Neutral Drift Research Articles

Pervasive Induction of Regulatory Mutation Microclones in Sun-exposed Skin.

Carcinogen-induced mutations are thought near-random, with rare cancer-driver mutations underlying clonal expansion. Using high-fidelity Duplex Sequencing to reach a mutation frequency sensitivity of 4×10 -9 per nt, we report that sun exposure creates pervasive mutations at sites with ∼100-fold UV-sensitivity in RNA-processing gene promoters - cyclobutane pyrimidine dimer (CPD) hyperhotspots - and these mutations have a mini-driver clonal expansion phenotype. Numerically, human skin harbored 10-fold more genuine mutations than previously reported, with neonatal skin containing 90,000 per cell; UV signature mutations increased 8,000-fold in sun-exposed skin, averaging 3×10 -5 per nt. Clonal expansion by neutral drift or passenger formation was nil. Tumor suppressor gene hotspots reached variant allele frequency 0.1-10% via 30-3,000 fold clonal expansion, in occasional biopsies. CPD hyperhotspots reached those frequencies in every biopsy, with modest clonal expansion. In vitro, tumor hotspot mutations arose occasionally over weeks of chronic low-dose exposure, whereas CPD hyperhotspot mutations arose in days at 1000-fold higher frequencies, growing exponentially. UV targeted mini-drivers in every skin cell.

Evolution of the substrate specificity of an RNA ligase ribozyme from phosphorimidazole to triphosphate activation

The acquisition of new RNA functions through evolutionary processes was essential for the diversification of RNA-based primordial biology and its subsequent transition to modern biology. However, the mechanisms by which RNAs access new functions remain unclear. Do RNA enzymes need completely new folds to support new but related functions, or is reoptimization of the active site sufficient? What are the roles of neutral and adaptive mutations in evolutionary innovation? Here, we address these questions experimentally by focusing on the evolution of substrate specificity in RNA-catalyzed RNA assembly. We use directed in vitro evolution to show that a ligase ribozyme that uses prebiotically relevant 5'-phosphorimidazole-activated substrates can be evolved to catalyze ligation with substrates that are 5'-activated with the biologically relevant triphosphate group. Interestingly, despite catalyzing a related reaction, the new ribozyme folds into a completely new structure and exhibits promiscuity by catalyzing RNA ligation with both triphosphate and phosphorimidazole-activated substrates. Although distinct in sequence and structure, the parent phosphorimidazolide ligase and the evolved triphosphate ligase ribozymes can be connected by a series of point mutations where the intermediate sequences retain at least some ligase activity. The existence of a quasi-neutral pathway between these distinct ligase ribozymes suggests that neutral drift is sufficient to enable the acquisition of new substrate specificity, thereby providing opportunities for subsequent adaptive optimization. The transition from RNA-catalyzed RNA assembly using phosphorimidazole-activated substrates to triphosphate-activated substrates may have foreshadowed the later evolution of the protein enzymes that use monomeric triphosphates (nucleoside triphosphates, NTPs) for RNA synthesis.

Cost Optimisation of Individual-Based Institutional Reward Incentives for Promoting Cooperation in Finite Populations

In this paper, we study the problem of cost optimisation of individual-based institutional incentives (reward, punishment, and hybrid) for guaranteeing a certain minimal level of cooperative behaviour in a well-mixed, finite population. In this scheme, the individuals in the population interact via cooperation dilemmas (Donation Game or Public Goods Game) in which institutional reward is carried out only if cooperation is not abundant enough (i.e., the number of cooperators is below a threshold 1≤t≤N-1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$1\\le t\\le N-1$$\\end{document}, where N is the population size); and similarly, institutional punishment is carried out only when defection is too abundant. We study analytically the cases t=1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$t=1$$\\end{document} for the reward incentive under the small mutation limit assumption and two different initial states, showing that the cost function is always non-decreasing. We derive the neutral drift and strong selection limits when the intensity of selection tends to zero and infinity, respectively. We numerically investigate the problem for other values of t and for population dynamics with arbitrary mutation rates.

