Detailed characterization of the complete mitochondrial genome of the oceanic whitetip shark Carcharhinus longimanus (Poey, 1861).

BACKGROUND: The oceanic whitetip shark Carcharhinus longimanus (family Carcharhinidae) is one of the largest sharks inhabiting all tropical and subtropical oceanic regions. Due to their life history traits and mortality attributed to pelagic longline fishing practices, this species is experiencing substantial population decline. Currently, C. longimanus is considered by the IUCN Red List of Threatened Species as "vulnerable" throughout its range and "critically endangered" in the western north Atlantic. This study sequences and describes the complete mitochondrial genome of C. longimanus in detail. METHODS AND RESULTS: The mitochondrial genome of C. longimanus was assembled through next-generation sequencing and then analyzed using specialized bioinformatics tools. The circular, double-stranded AT-rich mitogenome of C. longimanus is 16,704 bp long and contains 22 tRNA genes, 2 rRNA genes, 13 protein coding genes and a 1,065 bp long control region (CR). Out of the 22 tRNA genes, only one (tRNA-Ser1) lacked a typical 'cloverleaf' secondary structure. The prevalence of TTA (Leu), ATT (Ile) and CTA (Leu) codons in the PCGs likely contributes to the AT-rich nature of this mitogenome. In the CR, ten microsatellites were detected but no tandem repeats were found. Stem-and-loop secondary structures were common along the entire length of the CR. Ka/Ks values estimated for all PCGs were < 1, indicating that all the PCGs experience purifying selection. A phylomitogenomic analysis based on translated PCGs confirms the sister relationship between C. longimanus and C. obscurus. The analysis did not support the monophyly of the genus Carcharhinus. CONCLUSIONS: The assembled mitochondrial genome of this pelagic shark can provide insight into the phylogenetic relationships in the genus Carcharhinus and aid conservation and management efforts in the Central Pacific Ocean.

Measuring the Efficiency of Purging by non-random Mating in Human Populations.

Human populations harbor a high concentration of deleterious genetic variants. Here, we tested the hypothesis that non-random mating practices affect the distribution of these variants, through exposure in the homozygous state, leading to their purging from the population gene pool. To do so, we produced whole-genome sequencing data for two pairs of Asian populations exhibiting different alliance rules and rates of inbreeding, but with similar effective population sizes. The results show that populations with higher rates of inbred matings do not purge deleterious variants more efficiently. Purging therefore has a low efficiency in human populations, and different mating practices lead to a similar mutational load.

Signatures of Adaptation and Purifying Selection in Highland Populations of Dasiphora fruticosa.

High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland populations identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.

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.

Patterns of Change in Nucleotide Diversity Over Gene Length.

Nucleotide diversity at a site is influenced by the relative strengths of neutral and selective population genetic processes. Therefore, attempts to estimate Effective population size based on the diversity of synonymous sites demand a better understanding of their selective constraints. The nucleotide diversity of a gene was previously found to correlate with its length. In this work, I measure nucleotide diversity at synonymous sites and uncover a pattern of low diversity towards the translation initiation site of a gene. The degree of reduction in diversity at the translation initiation site and the length of this region of reduced diversity can be quantified as "Effect Size" and "Effect Length" respectively, using parameters of an asymptotic regression model. Estimates of Effect Length across bacteria covaried with recombination rates as well as with a multitude of translation-associated traits such as the avoidance of mRNA secondary structure around translation initiation site, the number of rRNAs, and relative codon usage of ribosomal genes. Evolutionary simulations under purifying selection reproduce the observed patterns and diversity-length correlation and highlight that selective constraints on the 5'-region of a gene may be more extensive than previously believed. These results have implications for the estimation of effective population size, and relative mutation rates, and for genome scans of genes under positive selection based on "silent-site" diversity.

A positive selection at binding site 501 in the B.1 lineage might have triggered the highly infectious sub-lineages of SARS-CoV-2.

