Evolution of enzyme levels in metabolic pathways: A theoretical approach. Part 2

Metabolism is essential for cell function and adaptation. Because of their central role in metabolism, kinetic parameters and enzyme concentrations are under constant selective pressure to adapt the fluxes of the metabolic networks to the needs of the organism. In the line of various studies dealing with enzyme evolution, we recently developed a model of evolution of enzyme concentrations under selection for increased flux, considered as a proxy of fitness (Coton 2021). Taking into account two realistic cellular constraints, competition for resources and co-regulations, we determined the evolutionary equilibria and the ranges of neutral variations of enzyme concentrations. In this article, we give more generality to this model, by considering that the enzymes of a pathway can belong to different groups of co-regulation. We determined the equilibria and showed that the constraints modify the adaptive landscape by limiting the number of independent dimensions. We also showed that any trade-off between enzyme concentration is sufficient to limit the flux and to relax selection for increasing other enzyme concentrations. Even though the model is based on simplifying assumptions, the complexity of the relationship between enzyme concentrations prevents the analysis of selective neutrality.

Admixture with indigenous people helps local adaptation: admixture-enabled selection in Polynesians

Background Homo sapiens have experienced admixture many times in the last few thousand years. To examine how admixture affects local adaptation, we investigated genomes of modern Polynesians, who are shaped through admixture between Austronesian-speaking people from Southeast Asia (Asian-related ancestors) and indigenous people in Near Oceania (Papuan-related ancestors). Methods In this study local ancestry was estimated across the genome in Polynesians (23 Tongan subjects) to find the candidate regions of admixture-enabled selection contributed by Papuan-related ancestors. Results The mean proportion of Papuan-related ancestry across the Polynesian genome was estimated as 24.6% (SD = 8.63%), and two genomic regions, the extended major histocompatibility complex (xMHC) region on chromosome 6 and the ATP-binding cassette transporter sub-family C member 11 (ABCC11) gene on chromosome 16, showed proportions of Papuan-related ancestry more than 5 SD greater than the mean (> 67.8%). The coalescent simulation under the assumption of selective neutrality suggested that such signals of Papuan-related ancestry enrichment were caused by positive selection after admixture (false discovery rate = 0.045). The ABCC11 harbors a nonsynonymous SNP, rs17822931, which affects apocrine secretory cell function. The approximate Bayesian computation indicated that, in Polynesian ancestors, a strong positive selection (s = 0.0217) acted on the ancestral allele of rs17822931 derived from Papuan-related ancestors. Conclusions Our results suggest that admixture with Papuan-related ancestors contributed to the rapid local adaptation of Polynesian ancestors. Considering frequent admixture events in human evolution history, the acceleration of local adaptation through admixture should be a common event in humans.

The maintenance of standing genetic variation: gene flow versus selective neutrality in Atlantic stickleback fish

Adaptation to derived habitats often occurs from standing genetic variation (SGV). The maintenance within ancestral populations of genetic variants favorable in derived habitats is commonly ascribed to long-term antagonism between purifying selection and gene flow resulting from hybridization across habitats. A largely unexplored alternative idea based on quantitative genetic models of polygenic adaptation is that variants favored in derived habitats are neutral in ancestral populations when their frequency is relatively low. To explore the latter, we first identify genetic variants important to the adaptation of threespine stickleback fish to a rare derived habitat – nutrient-depleted acidic lakes – based on whole-genome sequence data. Sequencing marine stickleback from six locations across the Atlantic ocean then allows us to infer that the frequency of these derived variants in the ancestral habitat is unrelated to the likely opportunity for gene flow of these variants from acidic-adapted populations. This result is consistent with the selective neutrality of derived variants within the ancestor. Our study thus supports an underappreciated explanation for the maintenance of SGV, and calls for a better understanding of the fitness consequences of adaptive genetic variation across habitats and genomic backgrounds.

On the Distribution of Tract Lengths During Adaptive Introgression

Admixture is increasingly being recognized as an important factor in evolutionary genetics. The distribution of genomic admixture tracts, and the resulting effects on admixture linkage disequilibrium, can be used to date the timing of admixture between species or populations. However, the theory used for such prediction assumes selective neutrality despite the fact that many famous examples of admixture involve natural selection acting for or against admixture. In this paper, we investigate the effects of positive selection on the distribution of tract lengths. We develop a theoretical framework that relies on approximating the trajectory of the selected allele using a logistic function. By numerically calculating the expected allele trajectory, we also show that the approach can be extended to cases where the logistic approximation is poor due to the effects of genetic drift. Using simulations, we show that the model is highly accurate under most scenarios. We use the model to show that positive selection on average will tend to increase the admixture tract length. However, perhaps counter-intuitively, conditional on the allele frequency at the time of sampling, positive selection will actually produce shorter expected tract lengths. We discuss the consequences of our results in interpreting the timing of the introgression of EPAS1 from Denisovans into the ancestors of Tibetans.