Inference of chromosome selection parameters and missegregation rate in cancer from DNA-sequencing data

Aneuploidy is frequently observed in cancers and has been linked to poor patient outcome. Analysis of aneuploidy in DNA-sequencing (DNA-seq) data necessitates untangling the effects of the Copy Number Aberration (CNA) occurrence rates and the selection coefficients that act upon the resulting karyotypes. We introduce a parameter inference algorithm that takes advantage of both bulk and single-cell DNA-seq cohorts. The method is based on Approximate Bayesian Computation (ABC) and utilizes CINner, our recently introduced simulation algorithm of chromosomal instability in cancer. We examine three groups of statistics to summarize the data in the ABC routine: (A) Copy Number-based measures, (B) phylogeny tip statistics, and (C) phylogeny balance indices. Using these statistics, our method can recover both the CNA probabilities and selection parameters from ground truth data, and performs well even for data cohorts of relatively small sizes. We find that only statistics in groups A and C are well-suited for identifying CNA probabilities, and only group A carries the signals for estimating selection parameters. Moreover, the low number of CNA events at large scale compared to cell counts in single-cell samples means that statistics in group B cannot be estimated accurately using phylogeny reconstruction algorithms at the chromosome level. As data from both bulk and single-cell DNA-sequencing techniques becomes increasingly available, our inference framework promises to facilitate the analysis of distinct cancer types, differentiation between selection and neutral drift, and prediction of cancer clonal dynamics.

Asian Mus musculus: subspecies divergence, genetic diversity, and historical biogeography

Abstract The House Mouse, Mus musculus, is a model organism that has greatly contributed to evolutionary research. Despite its significance, there remain gaps in our understanding of its phylogeography and population genetic structure in Asian regions. This comprehensive study aims to elucidate the evolutionary history, genetic diversity, and distribution patterns of M. musculus. A diverse data set of 281 M. musculus samples was collected from across Asia, covering 101 localities in 19 countries. Phylogenetic analysis using Cytochrome b and D-Loop region unveiled well-supported lineages. These lineages correspond to: M. m. musculus, M. m. domesticus, M. m. castaneus, and M. m. bactrianus. Also, validity of M. m. bactrianus was questioned. The analysis suggests a monophyletic origin of these subspecies approximately 0.59 million years ago (Mya), followed by 2 main lineages—one consisting of M. m. domesticus (~0.59 Mya) and the other comprising M. m. castaneus, M. m. bactrianus, and M. m. musculus (~0.56 Mya). Genetic diversity varied among subspecies, with M. m. domesticus exhibiting the highest diversity due to its extensive global distribution and M. m. bactrianus exhibiting the lowest diversity due to restriction in southwest Asia. Pairwise genetic distances and Fst values confirmed significant genetic differentiation among the subspecies, underlining their historical isolation. Additionally, a Mantel test indicated that geographical distance played a pivotal role in shaping genetic differentiation. Demographic analysis revealed evidence of population expansions in M. m. domesticus, M. m. musculus, and M. m. castaneus, while M. m. bactrianus showed characteristics of neutral selection and genetic drift. Species distribution modeling, assessing both Current Conditions and the Last Glacial Maximum, indicated habitat shifts and losses during glacial periods, particularly in the eastern and northern regions of Asia. However, each subspecies displayed unique responses to climatic changes, reflecting their distinct ecological adaptations. Historical biogeography analysis pointed to complex origins and a network of dispersal and vicariance events that led to the contemporary distribution of subspecies. Deserts and xeric shrublands emerged as critical areas for diversification and speciation. This study contributes to our understanding of the phylogeography and population genetics of M. musculus in Asia, highlighting the significance of geographical factors and climatic fluctuations in shaping its evolutionary history and genetic diversity.

