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PubMed2026

High levels of mitotic gene conversion are needed to effectively purge deleterious mutations in asexual organisms.

Self-fertilisation and asexual reproduction are both hypothesised to cause long-term extinction due to inefficient selection against deleterious mutations. Self-fertilisation can counter these effects through creating homozygous genotypes and purging deleterious mutations. Although complete asexuality lacks meiotic gene exchange, mitotic gene conversion creates homozygous regions that could limit deleterious mutation accumulation in an analogous manner. We compare mutation accumulation in self-fertilising and facultative sexual populations subject to mitotic gene conversion, and quantify the efficacy of purging in the latter. We first show analytically that purging is most effective with high levels of asexuality and gene conversion, and when deleterious mutations are recessive. We further show using simulations that, when mitotic gene conversion becomes sufficiently high in obligate asexuals, there is a reduction in the mutation count and a jump in homozygosity, reflecting purging. However, this mechanism is not necessarily as efficient at purging under high self-fertilisation, and elevated rates of mitotic gene conversion seem to be needed for widespread purging compared to empirical estimates. If gene conversion rates are allowed to evolve, then elevated rates that increase mean fitness can arise, but only if there is sufficient variance in the gene conversion rate. Conversely, if gene conversion rates are already high and rates are not constrained then they will slightly decrease, reducing mean fitness.

Self-fertilisation↗

PubMed2025

Compensatory Evolution Following Deleterious Episodes of GC-biased Gene Conversion in Rodents.

GC-biased gene conversion (gBGC) is a widespread evolutionary force associated with meiotic recombination that favors the accumulation of deleterious AT to GC substitutions in proteins, moving them away from their fitness optimum. In many mammals, recombination hotspots have a rapid turnover, leading to episodic gBGC, with the accumulation of deleterious mutations stopping when the recombination hotspot dies. Selection is therefore expected to act to repair the damage caused by gBGC episodes through compensatory evolution. However, this process has never been studied or quantified so far. Here, we analyzed the nucleotide substitution pattern in coding sequences of a highly diversified group of Murinae rodents. Using phylogenetic analyses of about 70,000 coding exons, we identified numerous exon-specific, lineage-specific gBGC episodes, characterized by a clustering of synonymous AT to GC substitutions and by an increasing rate of nonsynonymous AT to GC substitutions, many of which are potentially deleterious. Analyzing the molecular evolution of the affected exons in downstream lineages, we found evidence for pervasive compensatory evolution after deleterious gBGC episodes. Compensation appears to occur rapidly after the end of the episode and to be driven by the standing genetic variation rather than new mutations. Our results demonstrate the impact of gBGC on the evolution of amino-acid sequences and underline the key role of epistasis in protein adaptation. This study contributes to a growing body of literature emphasizing that adaptive mutations, which arise in response to environmental changes, are just 1 subset of beneficial mutations, alongside mutations resulting from oscillations around the fitness optimum.

Gene Conversion↗

PubMed2025

Ectopic Gene Conversion Causing Quantitative Trait Variation.

Why is there so much non-neutral genetic variation segregating in natural populations? We dissect function and evolution of a near-cryptic quantitative trait locus (QTL) for defense metabolites in Arabidopsis using the CRISPR/Cas9 system and nucleotide polymorphism patterns. The QTL is explained by genetic variation in a family of 4 tightly linked indole-glucosinolate O-methyltransferase genes. Some of this variation appears to be maintained by balancing selection, some appears to be generated by non-reciprocal transfer of sequence, also known as ectopic gene conversion (EGC), between functionally diverged gene copies. Here, we elucidate how EGC, as an inevitable consequence of gene duplication, could be a general mechanism for generating genetic variation for fitness traits.

Quantitative Trait Loci↗

PubMed2026

The SMN locus in the T2T era: Structure, gene conversion, and clinical implications.

Long-read sequencing, paralog-aware variant calling, and telomere-to-telomere (T2T) human genome assemblies now enable the resolution of copy-, haplotype-, and nucleotide-level complexities in segmentally duplicated loci, which were previously inaccessible with short-read sequencing. In this review, we highlight how current technologies and analysis methods reveal extensive diversity in copy number (CN), structure, and gene conversion within the spinal muscular atrophy-associated survival motor neuron (SMN) locus. We summarize how understanding population-level structural variation could be translated into clinical practice, where a nucleotide-level view of the SMN locus may refine prognostic accuracy beyond SMN2 CN and explain variable treatment responses. Finally, we discuss how the approaches and methodologies required to study the SMN locus may be applied elsewhere, providing a scaffold to characterize other complex human genetic regions.

