Evolvability predicts macroevolution under fluctuating selection.

Heritable variation is a prerequisite for evolutionary change, but the relevance of genetic constraints on macroevolutionary timescales is debated. By using two datasets on fossil and contemporary taxa, we show that evolutionary divergence among populations, and to a lesser extent among species, increases with microevolutionary evolvability. We evaluate and reject several hypotheses to explain this relationship and propose that an effect of evolvability on population and species divergence can be explained by the influence of genetic constraints on the ability of populations to track rapid, stationary environmental fluctuations.

Impact of pre-copulatory sexual cannibalism on genetic diversity and efficacy of selection.

Factors that increase reproductive variance among individuals act to reduce effective population size (Ne), which accelerates the loss of genetic diversity and decreases the efficacy of purifying selection. These factors include sexual cannibalism, offspring investment and mating system. Pre-copulatory sexual cannibalism, where the female consumes the male prior to mating, exacerbates this effect. We performed comparative transcriptomics in two spider species, the cannibalistic Trechaleoides biocellata and the non-cannibalistic T. keyserlingi, to generate genomic evidence to support these predictions. First, we estimated heterozygosity and found that genetic diversity is relatively lower in the cannibalistic species. Second, we calculated dN/dS ratios as a measure of purifying selection; a higher dN/dS ratio indicated relaxed purifying selection in the cannibalistic species. These results are consistent with the hypothesis that sexual cannibalism impacts operational sex ratio and demographic processes, which interact with evolutionary forces to shape the genetic structure of populations. However, other factors such as the mating system and life-history traits contribute to shaping Ne. Comparative analyses across multiple contrasting species pairs would be required to disentangle these effects. Our study highlights that extreme behaviours such as pre-copulatory cannibalism may have profound eco-evolutionary effects.

Genome-wide association study and genomic selection of spike-related traits in bread wheat.

KEY MESSAGE: Identification of 337 stable MTAs for wheat spike-related traits improved model accuracy, and favorable alleles of MTA259 and MTA64 increased grain weight and yield per plant. Wheat (Triticum aestivum L.) is one of the three primary global, staple crops. Improving spike-related traits in wheat is crucial for optimizing spike and plant morphology, ultimately leading to increased grain yield. Here, we performed a genome-wide association study using a dataset of 24,889 high-quality unique single-nucleotide polymorphisms (SNPs) and phenotypic data from 314 wheat accessions across eight diverse environments. In total, 337 stable and significant marker-trait associations (MTAs) related to spike-related traits were identified. MTA259 and MTA64 were consistently detected in seven and six environments, respectively. The presence of favorable alleles associated with MTA259 and MTA64 significantly reduced wheat spike exsertion length and spike length, while enhancing thousand kernel weight and yield per plant. Combined gene expression and network analyses identified TraesCS6D03G0692300 and TraesCS6D03G0692700 as candidate genes for MTA259 and TraesCS2D03G0111700 and TraesCS2D03G0112500 for MTA64. The identified MTAs significantly improved the prediction accuracy of each model compared with using all the SNPs, and the random forest model was optimal for genome selection. Additionally, the eight stable and major MTAs, including MTA259, MTA64, MTA66, MTA94, MTA110, MTA165, MTA180, and MTA164, were converted into cost-effective and efficient detection markers. This study provided valuable genetic resources and reliable molecular markers for wheat breeding programs.

Does Behavior Evolve First? Correlated Responses to Selection for Voluntary Wheel-Running Behavior in House Mice.

AbstractHow traits at multiple levels of biological organization evolve in a correlated fashion in response to directional selection is poorly understood, but two popular models are the very general "behavior evolves first" (BEF) hypothesis and the more specific "morphology-performance-behavior-fitness" (MPBF) paradigm. Both acknowledge that selection often acts relatively directly on behavior and that when behavior evolves, other traits will as well but most with some lag. However, this proposition is exceedingly difficult to test in nature. Therefore, we studied correlated responses in the high-runner (HR) mouse selection experiment, in which four replicate lines have been bred for voluntary wheel-running behavior and compared with four nonselected control (C) lines. We analyzed a wide range of traits measured at generations 20-24 (with a focus on new data from generation 22), coinciding with the point at which all HR lines were reaching selection limits (plateaus). Significance levels (226 P values) were compared across trait types by ANOVA, and we used the positive false discovery rate to control for multiple comparisons. This meta-analysis showed that, surprisingly, the measures of performance (including maximal oxygen consumption during forced exercise) showed no evidence of having diverged between the HR and C lines, nor did any of the life history traits (e.g., litter size), whereas body mass had responded (decreased) at least as strongly as wheel running. Overall, results suggest that the HR lines of mice had evolved primarily by changes in motivation rather than performance ability at the time they were reaching selection limits. In addition, neither the BEF model nor the MPBF model of hierarchical evolution provides a particularly good fit to the HR mouse selection experiment.

