Evidence Of Positive Selection Research Articles

Evolutionary and functional analyses of LRP5 in archaic and extant modern humans

BackgroundThe human lineage has undergone a postcranial skeleton gracilization (i.e. lower bone mass and strength relative to body size) compared to other primates and archaic populations such as the Neanderthals. This gracilization has been traditionally explained by differences in the mechanical load that our ancestors exercised. However, there is growing evidence that gracilization could also be genetically influenced.ResultsWe have analyzed the LRP5 gene, which is known to be associated with high bone mineral density conditions, from an evolutionary and functional point of view. Taking advantage of the published genomes of archaic Homo populations, our results suggest that this gene has a complex evolutionary history both between archaic and living humans and within living human populations. In particular, we identified the presence of different selective pressures in archaics and extant modern humans, as well as evidence of positive selection in the African and South East Asian populations from the 1000 Genomes Project. Furthermore, we observed a very limited evidence of archaic introgression in this gene (only at three haplotypes of East Asian ancestry out of the 1000 Genomes), compatible with a general erasing of the fingerprint of archaic introgression due to functional differences in archaics compared to extant modern humans. In agreement with this hypothesis, we observed private mutations in the archaic genomes that we experimentally validated as putatively increasing bone mineral density. In particular, four of five archaic missense mutations affecting the first β-propeller of LRP5 displayed enhanced Wnt pathway activation, of which two also displayed reduced negative regulation.ConclusionsIn summary, these data suggest a genetic component contributing to the understanding of skeletal differences between extant modern humans and archaic Homo populations.

Gene expression, evolution, and the genetics of electrosensing in the smalltooth sawfish, Pristis pectinata.

Sawfishes (Pristidae) are large, highly threatened rays named for their tooth-studded rostrum, which is used for prey sensing and capture. Of all five species, the smalltooth sawfish, Pristis pectinata, has experienced the greatest decline in range, currently found in only ~20% of its historic range. To better understand the genetic underpinnings of these taxonomically and morphologically unique animals, we collected transcriptomic data from several tissue types, mapped them to the recently completed reference genome, and contrasted the patterns observed with comparable data from other elasmobranchs. Evidence of positive selection was detected in 79 genes in P. pectinata, several of which are involved in growth factor/receptor tyrosine kinase signaling and body symmetry and may be related to the unique morphology of sawfishes. Changes in these genes may impact cellular responses to environmental conditions such as temperature, dissolved oxygen, and salinity. Data acquired also allow for examination of the molecular components of P. pectinata electrosensory systems, which are highly developed in sawfishes and have likely been influential in their evolutionary success.

The Klebsiella pneumoniae carbapenemase (KPC) β-Lactamase Has Evolved in Response to Ceftazidime Avibactam.

Klebsiella pneumoniae carbapenemase KPC is an important resistance gene that has disseminated globally in response to carbapenem use. It is now being implicated as a resistance determinant in Ceftazidime Avibactam (CAZ-AVI) resistance. Given that CAZ-AVI is a last-resort antibiotic, it is critical to understand how resistance to this drug is evolving. In particular, we were interested in determining the evolutionary response of KPC to CAZ-AVI consumption. Through phylogenetic reconstruction, we identified the variable sites under positive selection in the KPC gene that are correlated with Ceftazidime Avibactam (CAZ-AVI) resistance. Our approach was to use a phylogeny to identify multiple independent occurrences of mutations at variable sites and a literature review to correlate CAZ-AVI resistance with the mutations we identified. We found the following sites that are under positive selection: P104, W105, A120, R164, L169, A172, D179, V240, Y241, T243, Y264, and H274. The sites that correlate with CAZ-AVI resistance are R164, L169, A172, D179, V240, Y241, T243, and H274. Overall, we found that there is evidence of positive selection in KPC and that CAZ-AVI is the major selective pressure.