The descendants of the B lineage are the most predominant variants among the SARS-CoV-2 virus due to the incorporation of new mutations augmenting the infectivity of the virus. There is a substantial increase in the transition transversion bias, nucleotide diversity and purifying selection on the spike protein in the descendants of the B lineage of the SARS-CoV-2 virus on a temporal scale. A strong bias for C-to-U substitutions is found in the genes encoding spike protein in this lineage. The positive selection has operated on the spike gene of B lineages and its sub-lineages. The B.1 lineage has undergone positive selection on site 501 of the receptor binding domain ultimately reflected in a key substitution N501Y in its three descendant lineages namely B.1.1.7, B.1.351 and P.1. The intensity of purifying selection on the multiple sites of the spike gene has increased substantially in the sub-lineages of B.1 in a timescale. The binding site 501 on the spike protein in B lineage is found to coevolve with other amino acid sites. This study sheds light on the evolutionary trajectory of the B lineage into highly infectious descendants in the recent past under the influence of positive and purifying selection exerted by natural immunity and vaccination of the host.

Cloning, characterization, and evolutionary patterns of KCNQ4 genes in anurans.

Acoustic communication plays important roles in the survival and reproduction of anurans. The perception and discrimination of conspecific sound signals of anurans were always affected by masking background noise. Previous studies suggested that some frogs evolved the high-frequency hearing to minimize the low-frequency noise. However, the molecular mechanisms underlying the high-frequency hearing in anurans have not been well explored. Here, we cloned and obtained the coding regions of a high-frequency hearing-related gene (KCNQ4) from 11 representative anuran species and compared them with orthologous sequences from other four anurans. The sequence characteristics and evolutionary analyses suggested the highly conservation of the KCNQ4 gene in anurans, which supported their functional importance. Branch-specific analysis showed that KCNQ4 genes were under different evolutionary forces in anurans and most anuran lineages showed a generally strong purifying selection. Intriguingly, one significantly positively selected site was identified in the anuran KCNQ4 gene based on FEL model. Positive selection was also found along the common ancestor of Ranidae and Rhacophoridae as well as the ancestral O. tianmuii based on the branch-site analysis, and the positively selected sites identified were involved in or near the N-terminal ion transport and the potassium ion channel functional domain of the KCNQ4 genes. The present study revealed valuable information regarding the KCNQ4 genes in anurans and provided some new insights for the underpinnings of the high-frequency hearing in frogs.

Pan-genome insights into adaptive evolution of bacterial symbionts in mixed host-microbe symbioses represented by human gut microbiota Bacteroides cellulosilyticus.

Animal hosts harbor diverse assemblages of microbial symbionts that play crucial roles in the host's lifestyle. The link between microbial symbiosis and host development remains poorly understood. In particular, little is known about the adaptive evolution of gut bacteria in host-microbe symbioses. Recently, symbiotic relationships have been categorized as open, closed, or mixed, reflecting their modes of inter-host transmission and resulting in distinct genomic features. Members of the genus Bacteroides are the most abundant human gut microbiota and possess both probiotic and pathogenic potential, providing an excellent model for studying pan-genome evolution in symbiotic systems. Here, we determined the complete genome of an novel clinical strain PL2022, which was isolated from a blood sample and performed pan-genome analyses on a representative set of Bacteroides cellulosilyticus strains to quantify the influence of the symbiotic relationship on the evolutionary dynamics. B. cellulosilyticus exhibited correlated genomic features with both open and closed symbioses, suggesting a mixed symbiosis. An open pan-genome is characterized by abundant accessory gene families, potential horizontal gene transfer (HGT), and diverse mobile genetic elements (MGEs), indicating an innovative gene pool, mainly associated with genomic islands and plasmids. However, massive parallel gene loss, weak purifying selection, and accumulation of positively selected mutations were the main drivers of genome reduction in B. cellulosilyticus. Metagenomic read recruitment analyses showed that B. cellulosilyticus members are globally distributed and active in human gut habitats, in line with predominant vertical transmission in the human gut. However, existence and/or high abundance were also detected in non-intestinal tissues, other animal hosts, and non-host environments, indicating occasional horizontal transmission to new niches, thereby creating arenas for the acquisition of novel genes. This case study of adaptive evolution under a mixed host-microbe symbiosis advances our understanding of symbiotic pan-genome evolution. Our results highlight the complexity of genetic evolution in this unusual intestinal symbiont.

Genomic Profiling of Insecticide Resistance in Malaria Vectors: Insights into Molecular Mechanisms.