Characterizing genetic variation on the Z chromosome in Schistosoma japonicum reveals host-parasite co-evolution.

BACKGROUND: Schistosomiasis is a neglected tropical disease that afflicts millions of people worldwide; it is caused by Schistosoma, the only dioecious flukes with ZW systems. Schistosoma japonicum is endemic to Asia; the Z chromosome of S. japonicum comprises one-quarter of the entire genome. Detection of positive selection using resequencing data to understand adaptive evolution has been applied to a variety of pathogens, including S. japonicum. However, the contribution of the Z chromosome to evolution and adaptation is often neglected. METHODS: We obtained 1,077,526 high-quality SNPs on the Z chromosome in 72 S. japonicum using re-sequencing data publicly. To examine the faster Z effect, we compared the sequence divergence of S. japonicum with two closely related species, Schistosoma haematobium and S. mansoni. Genetic diversity was compared between the Z chromosome and autosomes in S. japonicum by calculating the nucleotide diversity (π) and Dxy values. Population structure was also assessed based on PCA and structure analysis. Besides, we employed multiple methods including Tajima's D, FST, iHS, XP-EHH, and CMS to detect positive selection signals on the Z chromosome. Further RNAi knockdown experiments were performed to investigate the potential biological functions of the candidate genes. RESULTS: Our study found that the Z chromosome of S. japonicum showed faster evolution and more pronounced genetic divergence than autosomes, although the effect may be smaller than the variation among genes. Compared with autosomes, the Z chromosome in S. japonicum had a more pronounced genetic divergence of sub-populations. Notably, we identified a set of candidate genes associated with host-parasite co-evolution. In particular, LCAT exhibited significant selection signals within the Taiwan population. Further RNA interference experiments suggested that LCAT is necessary for S. japonicum survival and propagation in the definitive host. In addition, we identified several genes related to the specificity of the intermediate host in the C-M population, including Rab6 and VCP, which are involved in adaptive immune evasion to the host. CONCLUSIONS: Our study provides valuable insights into the adaptive evolution of the Z chromosome in S. japonicum and further advances our understanding of the co-evolution of this medically important parasite and its hosts.

Evolutionarily stable payoff matrix in hawk-dove games.

BACKGROUND: Classical matrix game models aim to find the endpoint of behavioural evolution for a set of fixed possible interaction outcomes. Here, we introduce an evolutionary model in which not only the players' strategies but also the payoff matrix evolves according to natural selection. RESULTS: We start out from the hawk-dove matrix game and, in a way that is consistent with the monomorphic model setup of Maynard Smith and Price, introduce an evolving phenotypic trait that quantifies fighting ability and determines the probability of winning and the cost of losing escalated hawk-hawk fights. We define evolutionarily stable phenotypes as consisting of an evolutionarily stable strategy and an evolutionarily stable trait, which in turn describes a corresponding evolutionarily stable payoff matrix. CONCLUSIONS: We find that the maximal possible cost of escalating fights remains constant during evolution assuming a separation in the time scales of fast behavioural and slow trait selection, despite the fact that the final evolutionarily stable phenotype maximizes the payoff of hawk-hawk fights. Our results mirror the dual nature of Darwinian evolution whereby the criteria of evolutionary success, as well as the successful phenotypes themselves, are a product of natural selection.

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.

Pervasive relaxed selection in termite genomes.