Identification of the NOD-like receptor family of golden pompano and expression in response to bacterial and parasitic exposure reveal its key role in innate immunity

This study presents a genome-wide identification of NOD-like receptors (NLRs) in the golden pompano, key to its innate immunity. We identified 30 ToNLRs, analyzing their chromosomal positions, characteristics, evolutionary relationships, evidence of positive selection, and synteny with the yellowtail kingfish. Our findings categorize these NLRs into three main subgroups: NLRA, NLRC, and the distinct ToNLRX1. Post-exposure to Streptococcus agalactiae, most ToNLRs increased expression in the spleen, whereas NLRC3like13, NLRC3like16, and NLRC3like19 so in the kidneys. Upon Cryptocaryon irritans exposure, we categorized our groups based on the site of infection into the control group (BFS), the trophont-attached skin (TAS), and the nearby region skin (NRS). ToAPAF1 and ToNOD1 expressions rose in the NRS, in contrast to decreased expressions of ToNLRC5, ToNWD1 and ToCIITA. Other ToNLRs showed variable expressions in the TAS. Overall, this research lays the groundwork for further exploration of innate immunity in the golden pompano.

Venomous Noodles: The Evolution of Toxins in Nemertea through Positive Selection and Gene Duplication.

Some, probably most and perhaps all, members of the phylum Nemertea are poisonous, documented so far from marine and benthic specimens. Although the toxicity of these animals has been long known, systematic studies on the characterization of toxins, mechanisms of toxicity, and toxin evolution for this group are scarce. Here, we present the first investigation of the molecular evolution of toxins in Nemertea. Using a proteo-transcriptomic approach, we described toxins in the body and poisonous mucus of the pilidiophoran Lineus sanguineus and the hoplonemertean Nemertopsis pamelaroeae. Using these new and publicly available transcriptomes, we investigated the molecular evolution of six selected toxin gene families. In addition, we also characterized in silico the toxin genes found in the interstitial hoplonemertean, Ototyphlonemertes erneba, a meiofaunal taxa. We successfully identified over 200 toxin transcripts in each of these species. Evidence of positive selection and gene duplication was observed in all investigated toxin genes. We hypothesized that the increased rates of gene duplications observed for Pilidiophora could be involved with the expansion of toxin genes. Studies concerning the natural history of Nemertea are still needed to understand the evolution of their toxins. Nevertheless, our results show evolutionary mechanisms similar to other venomous groups.

Phylomitogenomics elucidates the evolution of symbiosis in Thoracotremata (Decapoda: Cryptochiridae, Pinnotheridae, Varunidae).

Thoracotremata belong to the large group of "true" crabs (infraorder Brachyura), and they exhibit a wide range of physiological and morphological adaptations to living in terrestrial, freshwater and marine habitats. Moreover, the clade comprises various symbiotic taxa (Aphanodactylidae, Cryptochiridae, Pinnotheridae, some Varunidae) that are specialised in living with invertebrate hosts, but the evolutionary history of these symbiotic crabs is still partially unresolved. Here we assembled and characterised the complete mitochondrial genomes (hereafter mitogenomes) of three gall crab species (Cryptochiridae): Kroppcarcinus siderastreicola, Opecarcinus hypostegus and Troglocarcinus corallicola. A phylogenetic tree of the Thoracotremata was reconstructed using 13 protein-coding genes and two ribosomal RNA genes retrieved from three new gall crab mitogenomes and a further 72 available thoracotreme mitogenomes. Furthermore, we applied a comparative analysis to characterise mitochondrial gene order arrangement, and performed a selection analysis to test for selective pressure of the protein-coding genes in symbiotic Cryptochiridae, Pinnotheridae, and Varunidae (Asthenognathus inaequipes and Tritodynamia horvathi). The results of the phylogenetic reconstruction confirm the monophyly of Cryptochiridae, which clustered separately from the Pinnotheridae. The latter clustered at the base of the tree with robust branch values. The symbiotic varunids A. inaequipes and T. horvathi clustered together in a clade with free-living Varunidae species, highlighting that symbiosis in the Thoracotremata evolved independently on multiple occasions. Different gene orders were detected in symbionts and free-living species when compared with the ancestral brachyuran gene order. Lastly, the selective pressure analysis detected two positively selected sites in the nad6 gene of Cryptochiridae, but the evidence for positive selection in Pinnotheridae and A. inaequipes and T. horvathi was weak. Adaptive evolution of mitochondrial protein-coding genes is perhaps related to the presumably higher energetic demands of a symbiotic lifestyle.

