Biology subjects

Bergthorsson, U.

Publications and source records attributed to Bergthorsson, U..

6 recordsLinked to original sources

bioRxiv2026

No passive sidekick: mitochondrial compensatory evolution during adaptation of ETC mutant lines in Caenorhabditis elegans

Proper mitochondrial function is reliant on favourable mitonuclear epistatic interactions between two genomes, the mitochondrial (mtDNA) and the nuclear with contrasting rates of mutation, copy-number and modes of replication and transmission. The compactness and limited coding capacity of animal mtDNA along with their high mutation rates, uniparental inheritance and lack of recombination has contributed to the view that mtDNA is prone to accumulating deleterious mutations, with mitonuclear adaptation primarily attributed to the nuclear genome. Employing a prospective evolution framework in Caenorhabditis elegans, we investigated the adaptive capacity of the mtDNA in ETC-deficient lines bearing four focal ETC mutants across three different breeding systems following 60 generations of adaptation. The mtDNA genome can adapt rapidly to mitochondrial dysfunction caused by deleterious mutations in nuclear genes. Nonsynonymous changes in mtDNA protein-coding genes had significantly higher frequencies and were positively correlated with fitness, indicative of positive selection. Mitochondrial gene nd-1 emerged as a key driver of compensatory mitonuclear adaptation. Notably, compensatory mutations reach higher frequency when they affected ETC subunits in the same complex as the original deleterious mutation. Our results argue for a disproportionately outsized role for mitochondria in mitonuclear adaptation despite their diminutive genome size and protein-coding capacity.

evolutionary biology↗

bioRxiv2025

Mutational Biases and Selection in Mitochondrial Genomes: Insights from a Comparative Analysis of Natural and Experimental Populations of Caenorhabditis elegans

AO_SCPLOWBSTRACTC_SCPLOWSpontaneous mutations display biases in their relative frequencies with important consequences for genome structure and composition. While laboratory studies have provided important insights into the spontaneous mutation spectrum, laboratory environments for optimal growth may engender biases that are not representative of natural populations. We analyzed the mitochondrial genomes of 1,524 Caenorhabditis elegans natural isolates comprising 550 unique haplotypes to investigate mtDNA polymorphism in the wild. Ancestral reconstruction was used to polarize 2,464 variants (88 indels, 2,376 SNPs) and the results were compared to mutations identified in experimental lines under relaxed selection. MtDNA variant distribution in natural isolates is strongly dependent on site-degeneracy in a manner consistent with purifying selection. There is significant variation in the synonymous and nonsynonymous polymorphism between genes. Specifically, ETC complex I genes are enriched for nonsynonymous polymorphism. The probability of synonymous mutation is higher at sites with flanking G/C nucleotides and the per gene synonymous polymorphism is negatively correlated with A+T-content at the 1st and 2nd codon positions. Furthermore, the 5' and 3' ends of genes have both higher A+T-content and less synonymous polymorphism than central regions. There is evidence of natural selection for preferred codons. We identify the first cases of large heteroplasmic mtDNA structural variants in C. elegans natural isolates, comprising deletions and duplications. Although some patterns of mtDNA mutational bias are similar between laboratory and natural populations, there exist significant differences. In particular, transversions typically associated with oxidative damage are less common at four-fold degenerate sites in natural populations relative to the laboratory. SO_SCPLOWIGNIFICANCEC_SCPLOWElements of genome structure, such as base composition and DNA strand bias are in large parts caused by the spectrum of spontaneous mutations. However, laboratory estimates of the mutation spectrum can be biased in an artificial environment that favors fast growth and short generation times. Polarized synonymous and rare variants in the mitochondrial genome of 1,524 natural isolates of Caenorhabditis elegans were analyzed to test if laboratory estimates of the mutation spectrum are representative of spontaneous mutations in the wild. The genomic distribution of synonymous variants is influenced by (i) base composition differences between and within genes, and (ii) natural selection for preferred codons. Certain categories of mutations, especially G/C [->] T/A transversions, are underrepresented in natural isolates relative to laboratory experiments. This discrepancy suggests that oxidative DNA damage is not as important a source of mutations in the wild relative to laboratory populations.

evolutionary biology↗

bioRxiv2022

Bergerac Strains of C. elegans Revisited: Expansion of Tc1 elements Impose a Significant Genomic and Fitness Cost

The DNA transposon Tc1 was the first transposable element (TE) to be characterized in Caenorhabditis elegans and to date, remains the best-studied TE in Caenorhabditis worms. While Tc1 copy-number is regulated at approximately 30 copies in the laboratory N2/Bristol and the vast majority of C. elegans strains, the Bergerac strain and its derivatives have experienced a marked Tc1 proliferation. Given the historical importance of the Bergerac strain in the development of the C. elegans model, we implemented a modern genomic analysis of three Bergerac strains (CB4851, RW6999, and RW7000) in conjunction with multiple phenotypic assays to better elucidate the (i) genomic distribution of Tc1, and (ii) phenotypic consequences of TE deregulation for the host organism. The median estimates of Tc1 copy-number in the Bergerac strains ranged from 451 to 748, which is both (i) greater than previously estimated, and (ii) likely to be an underestimate of the actual copy-numbers since coverage-based estimates and ddPCR results both suggest higher Tc1 numbers. All three Bergerac strains had significantly reduced trait means compared to the N2 control for each of four fitness-related traits, with specific traits displaying significant differences between Bergerac strains. Tc1 proliferation was genome-wide, specific to Tc1, and particularly high on chromosomes V and X. There were fewer Tc1 insertions in highly expressed chromatin environments than expected by chance. Furthermore, Tc1 integration motifs were also less frequent in exon than non-coding sequences. The source of the proliferation of Tc1 in the Bergerac strains is specific to Tc1 and independent of other TEs. The Bergerac strains contain none of the alleles that have previously been found to derepress TE activity in C. elegans. However, the Bergerac strains had several Tc1 insertions near or within highly germline-transcribed genes which could account for the recent germline proliferation.

