Understanding the patterns and causes of protein sequence evolution is a major challenge in evolutionary biology. One of the critical unresolved issues is the relative contribution of selection and ...genetic drift to the fixation of amino acid sequence differences between species. Molecular homoplasy, the independent evolution of the same amino acids at orthologous sites in different taxa, is one potential signature of selection; however, relatively little is known about its prevalence in eukaryotic proteomes. To quantify the extent and type of homoplasy among evolving proteins, we used phylogenetic methodology to analyze 8 genome-scale data matrices from clades of different evolutionary depths that span the eukaryotic tree of life. We found that the frequency of homoplastic amino acid substitutions in eukaryotic proteins was more than 2-fold higher than expected under neutral models of protein evolution. The overwhelming majority of homoplastic substitutions were parallelisms that involved the most frequently exchanged amino acids with similar physicochemical properties and that could be reached by a single-mutational step. We conclude that the role of homoplasy in shaping the protein record is much larger than generally assumed, and we suggest that its high frequency can be explained by both weak positive selection for certain substitutions and purifying selection that constrains substitutions to a small number of functionally equivalent amino acids.
Organisms cope with physiological stressors through acclimatizing mechanisms in the short-term and adaptive mechanisms over evolutionary timescales. During adaptation to an environmental or genetic ...perturbation, beneficial mutations can generate numerous physiological changes: some will be novel with respect to prior physiological states, while others might either restore acclimatizing responses to a wild-type state, reinforce them further, or leave them unchanged. We examined the interplay of acclimatizing and adaptive responses at the level of global gene expression in Methylobacterium extorquens AM1 engineered with a novel central metabolism. Replacing central metabolism with a distinct, foreign pathway resulted in much slower growth than wild-type. After 600 generations of adaptation, however, eight replicate populations founded from this engineered ancestor had improved up to 2.5-fold. A comparison of global gene expression in wild-type, engineered, and all eight evolved strains revealed that the vast majority of changes during physiological adaptation effectively restored acclimatizing processes to wild-type expression states. On average, 93% of expression perturbations from the engineered strain were restored, with 70% of these occurring in perfect parallel across all eight replicate populations. Novel changes were common but typically restricted to one or a few lineages, and reinforcing changes were quite rare. Despite this, cases in which expression was novel or reinforced in parallel were enriched for loci harboring beneficial mutations. One case of parallel, reinforced changes was the pntAB transhydrogenase that uses NADH to reduce NADP(+) to NADPH. We show that PntAB activity was highly correlated with the restoration of NAD(H) and NADP(H) pools perturbed in the engineered strain to wild-type levels, and with improved growth. These results suggest that much of the evolved response to genetic perturbation was a consequence rather than a cause of adaptation and that physiology avoided "reinventing the wheel" by restoring acclimatizing processes to the pre-stressed state.
Natural selection is generally expected to favor one form of a given trait within a population. The presence of multiple functional variants of traits involved in activities such as feeding, ...reproduction, or the defense against predators is relatively uncommon within animal species. The genetic architecture and evolutionary mechanisms underlying the origin and maintenance of such polymorphisms are of special interest. Among rattlesnakes, several instances of the production of biochemically distinct neurotoxic or hemorrhagic venom types within the same species are known. Here, we investigated the genetic basis of this phenomenon in three species and found that neurotoxic and hemorrhagic individuals of the same species possess markedly different haplotypes at two toxin gene complexes. For example, neurotoxic and hemorrhagic Crotalus scutulatus individuals differ by 5 genes at the phospholipase A2 (PLA2) toxin gene complex and by 11 genes at the metalloproteinase (MP) gene complex. A similar set of extremely divergent haplotypes also underlies alternate venom types within C. helleri and C. horridus. We further show that the MP and PLA2 haplotypes of neurotoxic C. helleri appear to have been acquired through hybridization with C. scutulatus—a rare example of the horizontal transfer of a potentially highly adaptive suite of genes. These large structural variants appear analogous to immunity gene complexes in host-pathogen arms races and may reflect the impact of balancing selection at the PLA2 and MP complexes for predation on different prey.