The biology of hearing and hearing loss: New insights from naked mole-rats into mechanisms and adaptive responses

Understanding the biology of hearing and hearing loss requires not only examination of the existing structure and function of the auditory system but also consideration of its evolutionary legacy. In this context, research in my group, in collaboration with others, utilizes a comparative approach to investigate hearing and hearing loss in various rodent models, including Naked mole-rats—a highly vocal, eusocial, subterranean species exhibiting surprisingly poor hearing for reasons that long remained elusive. Our findings reveal that the comparatively poor hearing in Naked mole-rats results from a combination of factors, including the absence of cochlear amplification, disrupted hair bundles, and hair bundle proteins bearing deafness-associated amino acid substitutions. Intriguingly, evidence of positive selection in some bundle proteins suggests that altered hearing in Naked mole-rats may be an adaptive response to their subterranean and eusocial lifestyles. More recent work investigates the comparative organization of central auditory structures in Naked mole-rats to identify the mechanisms of central compensation that support auditory-vocal communication in this species despite their poor peripheral hearing. Ultimately, the Naked mole-rats serve as a naturally occurring disease model to investigate hearing loss and gain valuable insights into mechanistic approaches to treat hearing loss.

Evolutionary analyses of gene expression divergence in Panicum hallii: exploring constitutive and plastic responses using reciprocal transplants.

The evolution of gene expression is thought to be an important mechanism of local adaptation and ecological speciation. Gene expression divergence occurs through the evolution of cis- polymorphisms and through more widespread effects driven by trans-regulatory factors. Here, we explore expression and sequence divergence in a large sample of Panicum hallii accessions encompassing the species range using a reciprocal transplantation experiment. We observed widespread genotype and transplant site drivers of expression divergence, with a limited number of genes exhibiting genotype-by-site interactions. We used a modified Fst-Qst outlier approach (QPC analysis) to detect local adaptation. We identified 514 genes with constitutive expression divergence above and beyond the levels expected under neutral processes. However, no plastic expression responses met our multiple testing correction as QPC outliers. Constitutive QPC outlier genes were involved in a number of developmental processes and responses to abiotic environments. Leveraging earlier expression quantitative trait loci (eQTL) results (Lovell et al. 2018), we found a strong enrichment of expression divergence, including for QPC outliers, in genes previously identified with cis and cis-environment interactions but found no patterns related to trans-factors. Population genetic analyses detected elevated sequence divergence of promoters and coding sequence of constitutive expression outliers, but little evidence for positive selection on these proteins. Our results are consistent with a hypothesis of cis-regulatory divergence as a primary driver of expression divergence in P. hallii.

Chromosome-level reference genomes of two imperiled desert fishes: spikedace (Meda fulgida) and loach minnow (Tiaroga cobitis).

North American minnows (Cypriniformes: Leuciscidae) comprise a diverse taxonomic group, but many members, particularly those inhabiting deserts, face elevated extinction risks. Despite conservation concerns, leuciscids remain under sampled for reference assemblies relative to other groups of freshwater fishes. Here, we present 2 chromosome-scale reference genome assemblies spikedace (Meda fulgida) and loach minnow (Tiaroga cobitis) using PacBio, Illumina and Omni-C technologies. The complete assembly for spikedace was 882.1 Mb in total length comprised of 83 scaffolds with N50 = 34.8 Mb, L50 = 11, N75 = 32.3 Mb, and L75 = 18. The complete assembly for loach minnow was 1.3 Gb in total length comprised of 550 scaffolds with N50 = 48.6 Mb, L50 = 13, N75 = 42.3 Mb, and L75 = 20. Completeness assessed via Benchmarking Universal Single-Copy Orthologues (BUSCO) metrics using the Actinopterygii BUSCO database showed ∼97% for spikedace and ∼98% for loach minnow of complete BUSCO proportions. Annotation revealed approximately 32.58 and 29.04% of spikedace and loach minnow total genome lengths to be comprised of protein-coding genes, respectively. Comparative genomic analyses of these endangered and co-distributed fishes revealed widespread structural variants, gene family expansions, and evidence of positive selection in both genomes.