Malaria control faces challenges from widespread insecticide resistance in major Anopheles species. This study, employing a cross-species approach, integrates RNA-Sequencing, whole-genome sequencing, and microarray data to elucidate drivers of insecticide resistance in Anopheles gambiae complex and An. funestus. Findings show an inverse relationship between genetic diversity and gene expression, with highly expressed genes experiencing stronger purifying selection. These genes cluster physically in the genome, revealing potential coordinated regulation. We identified known and novel candidate insecticide resistance genes, enriched in metabolic, cuticular, and behavioural functions. We also present AnoExpress, a Python package, and an online interface for user-friendly exploration of resistance candidate expression. Despite millions of years of speciation, convergent gene expression responses to insecticidal selection pressures are observed across Anopheles species, providing crucial insights for malaria vector control. This study culminates in a rich dataset that allows us to understand molecular mechanisms, better enabling us to combat insecticide resistance effectively.

Positive selection and relaxed purifying selection contribute to rapid evolution of male-biased genes in a dioecious flowering plant.

Sex-biased genes offer insights into the evolution of sexual dimorphism. Sex-biased genes, especially those with male bias, show elevated evolutionary rates of protein sequences driven by positive selection and relaxed purifying selection in animals. Although rapid sequence evolution of sex-biased genes and evolutionary forces have been investigated in animals and brown algae, less is known about evolutionary forces in dioecious angiosperms. In this study, we separately compared the expression of sex-biased genes between female and male floral buds and between female and male flowers at anthesis in dioecious Trichosanthes pilosa (Cucurbitaceae). In floral buds, sex-biased gene expression was pervasive, and had significantly different roles in sexual dimorphism such as physiology. We observed higher rates of sequence evolution for male-biased genes in floral buds compared to female-biased and unbiased genes. Male-biased genes under positive selection were mainly associated with functions to abiotic stress and immune responses, suggesting that high evolutionary rates are driven by adaptive evolution. Additionally, relaxed purifying selection may contribute to accelerated evolution in male-biased genes generated by gene duplication. Our findings, for the first time in angiosperms, suggest evident rapid evolution of male-biased genes, advance our understanding of the patterns and forces driving the evolution of sexual dimorphism in dioecious plants.

Research Note: Possible influence of thermal selection on patterns of HSP70 and HSP90 gene polymorphisms in Thai indigenous and local chicken breeds and red junglefowls.

The thermal stress caused by global climate change adversely affects the welfare, productivity, and reproductive performance of farm animals, including chickens, and causes substantial economic losses. However, the understanding of the genetic basis of the indigenous chicken adaptation to high ambient temperatures is limited. Hence, to reveal the genetic basis of thermal stress adaptation in chickens, this study investigated polymorphisms in the heat shock protein 70 (HSP70) and HSP90 genes, known mechanisms of cellular defense against thermal stress in indigenous and local chicken breeds and red junglefowls in Thailand. The result revealed seven alleles of the HSP70 gene. One allele exhibited a missense mutation, where an amino acid changed from Asn to His in the substrate-binding and peptide-binding domains, which is exclusive to the Lao Pa Koi chicken breed. Twenty new alleles with silent mutations in the HSP90 gene highlighted its greater complexity. Despite this diversity, distinct population structures were not found for either HSP70 or HSP90, which suggests incomplete impact on the domestication process and selection. The low genetic diversity, shown by the sharing of alleles between red junglefowls and Thai indigenous and local chicken breeds, aligns with the hypothesis that these alleles have undergone selection in tropical regions, such as Thailand. Selection signature analysis suggests the purifying selection of HSP70 for thermotolerance. This study provides valuable insights for enhancing the conservation of genetic resources with thermotolerant traits, which are essential for developing breeding programs to increase poultry production in the context of global climate change.

Stochastic processes and changes in evolutionary rate are associated with diversification in a lineage of tropical hard pines (Pinus).