•Members of some rattlesnake species produce either hemorrhagic or neurotoxic venoms•This polymorphism is due to variation in toxin gene number at two gene complexes•Neurotoxin genes were transferred into one rattlesnake species by hybridization
Individuals within several rattlesnake species produce alternative types of venoms composed of distinct neurotoxins or hemorrhagic metalloproteinases. Dowell et al. show that haplotypes differing by 5–11 genes at two gene complexes encode these alternative venom types, which may be maintained by balancing selection for predation on different prey.
The universal appeal and pedagogical power of stories are well established, yet they are underutilized in biology classrooms. I suggest that stories have an important role in helping students ...understand how science is made, and in offering glimpses into the hearts and lives of scientists.
Development of cardiovascular disease (CVD) remains a public health concern for young to middle‐aged adults, now exacerbated by the increasing prevalence of obesity and sedentary lifestyles. ...Cardiorespiratory fitness (CRF) improves the reclassification of short‐term (10‐year) CVD risk, but has not been uniformly defined across studies. This study evaluated cross‐sectional differences in short‐term and lifetime CVD risk scores, across both absolute metabolic equivalent (MET) and sex‐ and age‐standardized CRF categories in 805 apparently healthy young to middle‐aged adults (68% male; 47.4 ± 7.2 years). CVD risk factors were evaluated, and estimated cardiorespiratory fitness (CRF) measurements (METS and peak VO2) were derived from a submaximal Bruce treadmill test. CRF measures also included post‐exercise heart rate recovery (HRR) data. Consistent trends showing more favorable risk factor profiles and lower short‐term CVD (QRISK2), and CVD mortality (SCORE) scores, associated with higher levels of CRF were evident in both sexes. Lifetime CVD risk (Q‐Lifetime) was highest in the lowest CRF categories. Peak VO2 and HRR following submaximal exercise testing contributed to the variability in short‐term and lifetime CVD risk. Global CVD risk predictions were examined across different contemporary CRF classifications with inconsistent findings. Recommended absolute MET and sex‐ and age‐standardized CRF categories were significantly associated with both short‐term and lifetime risk of CVD outcomes. However, compared to internationally derived normative CRF standards, cohort‐specific CRF categories resulted in markedly different proportion of individuals classified in the “poor” CRF category at higher CVD risk.
Co-option occurs when natural selection finds new uses for existing traits,
including genes, organs, and other body structures. Genes can be co-opted to
generate developmental and physiological ...novelties by changing their patterns
of regulation, by changing the functions of the proteins they encode, or both.
This often involves gene duplication followed by specialization of the
resulting paralogous genes into particular functions. A major role for gene
co-option in the evolution of development has long been assumed, and many
recent comparative developmental and genomic studies have lent support to this
idea. Although there is relatively less known about the molecular basis of
co-option events involving developmental pathways, much can be drawn from
well-studied examples of the co-option of structural proteins. Here, we
summarize several case studies of both structural gene and developmental
genetic circuit co-option and discuss how co-option may underlie major episodes
of adaptive change in multicellular organisms. We also examine the phenomenon
of intraspecific variability in gene expression patterns, which we propose to
be one form of material for the co-option process. We integrate this
information with recent models of gene family evolution to provide a framework
for understanding the origin of co-optive evolution and the mechanisms by which
natural selection promotes evolutionary novelty by inventing new uses for the
genetic toolkit.
Homeotic (Hox) genes code for principal transcriptional regulators of animal body regionalization. The duplication and divergence of Hox genes, changes in their regulation, and changes in the ...regulation of Hox target genes have all been implicated in the evolution of animal diversity. It is not known whether Hox proteins have also acquired new activities during the evolution of specific lineages. Amino-acid sequences outside the DNA-binding homeodomains of Hox orthologues diverge significantly. These sequence differences may be neutral with respect to protein function, or they could be involved in the functional divergence of Hox proteins and the evolutionary diversification of animals. Here, we identify a transcriptional repression domain in the carboxy-terminal region of the Drosophila Ultrabithorax (Ubx) protein. This domain is highly conserved among Ubx orthologues in other insects, but is absent from Ubx in other arthropods and onychophorans. The evolution of this domain may have facilitated the greater morphological diversification of posterior thoracic and anterior abdominal segments characteristic of modern insects.
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