Immune gene variation associated with chromosome-scale differences among individual zebrafish genomes

Immune genes have evolved to maintain exceptional diversity, offering robust defense against pathogens. We performed genomic assembly to examine immune gene variation in zebrafish. Gene pathway analysis identified immune genes as significantly enriched among genes with evidence of positive selection. A large subset of genes was absent from analysis of coding sequences due to apparent lack of reads, prompting us to examine genes overlapping zero coverage regions (ZCRs), defined as 2 kb stretches without mapped reads. Immune genes were identified as highly enriched within ZCRs, including over 60% of major histocompatibility complex (MHC) genes and NOD-like receptor (NLR) genes, mediators of direct and indirect pathogen recognition. This variation was most highly concentrated throughout one arm of chromosome 4 carrying a large cluster of NLR genes, associated with large-scale structural variation covering more than half of the chromosome. Our genomic assemblies uncovered alternative haplotypes and distinct complements of immune genes among individual zebrafish, including the MHC Class II locus on chromosome 8 and the NLR gene cluster on chromosome 4. While previous studies have shown marked variation in NLR genes between vertebrate species, our study highlights extensive variation in NLR gene regions between individuals of the same species. Taken together, these findings provide evidence of immune gene variation on a scale previously unknown in other vertebrate species and raise questions about potential impact on immune function.

Conservation and variation in the region of the Theileria parva p104 antigen coding gene used for PCR surveillance of the parasite

The range of the protozoan parasite Theileria parva, which causes East Coast fever in cattle, has been expanding to countries where it has not previously been detected, as a result of cross-border domestic cattle movement. Countries where T. parva has not previously been observed until recently include Cameroon and South Sudan. This raises the issue of the conservation of the p104 antigen gene, on which the nested PCR assay that is widely used for T. parva surveillance in the blood of infected cattle is based. We sampled 40 isolates from six countries widely distributed across the geographical range of the parasite, including eastern, central and southern Africa, for p104 sequence polymorphism. These included parasites from both domestic cattle and the Cape buffalo (Syncerus caffer) wildlife reservoir. The most frequent allelic variants were present in cattle transmissible isolates from multiple widely separated geographical regions in Zambia, Uganda, Kenya, Tanzania, Rwanda and South Africa. These frequent p104 variants were also present in the three component stocks of the Muguga cocktail used for the infection and treatment live immunisation procedure to control T. parva in the field. Other isolates exhibited unique alleles. This includes some of the p104 sequences from Cameroon, which is outside the known range of the Rhipicephalus tick vector and whose origin is therefore unclear. The nested primer oligonucleotides used to generate the amplicons were universally conserved in cattle-derived parasites and a majority of buffalo-derived isolates across the geographical range of the parasite. However, some rare South African buffalo–derived isolates exhibited one or two mismatches with the primer sequences. It therefore remains possible that some p104 alleles may be so divergent that they do not amplify with the current diagnostic primers and are not detectable in surveys, hence the need for increasing knowledge of genetic heterogeneity of diagnostic targets. There was no evidence for positive selection among those p104 mutations that resulted in residue changes. Importantly, the data indicate that the p104-based PCR detection assay should be effective across the majority of the range of T. parva, and if the one or two mismatches are shown in future to result in the primers annealing less efficiently, then the assay can be further improved by introduction of degenerate bases to enable amplification of the less frequent South African buffalo–derived variant p104 genes.

Positive selection in cytochrome P450 genes is associated with gonad phenotype and mating strategy in social bees

The honey bee, Apis mellifera differs from all other social bees in its gonad phenotype and mating strategy. Honey bee queens and drones have tremendously enlarged gonads, and virgin queens mate with several males. In contrast, in all the other bees, the male and female gonads are small, and the females mate with only one or very few males, thus, suggesting an evolutionary and developmental link between gonad phenotype and mating strategy. RNA-seq comparisons of A. mellifera larval gonads revealed 870 genes as differentially expressed in queens versus workers and drones. Based on Gene Ontology enrichment we selected 45 genes for comparing the expression levels of their orthologs in the larval gonads of the bumble bee Bombus terrestris and the stingless bee, Melipona quadrifasciata, which revealed 24 genes as differentially represented. An evolutionary analysis of their orthologs in 13 solitary and social bee genomes revealed four genes with evidence of positive selection. Two of these encode cytochrome P450 proteins, and their gene trees indicated a lineage-specific evolution in the genus Apis, indicating that cytochrome P450 genes may be involved in the evolutionary association of polyandry and the exaggerated gonad phenotype in social bees.