Genetic changes that enabled the evolution of eusociality have long captivated biologists. More recently, attention has focussed on the consequences of eusociality on genome evolution. Studies have reported higher molecular evolutionary rates in eusocial hymenopteran insects compared with their solitary relatives. To investigate the genomic consequences of eusociality in termites, we analysed nine genomes, including newly sequenced genomes from three non-eusocial cockroaches. Using a phylogenomic approach, we found that termite genomes have experienced lower rates of synonymous substitutions than those of cockroaches, possibly as a result of longer generation times. We identified higher rates of non-synonymous substitutions in termite genomes than in cockroach genomes, and identified pervasive relaxed selection in the former (24-31% of the genes analysed) compared with the latter (2-4%). We infer that this is due to reductions in effective population size, rather than gene-specific effects (e.g. indirect selection of caste-biased genes). We found no obvious signature of increased genetic load in termites, and postulate efficient purging of deleterious alleles at the colony level. Additionally, we identified genomic adaptations that may underpin caste differentiation, such as genes involved in post-translational modifications. Our results provide insights into the evolution of termites and the genomic consequences of eusociality more broadly.

Intraspecific and interspecific variations in the synonymous codon usage in mitochondrial genomes of 8 pleurotus strains.

In this study, we investigated the codon bias of twelve mitochondrial core protein coding genes (PCGs) in eight Pleurotus strains, two of which are from the same species. The results revealed that the codons of all Pleurotus strains had a preference for ending in A/T. Furthermore, the correlation between codon base compositions and codon adaptation index (CAI), codon bias index (CBI) and frequency of optimal codons (FOP) indices was also detected, implying the influence of base composition on codon bias. The two P. ostreatus species were found to have differences in various base bias indicators. The average effective number of codons (ENC) of mitochondrial core PCGs of Pleurotus was found to be less than 35, indicating strong codon preference of mitochondrial core PCGs of Pleurotus. The neutrality plot analysis and PR2-Bias plot analysis further suggested that natural selection plays an important role in Pleurotus codon bias. Additionally, six to ten optimal codons (ΔRSCU > 0.08 and RSCU > 1) were identified in eight Pleurotus strains, with UGU and ACU being the most widely used optimal codons in Pleurotus. Finally, based on the combined mitochondrial sequence and RSCU value, the genetic relationship between different Pleurotus strains was deduced, showing large variations between them. This research has improved our understanding of synonymous codon usage characteristics and evolution of this important fungal group.

The molecular evolution of cancer associated genes in mammals.

Cancer is a disease that many multicellular organisms have faced for millions of years, and species have evolved various tumour suppression mechanisms to control oncogenesis. Although cancer occurs across the tree of life, cancer related mortality risks vary across mammalian orders, with Carnivorans particularly affected. Evolutionary theory predicts different selection pressures on genes associated with cancer progression and suppression, including oncogenes, tumour suppressor genes and immune genes. Therefore, we investigated the evolutionary history of cancer associated gene sequences across 384 mammalian taxa, to detect signatures of selection across categories of oncogenes (GRB2, FGL2 and CDC42), tumour suppressors (LITAF, Casp8 and BRCA2) and immune genes (IL2, CD274 and B2M). This approach allowed us to conduct a fine scale analysis of gene wide and site-specific signatures of selection across mammalian lineages under the lens of cancer susceptibility. Phylogenetic analyses revealed that for most species the evolution of cancer associated genes follows the species' evolution. The gene wide selection analyses revealed oncogenes being the most conserved, tumour suppressor and immune genes having similar amounts of episodic diversifying selection. Despite BRCA2's status as a key caretaker gene, episodic diversifying selection was detected across mammals. The site-specific selection analyses revealed that the two apoptosis associated domains of the Casp8 gene of bats (Chiroptera) are under opposing forces of selection (positive and negative respectively), highlighting the importance of site-specific selection analyses to understand the evolution of highly complex gene families. Our results highlighted the need to critically assess different types of selection pressure on cancer associated genes when investigating evolutionary adaptations to cancer across the tree of life. This study provides an extensive assessment of cancer associated genes in mammals with highly representative, and substantially large sample size for a comparative genomic analysis in the field and identifies various avenues for future research into the mechanisms of cancer resistance and susceptibility in mammals.

Improving selection decisions with mating information by accounting for Mendelian sampling variances looking two generations ahead.