A transit-amplifying progenitor with biphasic behavior contributes to epidermal renewal.

Transit-amplifying (TA) cells are progenitors that undergo an amplification phase followed by transition into an extinction phase. A long postulated epidermal TA progenitor with biphasic behavior has not yet been experimentally observed in vivo. Here, we identify such a TA population using clonal analysis of Aspm-CreER genetic cell-marking in mice, which uncovers contribution to both homeostasis and injury repair of adult skin. This TA population is more frequently dividing than a Dlx1-CreER-marked long-term self-renewing (e.g. stem cell) population. Newly developed generalized birth-death modeling of long-term lineage tracing data shows that both TA progenitors and stem cells display neutral competition, but only the stem cells display neutral drift. The quantitative evolution of a nascent TA cell and its direct descendants shows that TA progenitors indeed amplify the basal layer before transition and that the homeostatic TA population is mostly in extinction phase. This model will be broadly useful for analyzing progenitors whose behavior changes with their clone age. This work identifies a long-missing class of non-self-renewing biphasic epidermal TA progenitors and has broad implications for understanding tissue renewal mechanisms.

The coalescent in finite populations with arbitrary, fixed structure

The coalescent is a stochastic process representing ancestral lineages in a population undergoing neutral genetic drift. Originally defined for a well-mixed population, the coalescent has been adapted in various ways to accommodate spatial, age, and class structure, along with other features of real-world populations. To further extend the range of population structures to which coalescent theory applies, we formulate a coalescent process for a broad class of neutral drift models with arbitrary – but fixed – spatial, age, sex, and class structure, haploid or diploid genetics, and any fixed mating pattern. Here, the coalescent is represented as a random sequence of mappings C=Ctt=0∞ from a finite set G to itself. The set G represents the “sites” (in individuals, in particular locations and/or classes) at which these alleles can live. The state of the coalescent, Ct:G→G, maps each site g∈G to the site containing g’s ancestor, t time-steps into the past. Using this representation, we define and analyze coalescence time, coalescence branch length, mutations prior to coalescence, and stationary probabilities of identity-by-descent and identity-by-state. For low mutation, we provide a recipe for computing identity-by-descent and identity-by-state probabilities via the coalescent. Applying our results to a diploid population with arbitrary sex ratio r, we find that measures of genetic dissimilarity, among any set of sites, are scaled by 4r(1−r) relative to the even sex ratio case.

Rapid vertebrate speciation via isolation, bottlenecks, and drift

Speciation is often driven by selective processes like those associated with viability, mate choice, or local adaptation, and "speciation genes" have been identified in many eukaryotic lineages. In contrast, neutral processes are rarely considered as the primary drivers of speciation, especially over short evolutionary timeframes. Here, we describe a rapid vertebrate speciation event driven primarily by genetic drift. The White Sands pupfish (Cyprinodon tularosa) is endemic to New Mexico's Tularosa Basin where the species is currently managed as two Evolutionarily significant units (ESUs) and is of international conservation concern (Endangered). Whole-genome resequencing data from each ESU showed remarkably high and uniform levels of differentiation across the entire genome (global FST ≈ 0.40). Despite inhabiting ecologically dissimilar springs and streams, our whole-genome analysis revealed no discrete islands of divergence indicative of strong selection, even when we focused on an array of candidate genes. Demographic modeling of the joint allele frequency spectrum indicates the two ESUs split only ~4 to 5 kya and that both ESUs have undergone major bottlenecks within the last 2.5 millennia. Our results indicate the genome-wide disparities between the two ESUs are not driven by divergent selection but by neutral drift due to small population sizes, geographic isolation, and repeated bottlenecks. While rapid speciation is often driven by natural or sexual selection, here we show that isolation and drift have led to speciation within a few thousand generations. We discuss these evolutionary insights in light of the conservation management challenges they pose.

Imprints of ecological processes in the taxonomic core community: an analysis of naturally replicated microbial communities enclosed in oil.