Natural selection and convergent evolution of the HOX gene family in Carnivora

HOX genes play a central role in the development and regulation of limb patterns. For mammals in the order Carnivora, limbs have evolved in different forms, and there are interesting cases of phenotypic convergence, such as the pseudothumb of the giant and red pandas, and the flippers or specialized limbs of the pinnipeds and sea otter. However, the molecular bases of limb development remain largely unclear. Here, we studied the molecular evolution of the HOX9 ~ 13 genes of 14 representative species in Carnivora and explored the molecular evolution of other HOX genes. We found that only one limb development gene, HOXC10, underwent convergent evolution between giant and red pandas and was thus an important candidate gene related to the development of pseudothumbs. No signals of amino acid convergence and natural selection were found in HOX9 ~ 13 genes between pinnipeds and sea otter, but there was evidence of positive selection and rapid evolution in four pinniped species. Overall, few HOX genes evolve via natural selection or convergent evolution, and these could be important candidate genes for further functional validation. Our findings provide insights into potential molecular mechanisms of the development of specialized pseudothumbs and flippers (or specialized limbs).

Extensive MHC class IIβ diversity across multiple loci in the small-spotted catshark (Scyliorhinus canicula)

The major histocompatibility complex (MHC) is a multigene family responsible for pathogen detection, and initiation of adaptive immune responses. Duplication, natural selection, recombination, and their resulting high functional genetic diversity spread across several duplicated loci are the main hallmarks of the MHC. Although these features were described in several jawed vertebrate lineages, a detailed MHC IIβ characterization at the population level is still lacking for chondrichthyans (chimaeras, rays and sharks), i.e. the most basal lineage to possess an MHC-based adaptive immune system. We used the small-spotted catshark (Scyliorhinus canicula, Carcharhiniformes) as a case-study species to characterize MHC IIβ diversity using complementary molecular tools, including publicly available genome and transcriptome datasets, and a newly developed high-throughput Illumina sequencing protocol. We identified three MHC IIβ loci within the same genomic region, all of which are expressed in different tissues. Genetic screening of the exon 2 in 41 individuals of S. canicula from a single population revealed high levels of sequence diversity, evidence for positive selection, and footprints of recombination. Moreover, the results also suggest the presence of copy number variation in MHC IIβ genes. Thus, the small-spotted catshark exhibits characteristics of functional MHC IIβ genes typically observed in other jawed vertebrates.

Investigation of the Molecular Evolution of Treg Suppression Mechanisms Indicates a Convergent Origin.

Regulatory T cell (Treg) suppression of conventional T cells is a central mechanism that ensures immune system homeostasis. The exact time point of Treg emergence is still disputed. Furthermore, the time of Treg-mediated suppression mechanisms’ emergence has not been identified. It is not yet known whether Treg suppression mechanisms diverged from a single pathway or converged from several sources. We investigated the evolutionary history of Treg suppression pathways using various phylogenetic analysis tools. To ensure the conservation of function for investigated proteins, we augmented our study using nonhomology-based methods to predict protein functions among various investigated species and mined the literature for experimental evidence of functional convergence. Our results indicate that a minority of Treg suppressor mechanisms could be homologs of ancient conserved pathways. For example, CD73, an enzymatic pathway known to play an essential role in invertebrates, is highly conserved between invertebrates and vertebrates, with no evidence of positive selection (w = 0.48, p-value < 0.00001). Our findings indicate that Tregs utilize homologs of proteins that diverged in early vertebrates. However, our findings do not exclude the possibility of a more evolutionary pattern following the duplication degeneration−complementation (DDC) model. Ancestral sequence reconstruction showed that Treg suppression mechanism proteins do not belong to one family; rather, their emergence seems to follow a convergent evolutionary pattern.