The study of the patterns of polymorphism and molecular evolution among closely related species is key to understanding the evolutionary forces involved in the diversification of lineages. This point is a big challenge in species with slow evolutionary rates, long life cycles, and ancient, shared polymorphisms such as conifers. Under the premise of divergence in a stepwise migration process, we expect clinal geographical patterns of purifying selection efficiency, and genetic structure related to latitude or longitude. If migration is accompanied by changes in the environment, we could further expect a role of positive selection in driving species divergence. Here, we infer patterns of polymorphism, efficiency of purifying selection, and molecular evolution using a dataset of 161 nuclear genes (∼71 Kb) in a lineage of hard pines from North America, the Caribbean, Mexico, and Central America presumed to have migrated from North America toward lower latitudes with tropical conditions. Under the premise of differences in selective pressures, we also look for possible signals of positive selection. To test our hypothesis, first we estimated different indices to infer patterns of polymorphism and efficiency of purifying selection (Ka, Ks, Ka/Ks, dN, dS, dN/dS, and dxy) and compared these metrics across five clades. Also, we investigated possible clinal patterns in these indices and morphological traits (needle length and cone length). Then we inferred genetic structure and environmental differences among species to test for possible signals of positive selection using phylogenetic methods in specific clades. We found differences among clades using Ka, Ks, and Ka/Ks with a relaxation of purifying selection, especially in the Elliotti and Patula clades. We also found environmental differences related to geographic distance, and among clades suggesting differences in selective pressures. The indices Ks, dxy, and needle length had relationships with geography but not ovulate cone length. Finally, we found that most analyzed genes are under purifying selection, but there was an exception of faster evolutionary rate in some pine species, suggesting the possible action of positive selection in divergence. Our study indicated that stochastic processes have played a key role in the diversification of the group, with a possible input of positive selection in pines from Mexico and Central America.

Structural genomic variation and migratory behavior in a wild songbird.

Structural variants (SVs) are a major source of genetic variation; and descriptions in natural populations and connections with phenotypic traits are beginning to accumulate in the literature. We integrated advances in genomic sequencing and animal tracking to begin filling this knowledge gap in the Eurasian blackcap. Specifically, we (a) characterized the genome-wide distribution, frequency, and overall fitness effects of SVs using haplotype-resolved assemblies for 79 birds, and (b) used these SVs to study the genetics of seasonal migration. We detected >15 K SVs. Many SVs overlapped repetitive regions and exhibited evidence of purifying selection suggesting they have overall deleterious effects on fitness. We used estimates of genomic differentiation to identify SVs exhibiting evidence of selection in blackcaps with different migratory strategies. Insertions and deletions dominated the SVs we identified and were associated with genes that are either directly (e.g., regulatory motifs that maintain circadian rhythms) or indirectly (e.g., through immune response) related to migration. We also broke migration down into individual traits (direction, distance, and timing) using existing tracking data and tested if genetic variation at the SVs we identified could account for phenotypic variation at these traits. This was only the case for 1 trait-direction-and 1 specific SV (a deletion on chromosome 27) accounted for much of this variation. Our results highlight the evolutionary importance of SVs in natural populations and provide insight into the genetic basis of seasonal migration.

Assessing the phylogenetic relationship among varieties of Toona ciliata (Meliaceae) in sympatry with chloroplast genomes.

Toona ciliata is an endangered species due to over-cutting and low natural regeneration in China. Its genetic conservation is of an increasing concern. However, several varieties are recognized according to the leaf and flower traits, which complicates genetic conservation of T. ciliata. Here, we sequenced the whole chloroplast genome sequences of three samples for each of four varieties (T. ciliata var. ciliata, T. ciliata var. yunnanensis, T. ciliata var. pubescens, and T. ciliata var. henryi) in sympatry and assessed their phylogenetic relationship at a fine spatial scale. The four varieties had genome sizes ranged from 159,546 to 159,617 bp and had small variations in genome structure. Phylogenomic analysis indicated that the four varieties were genetically well-mixed in branch groups. Genetic diversity from the whole chloroplast genome sequences of 12 samples was low among varieties (average π = 0.0003). Besides, we investigated genetic variation of 58 samples of the four varieties in sympatry using two markers (psaA and trnL-trnF) and showed that genetic differentiation was generally insignificant among varieties (Ф st = 0%-5%). Purifying selection occurred in all protein-coding genes except for the ycf2 gene that was under weak positive selection. Most amino acid sites in all protein-coding genes were under purifying selection except for a few sites that were under positive selection. The chloroplast genome-based phylogeny did not support the morphology-based classification. The overall results implicated that a conservation strategy based on the T. ciliata complex rather than on intraspecific taxon was more appropriate.

