Life in Arctic Environments: Molecular Adaptation of Oxygen-Carrying Proteins

Abstract A central objective in biology is to link adaptive evolution in a gene to structural and/or functional phenotypic novelties. Yet most analytic methods make inferences mainly from either phenotypic data or genetic data alone. A small number of models have been developed to infer correlations between the rate of molecular evolution and changes in a discrete or continuous life history trait. But such correlations are not necessarily evidence of adaptation. Here, we present a novel approach called the phenotype–genotype branch-site model (PG-BSM) designed to detect evidence of adaptive codon evolution associated with discrete-state phenotype evolution. An episode of adaptation is inferred under standard codon substitution models when there is evidence of positive selection in the form of an elevation in the nonsynonymous-to-synonymous rate ratio $\omega$ to a value $\omega > 1$. As it is becoming increasingly clear that $\omega > 1$ can occur without adaptation, the PG-BSM was formulated to infer an instance of adaptive evolution without appealing to evidence of positive selection. The null model makes use of a covarion-like component to account for general heterotachy (i.e., random changes in the evolutionary rate at a site over time). The alternative model employs samples of the phenotypic evolutionary history to test for phenomenological patterns of heterotachy consistent with specific mechanisms of molecular adaptation. These include 1) a persistent increase/decrease in $\omega$ at a site following a change in phenotype (the pattern) consistent with an increase/decrease in the functional importance of the site (the mechanism); and 2) a transient increase in $\omega$ at a site along a branch over which the phenotype changed (the pattern) consistent with a change in the site’s optimal amino acid (the mechanism). Rejection of the null is followed by post hoc analyses to identify sites with strongest evidence for adaptation in association with changes in the phenotype as well as the most likely evolutionary history of the phenotype. Simulation studies based on a novel method for generating mechanistically realistic signatures of molecular adaptation show that the PG-BSM has good statistical properties. Analyses of real alignments show that site patterns identified post hoc are consistent with the specific mechanisms of adaptation included in the alternate model. Further simulation studies show that the covarion-like component of the PG-BSM plays a crucial role in mitigating recently discovered statistical pathologies associated with confounding by accounting for heterotachy-by-any-cause. [Adaptive evolution; branch-site model; confounding; mutation-selection; phenotype–genotype.]

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The Effects of Hill-Robertson Interference Between Weakly Selected Mutations on Patterns of Molecular Evolution and Variation

Genetics ◽

10.1093/genetics/155.2.929 ◽

2000 ◽

Vol 155 (2) ◽

pp. 929-944 ◽

Cited By ~ 14

Author(s):

Gilean A T McVean ◽

Brian Charlesworth

Keyword(s):

Codon Bias ◽

Molecular Adaptation ◽

Weak Selection ◽

Multiple Loci ◽

Locus Model ◽

Fitness Consequences ◽

Novel Variants ◽

Population Sizes ◽

The Hill ◽

Reversible Mutation

Abstract Associations between selected alleles and the genetic backgrounds on which they are found can reduce the efficacy of selection. We consider the extent to which such interference, known as the Hill-Robertson effect, acting between weakly selected alleles, can restrict molecular adaptation and affect patterns of polymorphism and divergence. In particular, we focus on synonymous-site mutations, considering the fate of novel variants in a two-locus model and the equilibrium effects of interference with multiple loci and reversible mutation. We find that weak selection Hill-Robertson (wsHR) interference can considerably reduce adaptation, e.g., codon bias, and, to a lesser extent, levels of polymorphism, particularly in regions of low recombination. Interference causes the frequency distribution of segregating sites to resemble that expected from more weakly selected mutations and also generates specific patterns of linkage disequilibrium. While the selection coefficients involved are small, the fitness consequences of wsHR interference across the genome can be considerable. We suggest that wsHR interference is an important force in the evolution of nonrecombining genomes and may explain the unexpected constancy of codon bias across species of very different census population sizes, as well as several unusual features of codon usage in Drosophila.