Morphological Characteristics and Comparative Chloroplast Genome Analyses between Red and White Flower Phenotypes of Pyracantha fortuneana (Maxim.) Li (Rosaceae), with Implications for Taxonomy and Phylogeny.

Pyracantha fortuneana (Maxim.) Li (Rosaceae), commonly known as Chinese firethorn, is an evergreen shrub with high nutritional, medicinal, and horticultural importance. This species typically has white flowers, but a rare red flower phenotype has been found in very few wild populations in western Hubei, China, showing great ornamental potential. In this study, the complete chloroplast genome of the red flower phenotype of P. fortuneana was reported for the first time, using high-throughput sequencing technology. The complete chloroplast genome was 160,361 bp in length and showed a typical quadripartite structure with a pair of inverted repeat (IR) regions (26,350 bp) separated by a large single-copy (LSC) region (88,316 bp) and a small single-copy (SSC) region (19,345 bp). A total of 131 functional genes were annotated in this chloroplast genome, including 86 protein-coding genes (PCGs), eight rRNA genes, and 37 tRNA genes. Comparative chloroplast genome analyses revealed that high genome similarity existed not only between red and white flower phenotypes of P. fortuneana, but also among Pyracantha species. No evidence for positive selection was found in any PCG, suggesting the evolutionary conservation of Pyracantha chloroplast genomes. Furthermore, four mutational hotspots (trnG-trnR-atpA, psbZ-trnG-trnfM-rps14, ycf3-trnS-rps4, and ndhF-rpl32) with π > 0.004 were identified as potential molecular markers for Pyracantha species. Phylogenomic analysis strongly supported that the red flower phenotype of P. fortuneana was nested within the common white flower phenotype. Based on both morphological and molecular evidence, we suggest that the red flower phenotype of P. fortuneana could be considered as a new forma. Overall, the availability of these genetic resources will not only offer valuable information for further studies on molecular taxonomy, phylogeny, and population genetics of Pyracantha species but also could be used as potential genetic resources for Chinese firethorn breeding.

Disparate selection of mutations in the dihydrofolate reductase gene (dhfr) of Plasmodium ovale curtisi and P. o. wallikeri in Africa.

Plasmodium ovale curtisi and P. ovale wallikeri are both endemic in sub-Saharan Africa, the Middle East and Southeast Asia. Molecular surveillance data for drug resistance in P. ovale spp. is limited at present. We analysed polymorphisms in the podhfr, pocrt and pocytb genes of P. ovale spp. in 147 samples collected from travelers returning to China from Africa. Two podhfr mutations, S58R and S113N/T were detected in P. ovale curtisi with high/moderate frequencies of 52.17% and 17.39%, respectively. Evidence of positive selection (dN/dS = 2.41) was found for podhfr in P. ovale curtisi and decreased diversity (He) of microsatellite markers flanking the mutant alleles suggests that selective sweeps have occurred for both. Mutations E34G (1.50%) and L43V (1.50%) in pocrt of P. ovale curtisi, and E34G (3.70%), I102M (1.80%) and V111F (1.80%) of P. ovale wallikeri were found at low frequencies. Mutations R66K (6.20%), R75K (11.63%) and R95K (3.88%) of pocytb were found in both P. ovale curtisi and P. ovale wallikeri. These results suggest that the podhfr gene of P. ovale curtisi may be subject to drug selection in Africa, warranting further attention. We observed significant differences in the prevalence and distribution of podhfr mutations between the two P. ovale species, suggestive of fundamental biological differences between them.

Novel genome sequences and evolutionary dynamics of the North American anopheline species Anopheles freeborni, Anopheles crucians, Anopheles quadrimaculatus, and Anopheles albimanus.