Genome-wide characterization of regulator of chromosome condensation 1 (RCC1) gene family in Artemisia annua L. revealed a conservation evolutionary pattern.

BACKGROUND: Artemisia annua is the major source for artemisinin production. The artemisinin content in A. annua is affected by different types of light especially the UV light. UVR8, a member of RCC1 gene family was found to be the UV-B receptor in plants. The gene structures, evolutionary history and expression profile of UVR8 or RCC1 genes remain undiscovered in A. annua. RESULTS: Twenty-two RCC1 genes (AaRCC1) were identified in each haplotype genome of two diploid strains of A. annua, LQ-9 and HAN1. Varied gene structures and sequences among paralogs were observed. The divergence of most RCC1 genes occurred at 46.7 - 51 MYA which overlapped with species divergence of core Asteraceae during the Eocene, while no recent novel RCC1 members were found in A. annua genome. The number of RCC1 genes remained stable among eudicots and RCC1 genes underwent purifying selection. The expression profile of AaRCC1 is analogous to that of Arabidopsis thaliana (AtRCC1) when responding to environmental stress. CONCLUSIONS: This study provided a comprehensive characterization of the AaRCC1 gene family and suggested that RCC1 genes were conserved in gene number, structures, constitution of amino acids and expression profiles among eudicots.

Odorant receptor orthologues from moths display conserved responses to cis-jasmone.

In insects, the odorant receptor (OR) multigene family evolves by the birth-and-death evolutionary model, according to which the OR repertoire of each species has undergone specific gene gains and losses depending on their chemical environment, resulting in taxon-specific OR lineage radiations with different sizes in the phylogenetic trees. Despite the general divergence in the gene family across different insect orders, the ORs in moths seem to be genetically conserved across species, clustered into 23 major clades containing multiple orthologous groups with single-copy gene from each species. We hypothesized that ORs in these orthologous groups are tuned to ecologically important compounds and functionally conserved. cis-Jasmone is one of the compounds that not only primes the plant defense of neighboring receiver plants, but also functions as a behavior regulator to various insects. To test our hypothesis, using Xenopus oocyte recordings, we functionally assayed the orthologues of BmorOR56, which has been characterized as a specific receptor for cis-jasmone. Our results showed highly conserved response specificity of the BmorOR56 orthologues, with all receptors within this group exclusively responding to cis-jasmone. This is supported by the dN/dS analysis, showing that strong purifying selection is acting on this group. Moreover, molecular docking showed that the ligand binding pockets of BmorOR56 orthologues to cis-jasmone are similar. Taken together, our results suggest the high conservation of OR for ecologically important compounds across Heterocera.

The paradoxes of Mycobacterium tuberculosis molecular evolution and consequences for the inference of tuberculosis emergence date.

The date of Mycobacterium tuberculosis complex emergence has been the subject of long debates. New studies joining archaeological efforts with sequencing methods raise high hopes for solving whether this emergence is closer to 70,000 or to 6000 years before present. Inferring the date of emergence of this pathogen based on sequence data requires a molecular clock. Several clocks inferred from different types of loci and/or different samples, using both sound reasoning and reliable data, are actually very different, which we refer to as the paradoxes of M. tuberculosis molecular evolution. After having presented these paradoxes, we will remind the limits of the molecular clocks used in the different studies such as the assumption of homogeneous substitution rate. We will then review recent results that shed new light on the characteristics of M. tuberculosis molecular evolution: traces of diverse selection pressures, the impact of host dynamics, etc. We provide some ideas on what to do next to get nearer to a reliable dating of Mycobacterium tuberculosis complex emergence. Among them, the collection of additional remains from ancient tuberculosis seems still essential.

Sign of APOBEC editing, purifying selection, frameshift, and in-frame nonsense mutations in the microevolution of lumpy skin disease virus.