Humans↗

PubMed2025

Characterization of non-crossover recombination spectrum by single-microspore sequencing in maize and rice.

Meiotic DNA double-strand breaks (DSB) are crucial for chromosome recombination. The repair of DSB gives two outcomes: crossover (CO) and non-crossover (NCO). CO involves the bidirectional exchange between homologous chromosomes, whereas NCO refers to the unidirectional transfer of chromosome fragments. NCO can be categorized into NCO with gene conversion and NCO without gene conversion. Due to technological constraints, previous studies have focused more on CO than on NCO. In this study, we isolated single microspores from meiotic tetrads of maize (Zea mays) and rice (Oryza sativa) and conducted deep single-microspore genome sequencing to characterize NCO gene conversion (NCO-GC). Under highly stringent conditions, 101 CO and 902 NCO-GC tracts were identified in four maize tetrads, while 173 CO and 279 NCO-GC tracts were identified in six rice tetrads. In both maize and rice, NCO-GC was more prone to occur in the upstream and downstream of genes, as well as the introns. It also had a significant distribution in transposon regions. A common A-rich motif was enriched in the NCO-GC tracts of maize and rice. GC-biased gene conversion (gBGC) likely contributed to the bimodality of the GC content at the third codon position (GC3), and we discovered a significant proportional relationship between the number of DSBs and the GC content. These findings provide evidence that NCO-GC exhibits a distinct pattern compared with CO and may play an important role in gene and genome evolution.

Oryza↗

PubMed2025

The mutation landscape of Daphnia obtusa reveals evolutionary forces shaping genome stability.

Spontaneous mutations are the primary source of genetic variation and play a central role in shaping evolutionary processes. To investigate mutational dynamics in Daphnia obtusa, we generated a chromosome-level genome assembly spanning 129.4 Mb across 12 chromosomes, encompassing 15,321 predicted protein-coding genes. Leveraging whole-genome sequencing of eight mutation accumulation (MA) lines propagated for an average of 482 generations (spanning over 20 years), we estimated a spontaneous single nucleotide mutation (SNM) rate of 2.23 × 10-9 and an indel mutation rate of 2.75 × 10-10 per site per generation. The SNM spectrum was strongly biased toward C:G > T:A transitions. Comparative analyses with natural population data revealed that exonic mutations observed in the MA lines were significantly less likely to be present in standing variation than intronic or intergenic mutations, suggesting that purifying selection in natural populations acts to remove deleterious alleles. We also identified 48 de novo loss-of-heterozygosity (LOH) events, comprising 8 heterozygous deletions and 40 gene conversion events. The genome-wide gene conversion rate was estimated at 2.62 × 10-5 per heterozygous site per generation. These findings provide a comprehensive view of the mutation spectrum, selective pressures, and mechanisms underlying genome stability in D. obtusa.

Daphnia obtusa↗

PubMed2024

High prevalence of PRDM9-independent recombination hotspots in placental mammals.

In many mammals, recombination events are concentrated in hotspots directed by a sequence-specific DNA-binding protein named PRDM9. Intriguingly, PRDM9 has been lost several times in vertebrates, and notably among mammals, it has been pseudogenized in the ancestor of canids. In the absence of PRDM9, recombination hotspots tend to occur in promoter-like features such as CpG islands. It has thus been proposed that one role of PRDM9 could be to direct recombination away from PRDM9-independent hotspots. However, the ability of PRDM9 to direct recombination hotspots has been assessed in only a handful of species, and a clear picture of how much recombination occurs outside of PRDM9-directed hotspots in mammals is still lacking. In this study, we derived an estimator of past recombination activity based on signatures of GC-biased gene conversion in substitution patterns. We quantified recombination activity in PRDM9-independent hotspots in 52 species of boreoeutherian mammals. We observe a wide range of recombination rates at these loci: several species (such as mice, humans, some felids, or cetaceans) show a deficit of recombination, while a majority of mammals display a clear peak of recombination. Our results demonstrate that PRDM9-directed and PRDM9-independent hotspots can coexist in mammals and that their coexistence appears to be the rule rather than the exception. Additionally, we show that the location of PRDM9-independent hotspots is relatively more stable than that of PRDM9-directed hotspots, but that PRDM9-independent hotspots nevertheless evolve slowly in concert with DNA hypomethylation.