Anopheles mosquitoes are the principal vectors for malaria and lymphatic filariasis, and evidence for arboviral transmission under laboratory and natural contexts has been demonstrated. Vector management approaches require an understanding of the ecological, epidemiological, and biological contexts of the species in question, and increased interest in gene drive systems for vector control applications has resulted in an increased need for genome assemblies from understudied mosquito vector species. In this study, we present novel genome assemblies for Anopheles crucians, Anopheles freeborni, Anopheles albimanus, and Anopheles quadrimaculatus and examine the evolutionary relationship between these species. We identified 790 shared single-copy orthologs between the newly sequenced genomes and created a phylogeny using 673 of the orthologs, identifying 289 orthologs with evidence for positive selection on at least 1 branch of the phylogeny. Gene ontology terms such as calcium ion signaling, histone binding, and protein acetylation identified as being biased in the set of selected genes. These novel genome sequences will be useful in developing our understanding of the diverse biological traits that drive vectorial capacity in anophelines.

Genetic diversity in the transmission-blocking vaccine candidate Plasmodium vivax gametocyte protein Pvs230 from the China–Myanmar border area and central Myanmar

BackgroundSexual stage surface antigens are potential targets of transmission-blocking vaccines (TBVs). The gametocyte and gamete surface antigen P230, a leading TBV candidate, is critical for red blood cell binding during exflagellation and subsequent oocyst development. Here, the genetic diversity of Pvs230 was studied in Plasmodium vivax parasite isolates from the China–Myanmar border (CMB) and central Myanmar.MethodsPlasmodium vivax isolates were collected in clinics from malaria-endemic areas of the CMB (143 samples) and Myanmar (23 samples). The interspecies variable part (IVP, nucleotides 1–807) and interspecies conserved part (ICP, 808–2862) of Pvs230 were amplified by PCR and sequenced. Molecular evolution studies were conducted to evaluate the genetic diversity, signature of selection, population differentiation, haplotype network, and population structure of the study parasite populations and publicly available Pvs230 sequences from six global P. vivax populations.ResultsLimited genetic diversity was observed for the CMB (π = 0.002) and Myanmar (π = 0.001) isolates. Most amino acid substitutions were located in the IVP and cysteine-rich domain of Pvs230. Evidence of positive selection was observed for IVP and purifying selection for ICP. Codon-based tests identified specific codons under natural selection in both IVP and ICP. The fixation index (FST) showed low genetic differentiation between East and Southeast Asian populations, with FST ranging from 0.018 to 0.119. The highest FST value (FST = 0.503) was detected between the Turkey and Papua New Guinea populations. A total of 92 haplotypes were identified in global isolates, with the major haplotypes 2 and 9 being the most abundant and circulating in East and Southeast Asia populations. Several detected non-synonymous substitutions were mapped in the predicted structure and B-cell epitopes of Pvs230.ConclusionsWe detected low levels of genetic diversity of Pvs230 in global P. vivax populations. Geographically specific haplotypes were identified for Pvs230. Some mutations are located within a potential B-cell epitope region and need to be considered in future TBV designs.Graphical

Phylogenomics of trophically diverse cichlids disentangles processes driving adaptive radiation and repeated trophic transitions.

Cichlid fishes of the tribe Tropheini are a striking case of adaptive radiation, exemplifying multiple trophic transitions between herbivory and carnivory occurring in sympatry with other established cichlid lineages. Tropheini evolved highly specialized eco‐morphologies to exploit similar trophic niches in different ways repeatedly and rapidly. To better understand the evolutionary history and trophic adaptations of this lineage, we generated a dataset of 532 targeted loci from 21 out of the 22 described Tropheini species. We resolved the Tropheini into seven monophyletic genera and discovered one to be polyphyletic. The polyphyletic genus, Petrochromis, represents three convergent origins of the algae grazing trophic specialization. This repeated evolution of grazing may have been facilitated by adaptive introgression as we found evidence for gene flow among algae grazing genera. We also found evidence of gene flow among algae browsing genera, but gene flow was restricted between herbivorous and carnivorous genera. Furthermore, we observed no evidence supporting a hybrid origin of this radiation. Our molecular evolutionary analyses suggest that opsin genes likely evolved in response to selection pressures associated with trophic ecology in the Tropheini. We found surprisingly little evidence of positive selection in coding regions of jaw‐shaping genes in this trophically diverse lineage. This suggests low degrees of freedom for further change in these genes, and possibly a larger role for regulatory variation in driving jaw adaptations. Our study emphasizes Tropheini cichlids as an important model for studying the evolution of trophic specialization and its role in speciation.