Alleles

The evolution of mate choice in a fluctuating environment.

This paper analyzes the evolutionary dynamics of a locus controlling the degree of female mating preference in a temporally fluctuating environment. Preference for mating with males with respect to their genotypes at a locus that is subject to temporally varying natural selection pressure is considered first. With weak selection and free recombination between the choice locus and the selected locus, preference for mating with heterozygotes appears to be favored. With strong selection, preference for homozygous mates may be favored. In each case, choice alleles may increase from very low initial frequencies to near fixation, in contrast to previous models of mate choice in varying environments. Linkages between the two loci has complex effects on the strength and direction of selection for mate choice. Preference for mating with males with the currently fitter genotypes at the locus under natural selection is also modelled. Provided that the environmental period is not too short, a rare allele conferring such preference may be favored and spread to fixation. Strong natural selection, tight linkage and a short environmental period may produce polymorphism for the level of mate choice.

Alleles

Free fitness that always increases in evolution.

I here introduce a free fitness function in population biology, which monotonically increases with time and takes its maximum at the evolutionary equilibrium. By suitably defining an "index" for each state, the free fitness is expressed as the average index plus an entropy term. In many cases, the index has a biologically clear meaning, such as the logarithmic population mean fitness. The technique is applicable to any Markov process model (either continuous or discrete) with a positive steady state. I discuss four examples from various branches of population biology: (1) one-locus-two-allele system of population genetics with mutation, selection, and random genetic drift; (2) evolutionary dynamics of quantitative characters; (3) a molecular evolution model; and (4) an ecological succession model. Introducing free fitness clarifies the balance between systematic forces (e.g. natural selection or successional trend toward the climax) and disturbing processes (e.g. random drift).

Animals

Expansion of satellite DNAs derived from transposable elements in beetles with reduced diploid numbers.

Repetitive DNA sequences are ubiquitous in eukaryotic genomes, significantly influencing their structure, function, and evolution. They can facilitate genomic rearrangements, contributing to chromosomal and genomic diversity. Chrysomelidae (Coleoptera) beetles are known for their highly diverse karyotypes and heterochromatin distribution. In this study, we advanced the understanding of the intricate relationship between satellite DNA-like sequences (named here solely as satDNA) and genome organization/reshuffling using three species of Eumolpinae chrysomelids. We investigated the satellitomes of three species with divergent karyotypes that had undergone independent chromosomal fusions: Colaspis laeta (2n = 22, Xyp), with a conserved karyotype; Endocephalus bigatus (2n = 10, neo-XY); and Iphimeis dives (2n = 14, neo-XY). Our comparative analysis revealed highly divergent patterns of satDNA origin, organization, and evolution. In species with reduced chromosome numbers and neo-sex chromosomes, we observed a high abundance of transposable element-related (TE-related) satDNAs. In Colaspis laeta, the sex chromosomes (Xyp) showed an advanced level of differentiation. However, in the species with a reduction in diploid number, such a level of differential enrichment of repetitive DNAs was not observed in the sex chromosomes, indicating an early stage of differentiation. Our findings support the hypothesis that chromosomal rearrangements and reorganization of repetitive DNA sequences are connected, with extensive reshuffling observed in species with reduced diploid numbers. Moreover, the data reinforce the involvement of TEs in satDNA origin, which could spread widely throughout the genome, including euchromatic areas. This study provides new insights into the evolutionary dynamics of repetitive DNAs in non-model species, emphasizing the impact of chromosomal rearrangements on genome architecture and evolution.

Animals

Evolution of DNA methylation in the human brain.

DNA methylation is a critical regulatory mechanism implicated in development, learning, memory, and disease in the human brain. Here we have elucidated DNA methylation changes during recent human brain evolution. We demonstrate dynamic evolutionary trajectories of DNA methylation in cell-type and cytosine-context specific manner. Specifically, DNA methylation in non-CG context, namely CH methylation, has increased (hypermethylation) in neuronal gene bodies during human brain evolution, contributing to human-specific down-regulation of genes and co-expression modules. The effects of CH hypermethylation is particularly pronounced in early development and neuronal subtypes. In contrast, DNA methylation in CG context shows pronounced reduction (hypomethylation) in human brains, notably in cis-regulatory regions, leading to upregulation of downstream genes. We show that the majority of differential CG methylation between neurons and oligodendrocytes originated before the divergence of hominoids and catarrhine monkeys, and harbors strong signal for genetic risk for schizophrenia. Remarkably, a substantial portion of differential CG methylation between neurons and oligodendrocytes emerged in the human lineage since the divergence from the chimpanzee lineage and carries significant genetic risk for schizophrenia. Therefore, recent epigenetic evolution of human cortex has shaped the cellular regulatory landscape and contributed to the increased vulnerability to neuropsychiatric diseases.