Animals↗

PubMed2026

Circadian reprogramming of inflammation and metabolism in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is driven by inflammation, fibrosis, and metabolic dysfunction. While circadian rhythm dysregulation is well documented in chronic disorders, its specific impact on CKD pathogenesis remains elusive. METHODS: We performed four-hour interval time-series RNA sequencing on renal tissues from control and CKD mice. We used the JTK_CYCLE algorithm to identify rhythmic genes and categorize them as lost, acquired, or sustained in CKD; we subsequently performed focused bioinformatic analyses. RESULTS: The renal circadian profile was substantially altered; acquired rhythmicity emerged as the dominant pattern, and core clock gene expression was disrupted. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that upregulated acquired-rhythmic genes in CKD were enriched in immune-inflammatory pathways; the expression of these genes peaked at Zeitgeber time (ZT) 12-16, consistent with a higher level of renal macrophage infiltration at ZT16 than at ZT0. Conversely, genes associated with nutrient and energy metabolism pathways were downregulated but acquired rhythmicity in CKD. Dapagliflozin improved renal function and restored the circadian expression rhythms of NR1D1 and p-BMAL1. CONCLUSIONS: CKD profoundly remodels the renal circadian transcriptome, driving immune-inflammatory and metabolic pathways into maladaptive rhythmicity. Furthermore, dapagliflozin can partially restore the expression of renal core clock genes.

Animals↗

PubMed2026

Pervasive positive selection on X-linked ampliconic genes in primates.

Mammalian sex chromosomes harbour ampliconic gene families, which are multi-copy genes with ≥97% sequence identity, predominantly expressed in testis tissue and essential for male fertility. The amplification of testis-specific genes is conserved across mammals, yet the specific gene families that expand show striking lineage-specific variation. Previous studies suggest a dynamic turnover with adaptive evolution for several of these families, but their analysis has been limited by the quality of reference genomes of repetitive regions. To characterise the molecular evolutionary processes of ampliconic gene families on both sex chromosomes, we analysed telomere-to-telomere genome assemblies from eight primate species spanning 25 million years of evolution. We identified 53 X-linked and 19 Y-linked ampliconic gene families with dynamic copy number variation. Gene conversion through palindromic pairing and tandem arrays maintained high sequence similarity despite accumulating mutations. X-linked families maintained conserved chromosomal positions despite copy number changes, whereas Y-linked families showed frequent positional turnover. Strikingly, multiple X-linked families (GAGE, SSX, CSAG, and VCX) showed pervasive positive selection across the primate phylogeny and multiple (MAGEB, CT45, HSFX) showed lineage specific positive selection. Y-linked families predominantly evolve under purifying selection. Examining intraspecific copy number variation of the X-linked ampliconic families in chimpanzees, humans, and gorillas, we found variation among individuals but clear differences between species, with the largest families varying the most. These patterns could suggest that sperm competition, meiotic drive, or dosage-dependent selection drive the rapid, lineage-specific evolution of testis-expressed ampliconic genes in primates.

Journal Article↗

PubMed2025

Nationwide carrier screening for congenital adrenal hyperplasia: integrated approach of CYP21A2 pathogenic variant genotyping and comprehensive large gene deletion analysis.

BACKGROUND: Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD CAH) is an autosomal recessive disorder resulting from pathogenic variants in the CYP21A2 gene. The disorder exhibits variable clinical severity, with the classical form manifesting as salt-wasting crisis in neonates, while inducing ambiguous genitalia in females and precocious puberty in males through simple virilization. Identifying at-risk couples during the preconception stage holds significance for optimizing reproductive choices. METHODS: This study included 204 unrelated preconception individuals undergoing carrier screening. A robust molecular approach was devised for rapid detection of nine prevalent CYP21A2 pathogenic variants, utilizing Amplification-Refractory Mutation System (ARMS) PCR and mass spectrometry (MS) genotyping. Complementary quantitative real-time PCR (qPCR) and PCR-based Restriction Fragment Length Polymorphism (PCR-based RFLP) assays were employed for comprehensive gene deletion analysis. The concordance of pathogenic variant detection between ARMS-PCR and MS, as well as the consistency observed in molecular insights from qPCR and PCR-based RFLP, fortified the accuracy of our methodologies. RESULTS: Our combined method could detect common pathogenic variants and large gene deletions with high concordance between ARMS-PCR, MS genotyping, qPCR, and PCR-based RFLP assays. Remarkably, two carriers exhibited significant large-scale deletions, while another manifested a carrier state due to minor-scale gene conversion. The estimated carrier frequency in our cohort using these methods was approximately 1 in 65 individuals. CONCLUSIONS: The methods used for 21-OHD CAH carrier screening offer a reliable, swift, and cost-effective approach for detecting common pathogenic variants and large deletions. Despite some limitations, such as the inability to detect all rare mutations, the techniques provide a practical solution for carrier screening, with an estimated carrier frequency of 1 in 65 in our study population. These findings support the potential adoption of these methods in national carrier screening programs, offering a practical balance between efficiency and affordability.