BACKGROUND: Breeding programs are judged by the genetic level of animals that are used to disseminate genetic progress. These animals are typically the best ones of the population. To maximise the genetic level of very good animals in the next generation, parents that are more likely to produce top performing offspring need to be selected. The ability of individuals to produce high-performing progeny differs because of differences in their breeding values and gametic variances. Differences in gametic variances among individuals are caused by differences in heterozygosity and linkage. The use of the gametic Mendelian sampling variance has been proposed before, for use in the usefulness criterion or Index5, and in this work, we extend existing approaches by not only considering the gametic Mendelian sampling variance of individuals, but also of their potential offspring. Thus, the criteria developed in this study plan one additional generation ahead. For simplicity, we assumed that the true quantitative trait loci (QTL) effects, genetic map and the haplotypes of all animals are known. RESULTS: In this study, we propose a new selection criterion, ExpBVSelGrOff, which describes the genetic level of selected grand-offspring that are produced by selected offspring of a particular mating. We compare our criterion with other published criteria in a stochastic simulation of an ongoing breeding program for 21 generations for proof of concept. ExpBVSelGrOff performed better than all other tested criteria, like the usefulness criterion or Index5 which have been proposed in the literature, without compromising short-term gains. After only five generations, when selection is strong (1%), selection based on ExpBVSelGrOff achieved 5.8% more commercial genetic gain and retained 25% more genetic variance without compromising inbreeding rate compared to selection based only on breeding values. CONCLUSIONS: Our proposed selection criterion offers a new tool to accelerate genetic progress for contemporary genomic breeding programs. It retains more genetic variance than previously published criteria that plan less far ahead. Considering future gametic Mendelian sampling variances in the selection process also seems promising for maintaining more genetic variance.

Integration of selective sweeps across the sheep genome: understanding the relationship between production and adaptation traits.

BACKGROUND: Livestock populations are under constant selective pressure for higher productivity levels for different selective purposes. This pressure results in the selection of animals with unique adaptive and production traits. The study of genomic regions associated with these unique characteristics has the potential to improve biological knowledge regarding the adaptive process and how it is connected to production levels and resilience, which is the ability of an animal to adapt to stress or an imbalance in homeostasis. Sheep is a species that has been subjected to several natural and artificial selective pressures during its history, resulting in a highly specialized species for production and adaptation to challenging environments. Here, the data from multiple studies that aim at mapping selective sweeps across the sheep genome associated with production and adaptation traits were integrated to identify confirmed selective sweeps (CSS). RESULTS: In total, 37 studies were used to identify 518 CSS across the sheep genome, which were classified as production (147 prodCSS) and adaptation (219 adapCSS) CSS based on the frequency of each type of associated study. The genes within the CSS were associated with relevant biological processes for adaptation and production. For example, for adapCSS, the associated genes were related to the control of seasonality, circadian rhythm, and thermoregulation. On the other hand, genes associated with prodCSS were related to the control of feeding behaviour, reproduction, and cellular differentiation. In addition, genes harbouring both prodCSS and adapCSS showed an interesting association with lipid metabolism, suggesting a potential role of this process in the regulation of pleiotropic effects between these classes of traits. CONCLUSIONS: The findings of this study contribute to a deeper understanding of the genetic link between productivity and adaptability in sheep breeds. This information may provide insights into the genetic mechanisms that underlie undesirable genetic correlations between these two groups of traits and pave the way for a better understanding of resilience as a positive ability to respond to environmental stressors, where the negative effects on production level are minimized.

The Unification of Evolutionary Dynamics through the Bayesian Decay Factor in a Game on a Graph.

We unify evolutionary dynamics on graphs in strategic uncertainty through a decaying Bayesian update. Our analysis focuses on the Price theorem of selection, which governs replicator(-mutator) dynamics, based on a stratified interaction mechanism and a composite strategy update rule. Our findings suggest that the replication of a certain mutation in a strategy, leading to a shift from competition to cooperation in a well-mixed population, is equivalent to the replication of a strategy in a Bayesian-structured population without any mutation. Likewise, the replication of a strategy in a Bayesian-structured population with a certain mutation, resulting in a move from competition to cooperation, is equivalent to the replication of a strategy in a well-mixed population without any mutation. This equivalence holds when the transition rate from competition to cooperation is equal to the relative strength of selection acting on either competition or cooperation in relation to the selection differential between cooperators and competitors. Our research allows us to identify situations where cooperation is more likely, irrespective of the specific payoff levels. This approach provides new perspectives into the intended purpose of Price's equation, which was initially not designed for this type of analysis.