Animals

Characterization and evolutionary history of novel SARS-CoV-2-related viruses in bats from Cambodia.

Circulating bat coronaviruses present a significant pandemic threat, yet our understanding of their genetic diversity and evolutionary dynamics remains limited. Over 3 years, we sampled 1,462 bats in Cambodia's Steung Treng province, identifying extensive and diverse coronaviruses co-circulation. Using metatranscriptomic and amplicon sequencing, we generated 33 complete sarbecovirus genomes sequences, revealing novel lineages that cluster into four distinct groups, each associated with different Rhinolophus bat species. Our analysis highlights rapid migration and recombination of sarbecovirus lineages over short distances and timescales. Of note, the receptor-binding domains of two novel viral groups exhibit high similarity to SARS-CoV-2, and pseudovirus assays confirmed the ability of this spike protein to mediate entry into cells expressing human ACE2, suggesting a potential zoonotic risk. The observed genetic diversity underscores the urgent need for continuous surveillance to identify high-risk animal-to-human interfaces and inform pandemic preparedness.

Animals

Widespread horizontal transfer and strong selection enhance microbial adaptation in Antarctic soils.

Terrestrial Antarctica harbors compositionally diverse and functionally distinct microbial life. Yet the eco-evolutionary processes underlying adaptation to Antarctica's polyextreme conditions remain largely unknown. Here, we address how horizontal gene transfer (HGT) and de novo mutations influence microbial adaptation in 16 Antarctic soils using combined short- and long-read datasets. Phylogenetic reconciliation and mobile genetic element analysis of 676 metagenome-assembled genomes show frequent HGT across communities. While transferred genes span diverse functional categories, those involved in energy metabolism are exchanged at higher frequency. Genes for aerotrophy, i.e. the consumption of atmospheric trace gases to provide energy, carbon, and hydration, are among the most frequently disseminated. Approximately a quarter of carbon monoxide dehydrogenases and [NiFe]-hydrogenases are predicted to be horizontally acquired and are often associated with mobile genetic elements. Analysis of polymorphisms suggests widespread purifying selection, particularly for aerotrophy genes, providing further evidence that aerotrophy is critical for microbial survival in Antarctica. Genetic variation in hydrogenases is tightly associated with predicted protein structures, with intense selection acting on critical sites preserving stability and function. Together, these findings show that previously unrecognized eco-evolutionary dynamics shape the composition and function of Antarctic microbial communities, and confirm aerotrophy is a strongly selected and horizontally disseminated trait.

Antarctic Regions

Multiple local PfDHFR I164L haplotype expansions drive Plasmodium falciparum antifolate resistance in Uganda.

Mutations in the Plasmodium falciparum genes, pfdhfr and pfdhps, drive antifolate resistance and threaten malaria control in regions where sulfadoxine-pyrimethamine (SP) is the primary chemoprevention strategy. The spatial patterns and evolutionary dynamics of these mutations in high-transmission settings remain incompletely understood. Here we genotyped 11 resistance-associated mutations in pfdhfr and pfdhps in 4,725 P. falciparum isolates collected from 16 Ugandan health facilities as part of annual surveillance between 2016 and 2022. Notably, we show that the frequency of PfDHFR I164L, which confers higher pyrimethamine resistance, increased over time from 19.4% to 32.4%. Using identity-by-descent, haplotype structure, and extended haplotype homozygosity analyses, we show that PfDHFR I164L is present on multiple haplotype backgrounds and undergoes localised expansions, without detectable signatures of recent positive selection at all but one site. Our results suggest that the evolution of antifolate resistance, driven by PfDHFR I164L, is spatially heterogeneous and complex in regions that primarily use SP chemoprevention programmes.