Humans↗

PubMed2025

The complex evolution and genomic dynamics of mating-type loci in Cryptococcus and Kwoniella.

Sexual reproduction in basidiomycete fungi is governed by MAT loci (P/R and HD), which exhibit remarkable evolutionary plasticity, characterized by expansions, rearrangements, and gene losses often associated with mating system transitions. The sister genera Cryptococcus and Kwoniella provide a powerful framework for studying MAT loci evolution owing to their diverse reproductive strategies and distinct architectures, spanning bipolar and tetrapolar systems with either linked or unlinked MAT loci. Building on recent comparative genomic analyses, we generated additional chromosome-level assemblies, uncovering distinct trajectories shaping MAT loci organization. Contrasting with the small-scale expansions and gene acquisitions observed in Kwoniella, our analyses revealed independent expansions of the P/R locus in tetrapolar Cryptococcus, possibly driven by pheromone gene duplications. Notably, these expansions coincided with a pronounced GC-content reduction best explained by reduced GC-biased gene conversion following recombination suppression, rather than relaxed codon usage selection. Diverse modes of MAT locus linkage were also identified, including three previously unrecognized transitions: one resulting in a pseudobipolar arrangement and two leading to bipolarity. All three transitions involved translocations. In the pseudobipolar configuration, the P/R and HD loci remained on the same chromosome but genetically unlinked, whereas the bipolar transitions additionally featured rearrangements that fused the two loci into a nonrecombining region. Mating assays confirmed a sexual cycle in Cryptococcus decagattii, demonstrating its ability to undergo mating and sporulation. Progeny analysis in Kwoniella mangrovensis revealed substantial ploidy variation and aneuploidy, likely stemming from haploid-diploid mating, yet evidence of recombination and loss of heterozygosity indicates that meiotic exchange occurs despite irregular chromosome segregation. Our findings underscore the importance of continued diversity sampling and provide further evidence for convergent evolution of fused MAT loci in basidiomycetes, offering new insights into the genetic and chromosomal changes driving reproductive transitions.

Genes, Mating Type, Fungal↗

PubMed2025

Tracing the evolution and genomic dynamics of mating-type loci in Cryptococcus pathogens and closely related species.

Sexual reproduction in basidiomycete fungi is governed by MAT loci (P/R and HD), which exhibit remarkable evolutionary plasticity, characterized by expansions, rearrangements, and gene losses often associated with mating system transitions. The sister genera Cryptococcus and Kwoniella provide a powerful framework for studying MAT loci evolution owing to their diverse reproductive strategies and distinct architectures, spanning bipolar and tetrapolar systems with either linked or unlinked MAT loci. Building on recent comparative genomic analyses, we generated additional chromosome-level assemblies, uncovering distinct trajectories shaping MAT loci organization. Contrasting with the small-scale expansions and gene acquisitions observed in Kwoniella, our analyses revealed independent expansions of the P/R locus in tetrapolar Cryptococcus, possibly driven by pheromone gene duplications. Notably, these expansions coincided with a pronounced GC-content reduction best explained by reduced GC-biased gene conversion following recombination suppression, rather than relaxed codon usage selection. Diverse modes of MAT locus linkage were also identified, including three previously unrecognized transitions: one resulting in a pseudobipolar arrangement and two leading to bipolarity. All three transitions involved translocations. In the pseudobipolar configuration, the P/R and HD loci remained on the same chromosome but genetically unlinked, whereas the bipolar transitions additionally featured rearrangements that fused the two loci into a nonrecombining region. Mating assays confirmed a sexual cycle in C. decagattii, demonstrating its ability to undergo mating and sporulation. Progeny analysis in K. mangrovensis revealed substantial ploidy variation and aneuploidy, likely stemming from haploid-diploid mating, yet evidence of recombination and loss of heterozygosity indicates that meiotic exchange occurs despite irregular chromosome segregation. Our findings underscore the importance of continued diversity sampling and provide further evidence for convergent evolution of fused MAT loci in basidiomycetes, offering new insights into the genetic and chromosomal changes driving reproductive transitions.