Residual networks without pooling layers improve the accuracy of genomic predictions.

KEY MESSAGE: Residual neural network genomic selection is the first GS algorithm to reach 35 layers, and its prediction accuracy surpasses previous algorithms. With the decrease in DNA sequencing costs and the development of deep learning, phenotype prediction accuracy by genomic selection (GS) continues to improve. Residual networks, a widely validated deep learning technique, are introduced to deep learning for GS. Since each locus has a different weighted impact on the phenotype, strided convolutions are more suitable for GS problems than pooling layers. Through the above technological innovations, we propose a GS deep learning algorithm, residual neural network for genomic selection (ResGS). ResGS is the first neural network to reach 35 layers in GS. In 15 cases from four public data, the prediction accuracy of ResGS is higher than that of ridge-regression best linear unbiased prediction, support vector regression, random forest, gradient boosting regressor, and deep neural network genomic prediction in most cases. ResGS performs well in dealing with gene-environment interaction. Phenotypes from other environments are imported into ResGS along with genetic data. The prediction results are much better than just providing genetic data as input, which demonstrates the effectiveness of GS multi-modal learning. Standard deviation is recommended as an auxiliary GS evaluation metric, which could improve the distribution of predicted results. Deep learning for GS, such as ResGS, is becoming more accurate in phenotype prediction.

Genome-wide scans for selection signatures in indigenous chickens reveal candidate genes associated with local adaptation.

Population growth and climate change pose challenges to the sustainability of poultry farming. The emphasis on high-yield traits in commercialized breeds has led to a decline in their adaptability. Chicken varieties adapted to the local environment, possessing traits that facilitate adaptation to climate change, such as disease resistance and tolerance to extreme weather conditions, can improve hybridization outcomes. In this study, we conducted an analysis of the population structure and genetic diversity of 110 chickens representing indigenous breeds from southern China and two different commercial breeds. Further, we performed comparative population genomics, utilizing nucleotide diversity and fixation statistics, to characterize genomic features of natural selection and to identify unique genetic traits and potential selection markers developed by indigenous breeds after adapting to the local environment. Results based on genetic diversity and population structure analyses showed that indigenous varieties exhibited high levels of genetic diversity. Commercial breeds that have been indigenously bred demonstrated higher levels of genetic diversity than those that have not, and breeds with different selection practices displayed significant differences in genetic structure. Additionally, we further searched for potential genomic regions in native chicken ecotypes, uncovering several candidate genes related to ecological adaptations affecting local breeds, such as IKBKB, S1PR1, TSHR, IL1RAPL1 and AMY2A, which are involved in disease resistance, heat tolerance, immune regulation and behavioral traits. This work provides important insights into the genomic characterization of ecotypes of native chicken in southern China. The identification of candidate genes associated with traits such as disease resistance, heat tolerance, immunomodulation, and behavioral traits is a significant outcome. These candidate genes may contribute to the understanding of the molecular basis of the adaptation of the southern native chicken to the local environment. It is recommended that these genes be integrated into chicken breeding programs to enhance sustainable agriculture and promote effective conservation and utilization strategies.

Unraveling inbreeding patterns and selection signals in Alpine Grey cattle.