evolutionary biology↗

bioRxiv2021

Mutation rate and spectrum in Caenorhabditis elegans mutation accumulation lines subjected to RNAi-induced knockdown of the mismatch repair gene msh-2

DNA mismatch repair (MMR), an evolutionarily conserved repair pathway shared by prokaryotic and eukaryotic species alike, influences molecular evolution by detecting and correcting mismatches that escape DNA polymerase proofreading, thereby protecting genetic fidelity, reducing the mutational load, and preventing lethality. Herein we conduct the first genome-wide evaluation of the alterations to the mutation rate and spectrum under impaired activity of the MutS homolog, msh-2, in Caenorhabditis elegans. We performed mutation accumulation (MA) under RNAi-induced knockdown of msh-2 for 50 generations in obligately outcrossing fog-2(lf) lines, followed by next-generation sequencing of 19 MA lines and the ancestral control. msh-2 impairment substantially increased the frequency of nuclear base substitutions ([~]23x) and small indels ([~]328x) relative to wildtype. However, we observed no increase in the mutation rates of mtDNA, and copy-number changes of single-copy genes. There was a marked increase in copy-number variation of rDNA genes under MMR impairment. In C. elegans, msh-2 repairs transitions more efficiently than transversions as well as increases the AT mutational bias relative to wildtype. The local sequence context, including sequence complexity, G+C-content, and flanking bases influenced the mutation rate. The X chromosome had a lower substitution and higher indel rate than autosomes, which can either result from sex-specific mutation rates or a nonrandom distribution of mutable sites in the genome. Comparison of MMR impairment in C. elegans to that in other species shows that the specificity of the MMR varies between taxa, and is more efficient in detecting and repairing small indels in eukaryotes relative to prokaryotes.

evolutionary biology↗

bioRxiv2021

Global Gene Expression Divergence in Spontaneous Mutation Accumulation Lines of Caenorhabditis elegans under Varying Efficiency of Selection

To ascertain the effect of relaxation of selection on global gene expression, Caenorhabditis elegans mutation accumulation (MA) lines were propagated under varying degrees of efficiency of selection determined by their different population sizes (N = 1, 10 and 100). Both the mutational variance (Vm), and the residual variance (Vr) were greatest in MA lines with the lowest efficiency of natural selection. The results suggest that gene expression is under strong balancing selection. Furthermore, mutations resulting in increased transcriptional noise or sensitivity to microenvironmental variation accumulate most under extreme genetic drift. In contrast, the Vm/Vr ratio was lowest in the N =1 lines. Chromatin domains associated with broad gene silencing and active transcription exhibited the greatest and the smallest increase in transcriptional variation, respectively. Furthermore, the preponderance of overexpressed genes was especially pronounced in mitochondrial respiration, stress response, and immune system pathways, especially in low fitness N = 1 lines.

evolutionary biology↗

bioRxiv2019

Mutational Landscape of Spontaneous Base Substitutions and Small Indels in Experimental Caenorhabditis elegans Populations of Differing Size

Experimental investigations into the rates and fitness effects of spontaneous mutations are fundamental for our understanding of the evolutionary process. To gain insights into the molecular and fitness consequences of spontaneous mutations, we conducted a mutation accumulation (MA) experiment at varying population sizes in the nematode Caenorhabditis elegans, evolving 35 lines in parallel for 409 generations at three population sizes (N = 1, 10, 100 individuals). Here, we focus on nuclear SNPs and small indels under minimal influence of selection, as well as their accrual rates in larger populations under greater selection efficacy. The spontaneous rates of base substitutions and small indels are 1.84 x 10-9 substitutions and 6.84 x 10-10 changes /site/generation, respectively. Small indels exhibit a deletion-bias with deletions exceeding insertions by three-fold. Notably, there was no correlation between the frequency of base substitutions, nonsynonymous substitutions or small indels with population size. These results contrast with our previous analysis of mtDNA mutations and nuclear copy-number changes in these MA lines, and suggest that nuclear base substitutions and small indels are under less stringent purifying selection compared to the former mutational classes. A transition bias was observed in exons as was a near universal base substitution bias towards A/T. Strongly context-dependent base substitutions, where 5-T and 3-As increase the frequency of A/T [->] T/A transversions, especially at the boundaries of A or T homopolymeric runs, manifest as higher mutation rates in (i) introns and intergenic regions relative to exons, (ii) chromosomal cores versus arms and tips, and (iii) germline-expressed genes.

evolutionary biology↗