It is widely assumed that a taxonomic core community emerges among microbial communities from similar habitats because similar environments select for the same taxa bearing the same traits. Yet, a core community itself is no indicator of selection because it may also arise from dispersal and neutral drift, i.e. by chance. Here, we hypothesize that a core community produced by either selection or chance processes should be distinguishable. While dispersal and drift should produce core communities with similar relative taxon abundances, especially when the proportional core community, i.e. the sum of the relative abundances of the core taxa, is large, selection may produce variable relative abundances. We analyzed the core community of 16S rRNA gene sequences of 193 microbial communities occurring in tiny water droplets enclosed in heavy oil from the Pitch Lake, Trinidad and Tobago. These communities revealed highly variable relative abundances along with a large proportional core community (68.0 ± 19.9%). A dispersal-drift null model predicted a negative relationship of proportional core community and compositional variability along a range of dispersal probabilities and was largely inconsistent with the observed data, suggesting a major role of selection for shaping the water droplet communities in the Pitch Lake.

Intercontinental dispersal and niche fidelity drive 50 million years of global diversification in Vertigo land snails

AbstractAimWe aimed to understand how biogeographical processes and moisture niche ecology contributed to the spatio‐temporal diversification dynamics in the land snail genus Vertigo.LocationGlobal (North America, Europe, Asia, Africa).Time PeriodCenozoic era.Major Taxa StudiedMinute terrestrial snails of the genus Vertigo.MethodsWe reconstructed a time‐calibrated phylogeny of 94 Vertigo taxa (~85% of all known extant species) based on mitochondrial and nuclear DNA data. Leveraging this phylogeny with distributional and ecological data from >7000 populations, we performed biogeographic and ecological modelling to investigate evolutionary mechanisms of global Vertigo diversification.ResultsVertigo has diversified since the Early Eocene, ca. 47.6 Ma (95% HPD = 46.0–52.7), with its six subgenera originating from the Late Eocene (30.2–48.7 Ma) to the Early Miocene (13.3–23.0 Ma). Species diversity accumulated linearly, with a slight increase 35–30 and 25–20 Ma, coinciding with the emergence of most subgenera and northern hemisphere cooling, respectively. Biogeographic modelling indicated that most diversification events occurred in sympatry (no range modification), but that rare founder events drove global diversification. Soil moisture conditions, a major variable defining Vertigo niches, displayed significant phylogenetic signal, but varied less among subgenera relative to within. Shifts in biogeographical ranges and moisture niches (or the absence thereof) were significantly associated at macroevolutionary scales, with most niche shifts upon sympatric cladogenesis and hardly any upon founder‐event speciation.Main ConclusionsOur results indicate that ecological shifts in soil moisture niches occasionally drove cladogenesis in sympatry and anagenetic range extensions, but that long‐distance dispersal was mainly successful in the absence of such shifts. A combination of neutral (founder events and drift) and selective mechanisms (adaptive habitat shifts) has determined the macroevolutionary success of Vertigo. Our results imply that species with high niche fidelity or fewer opportunities for long‐distance dispersal will be more vulnerable to future anthropogenic stressors.

Contrasting patterns of sequence variation in steelhead populations reflect distinct evolutionary processes.

Multiple evolutionary processes influence genome-wide allele frequencies and quantifying effects of genetic drift, and multiple forms of selection remain challenging in natural populations. Here, we investigate variation at major effect loci in contrast to patterns of neutral drift across a wide collection of steelhead (Oncorhynchus mykiss) populations that have declined in abundance due to anthropogenic impacts. Whole-genome resequencing of 74 populations of steelhead revealed genome-wide patterns (~8 million SNPs) consistent with expected neutral population structure. However, allelic variation at major effect loci associated with adult migration timing (chromosome 28: GREB1L/ROCK1) and age at maturity (chromosome 25: SIX6) reflected how selection has acted on phenotypic variation in contrast with neutral structure. Variation at major effect loci was influenced by evolutionary processes with differing signals between the strongly divergent Coastal and Inland lineages, while allele frequencies within and among populations within the Inland lineage have been driven by local natural selection as well as recent anthropogenic influences. Recent anthropogenic effects appeared to have influenced the frequency of major effect alleles including artificial selection for specific traits in hatchery stocks with subsequent gene flow into natural populations. Selection from environmental factors at various scales has also likely influenced variation for major effect alleles. These results reveal evolutionary mechanisms that influence allele frequencies at major effect loci that are critical for conservation of phenotypic traits and life history variation of this protected species.