Inbreeding plays a crucial role in livestock breeding, influencing genetic diversity and phenotypic traits. Genomic data have helped address limitations posed by incomplete pedigrees, providing deeper insights into breed genetic diversity. This study assesses inbreeding levels via pedigree and genomic approaches and analyzes old and recent inbreeding using runs of homozygosity (ROH), and selection signals in Alpine Grey cattle. Pedigree data from 165 575 individuals, analyzed with INBUPGF90 software, computed inbreeding coefficients. Genomic-based coefficients derived from PLINK v1.9. or DetectRUNS R package analyses of 1 180 individuals' genotypes. Common single nucleotide polymorphisms within ROH pinpointed genomic regions, aggregating into "ROH islands" indicative of selection pressure. Overlaps with USCS Genome Browser unveiled gene presence. Moderate correlations (0.20-0.54) existed between pedigree and genomic coefficients, with most genomic estimators having higher (>0.8) correlation values. Inbreeding averaged 0.04 in < 8 Mb ROH segments, and 0.03 in > 16 Mb segments; > 90% of ROHs were < 8 Mb, indicating ancient inbreeding prevalence. Recent inbreeding proved less detrimental than in cosmopolitan breeds. Two major ROH islands on chromosomes 6 and 7 harbored genes linked to immune response, disease resistance (PYURF, HERC3), and fertility (EIF4EBP3, SRA1). This study underscores the need for detailed inbreeding analyses to understand genetic characteristics and historical changes in local breeds like Alpine Grey cattle. Genomic insights, especially from ROH, facilitated overcoming pedigree limitations, illuminating breed genetic diversity. Our findings reveal ancient inbreeding's enduring genetic impact and ROH islands potential for selective sweeps, elucidating traits in Alpine Grey cattle.

Genomic analysis uncovers novel candidate genes related to adaptation to tropical climates and milk production traits in native goats.

BACKGROUND: Since domestication, both evolutionary forces and human selection have played crucial roles in producing adaptive and economic traits, resulting in animal breeds that have been selected for specific climates and different breeding goals. Pakistani goat breeds have acquired genomic adaptations to their native climate conditions, such as tropical and hot climates. In this study, using next-generation sequencing data, we aimed to assess the signatures of positive selection in three native Pakistani goats, known as milk production breeds, that have been well adapted to their local climate. RESULTS: To explore the genomic relationship between studied goat populations and their population structure, whole genome sequence data from native goat populations in Pakistan (n = 26) was merged with available worldwide goat genomic data (n = 184), resulting in a total dataset of 210 individuals. The results showed a high genetic correlation between Pakistani goats and samples from North-East Asia. Across all populations analyzed, a higher linkage disequilibrium (LD) level (- 0.59) was found in the Pakistani goat group at a genomic distance of 1 Kb. Our findings from admixture analysis (K = 5 and K = 6) showed no evidence of shared genomic ancestry between Pakistani goats and other goat populations from Asia. The results from genomic selection analysis revealed several candidate genes related to adaptation to tropical/hot climates (such as; KITLG, HSPB9, HSP70, HSPA12B, and HSPA12B) and milk production related-traits (such as IGFBP3, LPL, LEPR, TSHR, and ACACA) in Pakistani native goat breeds. CONCLUSIONS: The results from this study shed light on the structural variation in the DNA of the three native Pakistani goat breeds. Several candidate genes were discovered for adaptation to tropical/hot climates, immune responses, and milk production traits. The identified genes could be exploited in goat breeding programs to select efficient breeds for tropical/hot climate regions.

Comparative whole-genome resequencing to uncover selection signatures linked to litter size in Hu Sheep and five other breeds.

Hu sheep (HS), a breed of sheep carrying the FecB mutation gene, is known for its "year-round estrus and multiple births" and is an ideal model for studying the high fecundity mechanisms of livestock. Through analyzing and comparing the genomic selection features of Hu sheep and other sheep breeds, we identified a series of candidate genes that may play a role in Hu sheep's high fecundity mechanisms. In this study, we conducted whole-genome resequencing on six breeds and screened key mutations significantly correlated with high reproductive traits in sheep. Notably, the CC2D1B gene was selected by the fixation index (FST) and the cross-population composite likelihood ratio (XP-CLR) methods in HS and other five breeds. It was worth noting that the CC2D1B gene in HS was different from that in other sheep breeds, and seven missense mutations have been identified. Furthermore, the linkage disequilibrium (LD) analysis revealed a strong linkage disequilibrium in this specific gene region. Subsequently, by performing different grouping based on FecB genotypes in Hu sheep, genome-wide selective signal analysis screened several genes related to reproduction, such as BMPR1B and PPM1K. Besides, FST analysis identified functional genes related to reproductive traits, including RHEB, HSPA2, PPP1CC, HVCN1, and CCDC63. Additionally, a missense mutation was found in the CCDC63 gene and the haplotype was different between the high reproduction (HR) group and low reproduction (LR) group in HS. In summary, we discovered genetic differentiation among six distinct breeding sheep breeds at the whole genome level. Additionally, we identified a set of genes which were associated with reproductive performance in Hu sheep and visualized how these genes differed in different breeds. These findings laid a theoretical foundation for understanding genetic mechanisms behind high prolific traits in sheep.