The lumpy skin disease virus (LSDV), which mostly affects ruminants and causes huge-economic loss, was endemic in Africa, caused outbreaks in the Middle East, and was recently detected in Russia, Serbia, Greece, Bulgaria, Kazakhstan, China, Taiwan, Vietnam, Thailand, and India. However, the role of evolutionary drivers such as codon selection, negative/purifying selection, APOBEC editing, and genetic variations such as frameshift and in-frame nonsense mutations in the LSDVs, which cause outbreaks in cattle in various countries, are still largely unknown. In the present study, a frameshift mutation in LSDV035, LSDV019, LSDV134, and LSDV144 genes and in-frame non-sense mutations in LSDV026, LSDV086, LSDV087, LSDV114, LSDV130, LSDV131, LSDV145, LSDV154, LSDV155, LSDV057, and LSDV081 genes were revealed among different clusters. Based on the available complete genome sequences, the prototype wild-type cluster-1.2.1 virus has been found in other than Africa only in India, the wild-type cluster-1.2.2 virus found in Africa were spread outside Africa, and the recombinant viruses spreading only in Asia and Russia. Although LSD viruses circulating in different countries form a specific cluster, the viruses detected in each specific country are distinguished by frameshift and in-frame nonsense mutations. Furthermore, the present study has brought to light that the selection pressure for codons usage bias is mostly exerted by purifying selection, and this process is possibly caused by APOBEC editing. Overall, the present study sheds light on microevolutions in LSDV, expected to help in future studies towards disturbed ORFs, epidemiological diagnostics, attenuation/vaccine reverts, and predicting the evolutionary direction of LSDVs.

Regulation of defective mitochondrial DNA accumulation and transmission in C. elegans by the programmed cell death and aging pathways.

The heteroplasmic state of eukaryotic cells allows for cryptic accumulation of defective mitochondrial genomes (mtDNA). 'Purifying selection' mechanisms operate to remove such dysfunctional mtDNAs. We found that activators of programmed cell death (PCD), including the CED-3 and CSP-1 caspases, the BH3-only protein CED-13, and PCD corpse engulfment factors, are required in C. elegans to attenuate germline abundance of a 3.1-kb mtDNA deletion mutation, uaDf5, which is normally stably maintained in heteroplasmy with wildtype mtDNA. In contrast, removal of CED-4/Apaf1 or a mutation in the CED-4-interacting prodomain of CED-3, do not increase accumulation of the defective mtDNA, suggesting induction of a non-canonical germline PCD mechanism or non-apoptotic action of the CED-13/caspase axis. We also found that the abundance of germline mtDNAuaDf5 reproducibly increases with age of the mothers. This effect is transmitted to the offspring of mothers, with only partial intergenerational removal of the defective mtDNA. In mutants with elevated mtDNAuaDf5 levels, this removal is enhanced in older mothers, suggesting an age-dependent mechanism of mtDNA quality control. Indeed, we found that both steady-state and age-dependent accumulation rates of uaDf5 are markedly decreased in long-lived, and increased in short-lived, mutants. These findings reveal that regulators of both PCD and the aging program are required for germline mtDNA quality control and its intergenerational transmission.

Genetic diversity and molecular evolution of Seoul virus in Hebei province, China.

Seoul virus (SEOV) is a major pathogen which causes hemorrhagic fever with renal syndrome (HFRS), and is present all over the world. However, there are currently few long-term systematic studies of SEOV's phylogenetic and evolutionary mechanisms in epidemic areas. Thus, in this study, we used RT-PCR combined with NGS to obtain the genomes of six SEOV viruses from 1993, as well as 56 Hebei province-specific tissue samples from 1999 to 2022. Phylogenetic analysis showed that the SEOV samples could be divided into seven groups and showed geographic clustering. The geographic region may be the main factor affecting the genetic diversity of SEOV. We also found that SEOV was subject to strong overall purifying selection and positive selection at certain sites during evolution. Recombination events and high nucleotide substitution rates were also shown to accelerate SEOV's evolution. Evolutionary feature of the L segment is more representative of complete genome. Our detailed analysis provides a deeper understanding of the genetic diversity and evolutionary drivers of SEOV within its primary epidemic areas. It will be important to further monitor epidemiological trends and drivers of variation to help increase our understanding of the pathogenicity of SEOV infections.