Cost optimisation of hybrid institutional incentives for promoting cooperation in finite populations

In this paper, we rigorously study the problem of cost optimisation of hybrid (mixed) institutional incentives, which are a plan of actions involving the use of reward and punishment by an external decision-maker, for maximising the level (or guaranteeing at least a certain level) of cooperative behaviour in a well-mixed, finite population of self-regarding individuals who interact via cooperation dilemmas (Donation Game or Public Goods Game). We show that a mixed incentive scheme can offer a more cost-efficient approach for providing incentives while ensuring the same level or standard of cooperation in the long-run. We establish the asymptotic behaviour (namely neutral drift, strong selection, and infinite-population limits). We prove the existence of a phase transition, obtaining the critical threshold of the strength of selection at which the monotonicity of the cost function changes and providing an algorithm for finding the optimal value of the individual incentive cost. Our analytical results are illustrated with numerical investigations. Overall, our analysis provides novel theoretical insights into the design of cost-efficient institutional incentive mechanisms for promoting the evolution of cooperation in stochastic systems.

Plants are the drivers of geographic variation of floral odours in brood site pollination mutualisms: A case study of Ficus hirta

Plant odours are central for pollinator attraction. This is particularly true in obligate brood site pollination mutualisms. However, we know little about the evolution of olfactory signalling in these mutualisms. Here, we investigate geographic variation of floral odour in the obligate host-specific brood site pollination mutualism between Ficus hirta and its specialised pollinators. Floral scent samples from nine locations in China were collected using head-space adsorption and were analysed by gas chromatography-mass spectrometry. We evidence progressive geographic divergence of floral odours. The pattern of variation fits plant genetic structure for neutral genes but differs from pollinating insect structuring into species and populations. In our study system, the geographic variation of receptive floral odour presents a pattern that is not distinguishable from neutral drift. The variation is not canalised by the insects. We propose that this pattern characterises obligate brood site pollination mutualisms in which pollinators are host specific and dispersal of plant and insect is limited. Insects with their short generation times and large population sizes rapidly track any chance variation in host receptive inflorescence odours. Plants are the drivers and insects the followers. The source of the geographic variation in floral odours can be genetic or phenotypic in response to local conditions. Strict sense plant-insect co-evolution is not involved. In contrast, previous results on another Ficus-pollinating wasp association suggest that stabilising selection could be at work in more dispersive systems.

Evolutionary dynamics on sequential temporal networks.

Population structure is a well-known catalyst for the evolution of cooperation and has traditionally been considered to be static in the course of evolution. Conversely, real-world populations, such as microbiome communities and online social networks, frequently show a progression from tiny, active groups to huge, stable communities, which is insufficient to be captured by constant structures. Here, we propose sequential temporal networks to characterize growing networked populations, and we extend the theory of evolutionary games to these temporal networks with arbitrary structures and growth rules. We derive analytical rules under which a sequential temporal network has a higher fixation probability for cooperation than its static counterpart. Under neutral drift, the rule is simply a function of the increment of nodes and edges in each time step. But if the selection is weak, the rule is related to coalescence times on networks. In this case, we propose a mean-field approximation to calculate fixation probabilities and critical benefit-to-cost ratios with lower calculation complexity. Numerical simulations in empirical datasets also prove the cooperation-promoting effect of population growth. Our research stresses the significance of population growth in the real world and provides a high-accuracy approximation approach for analyzing the evolution in real-life systems.