Genetic polymorphism and evidence of signatures of selection in the Plasmodium falciparum circumsporozoite protein gene in Tanzanian regions with different malaria endemicity.

BACKGROUND: In 2021 and 2023, the World Health Organization approved RTS,S/AS01 and R21/Matrix M malaria vaccines, respectively, for routine immunization of children in African countries with moderate to high transmission. These vaccines are made of Plasmodium falciparum circumsporozoite protein (PfCSP), but polymorphisms in the gene raise concerns regarding strain-specific responses and the long-term efficacy of these vaccines. This study assessed the Pfcsp genetic diversity, population structure and signatures of selection among parasites from areas of different malaria transmission intensities in Mainland Tanzania, to generate baseline data before the introduction of the malaria vaccines in the country. METHODS: The analysis involved 589 whole genome sequences generated by and as part of the MalariaGEN Community Project. The samples were collected between 2013 and January 2015 from five regions of Mainland Tanzania: Morogoro and Tanga (Muheza) (moderate transmission areas), and Kagera (Muleba), Lindi (Nachingwea), and Kigoma (Ujiji) (high transmission areas). Wright's inbreeding coefficient (Fws), Wright's fixation index (FST), principal component analysis, nucleotide diversity, and Tajima's D were used to assess within-host parasite diversity, population structure and natural selection. RESULTS: Based on Fws (< 0.95), there was high polyclonality (ranging from 69.23% in Nachingwea to 56.9% in Muheza). No population structure was detected in the Pfcsp gene in the five regions (mean FST = 0.0068). The average nucleotide diversity (π), nucleotide differentiation (K) and haplotype diversity (Hd) in the five regions were 4.19, 0.973 and 0.0035, respectively. The C-terminal region of Pfcsp showed high nucleotide diversity at Th2R and Th3R regions. Positive values for the Tajima's D were observed in the Th2R and Th3R regions consistent with balancing selection. The Pfcsp C-terminal sequences revealed 50 different haplotypes (H_1 to H_50), with only 2% of sequences matching the 3D7 strain haplotype (H_50). Conversely, with the NF54 strain, the Pfcsp C-terminal sequences revealed 49 different haplotypes (H_1 to H_49), with only 0.4% of the sequences matching the NF54 strain (Hap_49). CONCLUSIONS: The findings demonstrate high diversity of the Pfcsp gene with limited population differentiation. The Pfcsp gene showed positive Tajima's D values, consistent with balancing selection for variants within Th2R and Th3R regions. The study observed differences between the intended haplotypes incorporated into the design of RTS,S and R21 vaccines and those present in natural parasite populations. Therefore, additional research is warranted, incorporating other regions and more recent data to comprehensively assess trends in genetic diversity within this important gene. Such insights will inform the choice of alleles to be included in the future vaccines.

Insertion-Deletion Events Are Depleted in Protein Regions with Predicted Secondary Structure.

A fundamental goal in evolutionary biology and population genetics is to understand how selection shapes the fate of new mutations. Here, we test the null hypothesis that insertion-deletion (indel) events in protein-coding regions occur randomly with respect to secondary structures. We identified indels across 11,444 sequence alignments in mouse, rat, human, chimp, and dog genomes and then quantified their overlap with four different types of secondary structure-alpha helices, beta strands, protein bends, and protein turns-predicted by deep-learning methods of AlphaFold2. Indels overlapped secondary structures 54% as much as expected and were especially underrepresented over beta strands, which tend to form internal, stable regions of proteins. In contrast, indels were enriched by 155% over regions without any predicted secondary structures. These skews were stronger in the rodent lineages compared to the primate lineages, consistent with population genetic theory predicting that natural selection will be more efficient in species with larger effective population sizes. Nonsynonymous substitutions were also less common in regions of protein secondary structure, although not as strongly reduced as in indels. In a complementary analysis of thousands of human genomes, we showed that indels overlapping secondary structure segregated at significantly lower frequency than indels outside of secondary structure. Taken together, our study shows that indels are selected against if they overlap secondary structure, presumably because they disrupt the tertiary structure and function of a protein.