Genetic variability and population structure of Capoeta gracilis (Keyserling 1861) populations in the southern basin rivers of the Caspian Sea as revealed by the mtDNA sequences

This study investigated the genetic structure and diversity of Capoeta gracilis (Keyserling 1861) from the southern basin of the Caspian Sea employing cytochrome b gene sequence analysis. For this purpose, a total of 83 specimens of this species were sampled and analysed from four rivers viz., CheshmeKile, Siahrood, Tajan and ZarrinGol. Nucleotide diversity ranged from 0.00030 to 0.00715 and haplotype diversity from 0.27895 to 0.68421 for the populations studied. A total of 14 haplotypes were obtained and haplotype no. 2 was shared by all. Pairwise FST analysis showed that there was a significant genetic difference between the populations studied, with the exception of the populations living in the Siahrood and Tajan rivers. Analysis of molecular variance (AMOVA) also confirmed the genetic differentiation among populations showing 76.03% of the genetic variation within populations and 23.97% among populations (p<0.01). A selective neutrality test showed that populations of C. gracilis were probably in equilibrium and were not experiencing a population expansion. In general, it can be said that distinct populations of this species are living in the rivers of northern Iran, though further studies using other genes and molecular markers are needed to confirm the findings.

Considering Genomic Scans for Selection as Coalescent Model Choice

First inspired by the seminal work of Lewontin and Krakauer (1973. Distribution of gene frequency as a test of the theory of the selective neutrality of polymorphisms. Genetics 74(1):175–195.) and Maynard Smith and Haigh (1974. The hitch-hiking effect of a favourable gene. Genet Res. 23(1):23–35.), genomic scans for positive selection remain a widely utilized tool in modern population genomic analysis. Yet, the relative frequency and genomic impact of selective sweeps have remained a contentious point in the field for decades, largely owing to an inability to accurately identify their presence and quantify their effects—with current methodologies generally being characterized by low true-positive rates and/or high false-positive rates under many realistic demographic models. Most of these approaches are based on Wright–Fisher assumptions and the Kingman coalescent and generally rely on detecting outlier regions which do not conform to these neutral expectations. However, previous theoretical results have demonstrated that selective sweeps are well characterized by an alternative class of model known as the multiple-merger coalescent. Taken together, this suggests the possibility of not simply identifying regions which reject the Kingman, but rather explicitly testing the relative fit of a genomic window to the multiple-merger coalescent. We describe the advantages of such an approach, which owe to the branching structure differentiating selective and neutral models, and demonstrate improved power under certain demographic scenarios relative to a commonly used approach. However, regions of the demographic parameter space continue to exist in which neither this approach nor existing methodologies have sufficient power to detect selective sweeps.

Selection-Driven Gene Inactivation in Salmonella

Bacterial genes are sometimes found to be inactivated by mutation. This inactivation may be observable simply because selection for function is intermittent or too weak to eliminate inactive alleles quickly. Here, I investigate cases in Salmonella enterica where inactivation is instead positively selected. These are identified by a rate of introduction of premature stop codons to a gene that is higher than expected under selective neutrality, as assessed by comparison to the rate of synonymous changes. I identify 84 genes that meet this criterion at a 10% false discovery rate. Many of these genes are involved in virulence, motility and chemotaxis, biofilm formation, and resistance to antibiotics or other toxic substances. It is hypothesized that most of these genes are subject to an ongoing process in which inactivation is favored under rare conditions, but the inactivated allele is deleterious under most other conditions and is subsequently driven to extinction by purifying selection.

On the distribution of tract lengths during adaptive introgression

ABSTRACTAdmixture is increasingly being recognized as an important factor in evolutionary genetics. The distribution of genomic admixture tracts, and the resulting effects on admixture linkage disequilibrium, can be used to date the timing of admixture between species or populations. However, the theory used for such prediction assumes selective neutrality despite the fact that many famous examples of admixture involve natural selection acting for or against admixture. In this paper, we investigate the effects of positive selection on the distribution of tract lengths. We develop a theoretical framework that relies on approximating the trajectory of the selected allele using a logistic function. By numerically calculating the expected allele trajectory, we also show that the approach can be extended to cases where the logistic approximation is poor due to the effects of genetic drift. Using simulations, we show that the model is highly accurate under most scenarios. We use the model to show that positive selection on average will tend to increase the admixture tract length. However, perhaps counter-intuitively, conditional on the allele frequency at the time of sampling, positive selection will actually produce shorter expected tract lengths. We discuss the consequences of our results in interpreting the timing of the introgression of EPAS1 from Denisovans into the ancestors of Tibetans.