Analysis of neutral mutational drift in an allosteric enzyme.

Neutral mutational drift is an important source of biological diversity that remains underexploited in fundamental studies of protein biophysics. This study uses a synthetic transcriptional circuit to study neutral drift in protein tyrosine phosphatase 1B (PTP1B), a mammalian signaling enzyme for which conformational changes are rate limiting. Kinetic assays of purified mutants indicate that catalytic activity, rather than thermodynamic stability, guides enrichment under neutral drift, where neutral or mildly activating mutations can mitigate the effects of deleterious ones. In general, mutants show a moderate activity-stability tradeoff, an indication that minor improvements in the activity of PTP1B do not require concomitant losses in its stability. Multiplexed sequencing of large mutant pools suggests that substitutions at allosterically influential sites are purged under biological selection, which enriches for mutations located outside of the active site. Findings indicate that the positional dependence of neutral mutations within drifting populations can reveal the presence ofallosteric networks and illustrate an approach for using synthetic transcriptional systems to explore these mutations in regulatory enzymes.

The Neutral Theory (Theory of Genetic Drift) and the Nearly Neutral Theory of Molecular Evolution are Opposite to Evolution

The Neutral theory (also known as the theory of genetic drift) means genetic drift and vice-versa. But the Nearly Neutral theory means genetic drift plus natural selection. However, genetic drift changes the gene frequency randomly and thus it is non-additive, directionless and thus valueless for evolution. Again, genetic drift works only in small populations and thus, genetic drift means small population. But small populations have to inbreed and produce homozygous organisms. Consequently, those populations suffer from various diseases and abnormalities and finally may suddenly extinct. Moreover, any homozygous organism means zero variation, mutation-genetic drift equilibrium also creates zero variation. But variation is the raw material of evolution; so, no evolution occurs by the genetic drift. So, evolutionary biologists rejected both the genetic drift and the small populations for any kind of evolution. Hence, the Neutral theory is opposite to any kind of evolution. Again, recent experiments of ecological genetics with small populations, 12 biochemical tests, and the data of the DNA sequence, fossil evidence oppose the Neutral theory. Furthermore, the rate of evolution by the Neutral theory is equal to the rate of mutation. But mutations are opposite to any kind of evolution. So, biologists rejected the Neutral theory. As the natural selection is not justified in Nearly Neutral theory; so, Neutral theory=Nearly Neutral theory. Consequently, the rejection of the Neutral theory means the rejection of the Nearly Neutral theory. Thus, both the Neutral theory and the Nearly Neutral theory are opposite to any kind of evolution.

Evolution of affinity between p53 transactivation domain and MDM2 across the animal kingdom demonstrates high plasticity of motif-mediated interactions.

The interaction between the transcription factor p53 and the ubiquitin ligase MDM2 results in the degradation of p53 and is well-studied in cancer biology and drug development. Available sequence data suggest that both p53 and MDM2-family proteins are present across the animal kingdom. However, the interacting regions are missing in some animal groups, and it is not clear whether MDM2 interacts with, and regulates p53 in all species. We used phylogenetic analyses and biophysical measurements to examine the evolution of affinity between the interacting protein regions: a conserved 12-residue intrinsically disordered binding motif in the p53 transactivation domain (TAD) and the folded SWIB domain of MDM2. The affinity varied significantly across the animal kingdom. The p53TAD/MDM2 interaction among jawed vertebrates displayed high affinity, in particular for chicken and human proteins (KD around 0.1 μM). The affinity of the bay mussel p53TAD/MDM2 complex was lower (KD = 15 μM) and those from a placozoan, an arthropod, and a jawless vertebrate were very low or non-detectable (KD > 100 μM). Binding experiments with reconstructed ancestral p53TAD/MDM2 variants suggested that a micromolar affinity interaction was present in the ancestral bilaterian animal and was later enhanced in tetrapods while lost in other linages. The different evolutionary trajectories of p53TAD/MDM2 affinity during speciation demonstrate high plasticity of motif-mediated interactions and the potential for rapid adaptation of p53 regulation during times of change. Neutral drift in unconstrained disordered regions may underlie the plasticity and explain the observed low sequence conservation in TADs such as p53TAD.