Plasmodium falciparum

Type 1 interferon perturbates clonal competition by reshaping human blood development.

Inflammation accelerates evolutionary dynamics of hematopoietic stem cells (HSCs) in clonal hematopoiesis and myeloid neoplasms. We studied HSCs, progenitors and immune cells from patients with myeloproliferative neoplasms at baseline and following interferon-α (IFNα) treatment, the only therapy to deplete mutated stem cells. We deployed single-cell multiomics methods that distinguish the IFNα effects on mutated stem cells from the admixed wild-type HSCs, with respect to their differentiation, transcriptomes, immunophenotypes and chromatin accessibility. IFNα simultaneously activated HSCs into two polarized states: a lymphoid progenitor expansion associated with an anti-inflammatory state and an inflammatory myeloid progenitor state derived from HSCs. The augmented lymphoid differentiation balanced the typical myeloproliferative-neoplasm-induced myeloid bias, associated with normalized blood counts. Somatic mutations modified the effects of IFNα on HSC differentiation and cell cycle entry rates. Clonal fitness upon IFNα exposure was due to resistance of CALR- or JAK2-mutated stem cells to differentiate into inflammatory myeloid progenitors.

Journal Article

Evolution of continuous variation: direct approach through joint distribution of genotypes and phenotypes.

The evolutionary dynamics of the joint distribution of genotypes and phenotypes is studied. The model, originally devised to study the joint effects of Mendelian and other types of transmissions, provides results of interest also to the theory of direct Mendelian transmission with natural selection. Assuming bivariate normal distributions, it is shown that in the latter case genotypic and phenotypic means and variances, and genotype-phenotype correlation can be expressed recursively as functions of the parameters for the selection, environmental, and mutation variance. Equilibria and rates of approach for these moments are calculated. It is also proved that in the presence of selection the heritability,defined as the ratio of expected genotypic to expected phenotypic variance after selection, is greater than that before selection by a predictable amount and that it can be greater than unity.

Biological Evolution

Interspecific cytoplasmic gene flow in the absence of nuclear gene flow: evidence from Drosophila.

mtDNA polymorphism has been studied by restriction endonuclease site variation in Drosophila pseudoobscura and its sibling species D. persimilis. Eight enzymes have been used to study 54 isofemale strains from areas where the two species are sympatric and D. pseudoobscura is allopatric. Where sympatric, 75-80% of the strains have mitochondrial genomes found in both species. Where allopatric, D. pseudoobscura has diverged to the point where none of the strains have mtDNA in common with D. persimilis. The most likely explanation for this observation is that where sympatric the two species hybridize frequently enough to keep their mtDNA from diverging. However, hybridization has not prevented their nuclear genomes from diverging, perhaps due to selection against nuclear gene introgression contrasted with little or no selection against mtDNA introgression. These observations suggest that nuclear and cytoplasmic genomes have different evolutionary dynamics.

Animals

Interaction of selection and biased gene conversion in a multigene family.

A model of the evolutionary dynamics of a multigene family in a finite population under the joint effects of selection and (possibly biased) gene conversion is analyzed. It is assumed that the loss or fixation of a polymorphism at any particular locus in the gene family occurs on a much faster time scale than the introduction of new alleles to a monomorphic locus by gene conversion. A general formula for the fixation of a new allele throughout a multigene family for a wide class of selection functions with biased gene conversion is given for this assumption. Analysis for the case of additive selection shows that (i) unless selection is extremely weak or bias is exceptionally strong, selection usually dominates the fixation dynamics, (ii) if selection is very weak, then even a slight conversion bias can greatly alter the fixation probabilities, and (iii) if both selection and conversion bias are sufficiently small, the substitution rate of new alleles throughout a multigene family is approximately the single locus mutation rate, the same result as for neutral alleles at a single-copy gene. Finally, I analyze a fairly general class of underdominant speciation models involving multigene families, concluding for these models under weak conversion that although the probability of fixation may be relatively high, the expected time to fixation is extremely long, so that speciation by "molecular drive" is unlikely. Furthermore, speciation occurs faster by fixing underdominant alleles of the same effect at single-copy genes than by fixing the same number of loci in a single multigene family under the joint effects of selection, conversion, and drift.

Alleles