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Functional and Molecular Adaptation of Cl-/HCO3- Exchanger to Chronic Alkaline Media in RenalCells

Cellular Physiology and Biochemistry ◽

10.1159/000089853 ◽

2005 ◽

Vol 16 (4-6) ◽

pp. 271-280 ◽

Cited By ~ 4

Author(s):

Valeria Rivarola ◽

Paula Ford ◽

Osvaldo Chara ◽

Mario Parisi ◽

Claudia Capurro

Keyword(s):

Alkaline Media ◽

Molecular Adaptation

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Molecular Adaptation in the Lactose Operon

Control of Metabolic Processes ◽

10.1007/978-1-4757-9856-2_35 ◽

1990 ◽

pp. 389-398 ◽

Cited By ~ 1

Author(s):

Antony M. Dean

Keyword(s):

Molecular Adaptation ◽

Lactose Operon

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Molecular adaptation in adipose tissue in response to overfeeding with a high-fat diet under sedentary conditions in South Asian and Caucasian men

British Journal Of Nutrition ◽

10.1017/s0007114519001260 ◽

2019 ◽

Vol 122 (03) ◽

pp. 241-251

Author(s):

Siti N. Wulan ◽

Freek G. Bouwman ◽

Klaas R. Westerterp ◽

Edwin C. M. Mariman ◽

Guy Plasqui

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

South Asian ◽

High Fat Diet ◽

South Asians ◽

Molecular Adaptation ◽

Body Fat Percentage ◽

High Fat ◽

Fat Percentage ◽

Caucasian Men

AbstractFor the same BMI, South Asians have a higher body fat percentage than Caucasians. There might be differences in the fatty acid (FA) handling in adipose tissue when both ethnicities are exposed to high-fat overfeeding. The objective of the present study was to investigate the molecular adaptation in relation to FA metabolism in response to overfeeding with a high-fat diet (OHFD) in South Asian and Caucasian men. Ten South Asian men (BMI 18–29 kg/m2) and ten Caucasian men (BMI 22–33 kg/m2), matched for body fat percentage, aged 20–40 years were included. A weight-maintenance diet (30 % fat, 55 % carbohydrate and 15 % protein) was given for 3 d followed by 3 d of overfeeding (150 % energy requirement) with a high-fat diet (60 % fat, 25 % carbohydrate and 15 % protein) while staying in a respiration chamber. Before and after overfeeding, abdominal subcutaneous fat biopsies were taken. Proteins were isolated, analysed and quantified for short-chain 3-hydroxyacyl-CoA dehydrogenase (HADH), carnitine palmitoyl-transferase 1α (CPT1a), adipose TAG lipase, perilipin A (PLINA), perilipin B, lipoprotein lipase and fatty acid binding protein 4 using Western blotting. OHFD decreased the HADH level (P < 0·05) in Caucasians more than in Asians (P < 0·05), but the baseline and after intervention HADH level was relatively higher in Caucasians. The level of CPT1a decreased in South Asians and increased in Caucasians (P < 0·05). PLINA did not change with diet but the level was higher in South Asians (P < 0·05). The observed differences in HADH and PLINA levels as well as in CPT1a response may be important for differences in the long-term regulation of energy (fat) metabolism in these populations.

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Insertions and deletions trigger adaptive walks in Drosophila proteins

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2011.2571 ◽

2012 ◽

Vol 279 (1740) ◽

pp. 3075-3082 ◽

Cited By ~ 11

Author(s):

Evgeny V. Leushkin ◽

Georgii A. Bazykin ◽

Alexey S. Kondrashov

Keyword(s):

Amino Acid ◽

Amino Acid Sequences ◽

Molecular Adaptation ◽

Amino Acid Substitutions ◽

Protein Coding ◽

Evolution Of Life ◽

High Fraction ◽

Adaptive Walks ◽

The Difference ◽

Almost All

Maps that relate all possible genotypes or phenotypes to fitness—fitness landscapes—are central to the evolution of life, but remain poorly known. An insertion or a deletion (indel) of one or several amino acids constitutes a substantial leap of a protein within the space of amino acid sequences, and it is unlikely that after such a leap the new sequence corresponds precisely to a fitness peak. Thus, one can expect an indel in the protein-coding sequence that gets fixed in a population to be followed by some number of adaptive amino acid substitutions, which move the new sequence towards a nearby fitness peak. Here, we study substitutions that occur after a frame-preserving indel in evolving proteins of Drosophila . An insertion triggers 1.03 ± 0.75 amino acid substitutions within the protein region centred at the site of insertion, and a deletion triggers 4.77 ± 1.03 substitutions within such a region. The difference between these values is probably owing to a higher fraction of effectively neutral insertions. Almost all of the triggered amino acid substitutions can be attributed to positive selection, and most of them occur relatively soon after the triggering indel and take place upstream of its site. A high fraction of substitutions that follow an indel occur at previously conserved sites, suggesting that an indel substantially changes selection that shapes the protein region around it. Thus, an indel is often followed by an adaptive walk of length that is in agreement with the theory of molecular adaptation.

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