Accessible versatility underpins the deep evolution of plant specialized metabolism

AbstractThe evolution of several hallmark traits of land plants is underpinned by phytochemical innovations. The specialized metabolism of plants can appear like a teeming chaos that has yielded an ungraspable array of chemodiversity. Yet, this diversity is the result of evolutionary processes including neutral evolution, drift, and selection that have shaped the metabolomic networks. Deciphering the evolutionary history of the specialized metabolome in the context of plant terrestrialization has only just begun. Studies on phytochemistry of model organisms and crop plants enabled the sketch of a blueprint for the biochemical landscape of land plants and a good idea on the diversity that can be explored. Evolutionary metabolomics has in the past been successfully used to identify traits that were critical for domestication of angiosperms or to unravel key innovations in land plants. Owing to recent advances in the study of non-model land plants and their close streptophyte algal relatives we can now begin to appreciate the variation of metabolic networks across the green lineage—and understand convergent solutions to similar environmental challenges and effects that plant terrestrialization had on these networks. Here, we highlight the significant progress made with regard to identifying metabolomic diversity by adding non-model organisms to the equation. We discuss the role of neutral evolution in the context of metabolomic diversity and the effects that environmental challenges had on the lineage-specific specialized metabolism from an evolutionary point of view.

How asymmetric mating patterns affect the rate of neutral genetic substitution

IntroductionA population under neutral drift is expected to accumulate genetic substitutions at a fixed “molecular clock” rate over time. If the population is well-mixed, a classic result equates the rate of substitution per generation to the probability of mutation per birth. However, this substitution rate can be altered if individual birth and death rates vary by class or by spatial location.MethodsHere we investigate how mating patterns affect the rate of neutral genetic substitution in a diploid, sexually reproducing population. We employ a general mathematical modeling framework that allows for arbitrary mating pattern and spatial structure.ResultsWe demonstrate that if survival rates and mating opportunities vary systematically across individuals, the rate of neutral substitution can be either accelerated or slowed. In particular, this can occur in populations with uneven sex ratio at birth, or with reproductive skew.DiscussionOur results suggest that estimates of the rate of neutral substitution, in species with uneven sex ratio and/or reproductive skew, may need to take asymmetries in mating opportunity and survival into account.

Both selection and drift drive the spatial pattern of adaptive genetic variation in a wild mammal

The major histocompatibility complex (MHC) has been intensively studied for the relative effects of different evolutionary forces in recent decades. Pathogen-mediated balancing selection is generally thought to explain the high polymorphism observed in MHC genes, but it is still unclear to what extent MHC diversity is shaped by selection relative to neutral drift. In this study, we genotyped MHC class II DRB genes and 15 neutral microsatellite loci across 26 geographic populations of European badgers (Meles meles) covering most of their geographic range. By comparing variation of microsatellite and diversity of MHC at different levels, we demonstrate that both balancing selection and drift have shaped the evolution of MHC genes. When only MHC allelic identity was investigated, the spatial pattern of MHC variation was similar to that of microsatellites. By contrast, when functional aspects of the MHC diversity (e.g., immunological supertypes) were considered, balancing selection appears to decrease genetic structuring across populations. Our comprehensive sampling and analytical approach enable us to conclude that the likely mechanisms of selection are heterozygote advantage and/or rare-allele advantage. This study is a clear demonstration of how both balancing selection and genetic drift simultaneously affect the evolution of MHC genes in a widely distributed wild mammal.