MAT genes↗

PubMed2026

Decreased expression of Krüppel-like factor 4 is associated with colorectal cancer progression.

Krüppel-like factor 4 (KLF4), a key transcription factor,plays an important role in cell proliferation, differentiation, and apoptosis. Here, we explored the prognostic value of KLF4 and its role in colorectal cancer (CRC) progression. We analyzed transcriptomic data and clinical information related to CRC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. database. Immunohistochemistry was performed to evaluate KLF4 expression in CRC tissue samples. Additionally, we examined the relationship between clinicopathological factors and patient prognosis using Cox proportional hazards model analysis. Lentiviral transfection was used to create KLF4 knockdown HCT-116 cells. Analysis of the TCGA database and two GEO datasets (GSE21510 and GSE117606) revealed that KLF4 was expressed at low levels in CRC. Furthermore, reduced KLF4 levels correlated with lymph node metastasis, distant metastasis, and advanced TNM staging. ROC curve analysis indicated that KLF4 can effectively differentiate cancerous tissue from normal tissue. Functional enrichment analysis identified KLF4 as significantly linked to the glycoprotein metabolic pathway. Our detection of KLF4 expression in CRC tissue samples confirmed its decreased levels and their association with poorer patient survival. However, KLF4 was not identified as an independent prognostic factor. In vitro, KLF4 knockdown promoted HCT-116 cell migration and invasion and downregulated the mRNA expression of glycoprotein synthesis- and glycosylation-related genes. Conversely, KLF4 re-expression markedly reversed these effects. Our findings suggested that low KLF4 expression served as a predictor factor for disease progression in CRC patients. Furthermore, reduced KLF4 levels enhance the migration and invasion of CRC cells, which may be related to impaired glycoprotein metabolism.

Colorectal cancer↗

PubMed2025

Global Environmental Factors Impact the Evolution of Adult Hemoglobins in Squamata Reptiles (Lizards and Snakes) and Terrestrial Turtles.

Convergent evolution of oxygen transport mechanisms arises from respiratory proteins adapting to similar environmental pressures. We examined this relationship between adult hemoglobin subunits (Hbs: HBA1, HBAD, HBB1, and HBB2) found in land reptiles (lizards, snakes, and turtles) with their global distribution variables: Altitude, latitude, ambient temperature, and biomass production. We found that biomass was positively associated with the synonymous substitution rate (dS) of HBAD, while it showed the opposite trend for HBB2 in snakes. Additionally, latitude was negatively related to the dS of HBB2 in snakes, but nonsignificant with other Hbs. Altitude was negatively associated with ω = dN/dS of HBA1 and HBAD, whereas temperature showed a similar negative trend with the ω of HBAD across reptiles and in HBB2 of snakes. At amino acid sites, we found most were conserved except for 11 (two near the heme-binding pocket) across Hbs. These fast-changing sites shifted from polar to nonpolar residues, showing a pattern seen in high-altitude mammals. Our results highlight that in reptiles (i) Hbs are diversifying at individual amino acid sites while generally some subunits exhibiting lower ω rates at higher altitudes and hotter temperatures, with the later and higher biomass ecosystems also linked to increases in dS; (ii) HBBs are the most conserved of the Hbs; (iii) latitudinal gradients only show a significant association with the dS of HBB2 in snakes; and (iv) gene conversion events occurred across HBBs in reptiles, which confound their homology assignation, except for snakes that evidenced a single major duplication in their HBBs.

Animals↗

PubMed2026

Transgenerational chromosome repair in the asexual bdelloid rotifer Adineta vaga.

Homologous recombination is an essential DNA repair mechanism that also promotes chromosome pairing and ensures allele segregation during meiosis in sexual organisms. Here, we explore the dual function of homologous recombination in the bdelloid rotifer Adineta vaga, an asexual species known for its remarkable resilience to extreme genotoxic stresses. Genomic analyses reveal that A. vaga uses meiotic recombination to promote spontaneous crossovers and gene conversion during oogenesis and to repair the genome in response to DNA damage. The data also support a model of transgenerational DNA repair, termed break-induced homologous extension repair (BIHER), in which broken chromosomes are progressively restored over multiple generations. Our findings suggest that meiotic BIHER, coupled with the holocentric structure of chromosomes, may represent a key adaptation of life in extreme environments.

Animals↗

PubMed2026

Complex structural variation, phylogeny, and disease associations of the mucin pangenome.

Mucins are large glycoproteins that provide hydration and barrier function to epithelial tissues. Although genetically heterogeneous, all mucins harbor a large exon composed of variable number tandem repeats (VNTRs). Short-read sequencing has limited our understanding of mucin VNTR diversity and makes disease association studies challenging. We leverage 296 long-read phased genome assemblies to characterize 14 mucin family members, achieving ≥97% accuracy across 572 haplotypes. Phylogenetic haplogroup analysis reveals extraordinary structural heterozygosity, with MUC4 harboring the greatest allelic diversity (n=240 distinct lengths) and MUC12 the greatest size range (Δ = 55,233 bp; 23,080 amino acids). Ten mucins show significant population stratification (pFDR < 0.05). At the MUC4/MUC20 locus, we characterize higher-order structural variation, including a recurrent inversion, copy number variation, and interlocus gene conversion. Optimized genotyping achieves ≥95% haplogroup concordance across 10 loci. We apply this to 4,637 deeply phenotyped cystic fibrosis patients and identify a significant association between short MUC1 VNTRs and severe disease (p=0.0056), demonstrating the pangenome's utility for complex locus genotyping and disease discovery.

Journal Article↗

PubMed2025

De novo discovery of conserved gene clusters in microbial genomes with Spacedust.

Metagenomics has revolutionized environmental and human-associated microbiome studies. However, the limited fraction of proteins with known biological processes and molecular functions presents a major bottleneck. In prokaryotes and viruses, evolution favors keeping genes participating in the same biological processes colocalized as conserved gene clusters. Conversely, conservation of gene neighborhood indicates functional association. Here we present Spacedust, a tool for systematic, de novo discovery of conserved gene clusters. To find homologous protein matches, Spacedust uses fast and sensitive structure comparison with Foldseek. Partially conserved clusters are detected using novel clustering and order conservation P values. We demonstrate Spacedust's sensitivity with an all-versus-all analysis of 1,308 bacterial genomes, identifying 72,843 conserved gene clusters containing 58% of the 4.2 million genes. It recovered 95% of antiviral defense system clusters annotated by the specialized tool PADLOC. Spacedust's high sensitivity and speed will facilitate the annotation of large numbers of sequenced bacterial, archaeal and viral genomes.

Metagenomics↗

PubMed2026

Arabidopsis TITAN-LIKE is required for U12-type intron splicing, especially of AT-AC subtypes.

Many eukaryotes possess two types of spliceosomes: the U2-dependent and U12-dependent spliceosomes. The U2-dependent spliceosome processes >99% of all introns, whereas the U12-dependent spliceosome acts on only ~0.3% of introns, one-third of which start with AT and end with AC, with the remainder having GT-AG termini. How the U12-dependent spliceosome splices two types of introns with different terminal sequences remains poorly understood. Human centrosomal AT-AC splicing factor (CENATAC) is a subunit of the U12-dependent spliceosome that is particularly required for the splicing of the AT-AC subtype. The Arabidopsis genome contains a single homolog, TITAN-LIKE (TTL), but its function in splicing remains unknown. Here, we generated ttl mutants and isolated two viable alleles, of which we analyzed one, designated ttl-142, to investigate TTL's function in splicing. ttl-142 carries a 42-nucleotide deletion that removes 14 amino acid residues from the predicted protein, and homozygous mutants exhibit morphological abnormalities. Most U12-dependent introns were less efficiently spliced in ttl-142 than in the wild type, with the splicing of AT-AC introns particularly suppressed. Splicing suppression in ttl-142 was more extensive than in a drol1 (defective repression of the OLE3:LUC1) mutant, which carries a mutation in a gene specifically required for AT-AC intron splicing. Conversely, fewer genes showed altered expression levels in ttl-142 than in drol1, and most differentially expressed genes differed between the two mutants. These results suggest that the phenotypes of ttl-142 and drol1 mutants may reflect the impairment of distinct spliceosomal functions.

Arabidopsis↗