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Nonadaptive Amino Acid Convergence Rates Decrease over Time.

ABSTRACT: Convergence is a central concept in evolutionary studies because it provides strong evidence for adaptation. It also provides information about the nature of the fitness landscape and the repeatability of evolution, and can mislead phylogenetic inference. To understand the role of adaptive convergence, we need to understand the patterns of nonadaptive convergence. Here, we consider the relationship between nonadaptive convergence and divergence in mitochondrial and model proteins. Surprisingly, nonadaptive convergence is much more common than expected in closely related organisms, falling off as organisms diverge. The extent of the convergent drop-off in mitochondrial proteins is well predicted by epistatic or coevolutionary effects in our "evolutionary Stokes shift" models and poorly predicted by conventional evolutionary models. Convergence probabilities decrease dramatically if the ancestral amino acids of branches being compared have diverged, but also drop slowly over evolutionary time even if the ancestral amino acids have not substituted. Convergence probabilities drop-off rapidly for quickly evolving sites, but much more slowly for slowly evolving sites. Furthermore, once sites have diverged their convergence probabilities are extremely low and indistinguishable from convergence levels at randomized sites. These results indicate that we cannot assume that excessive convergence early on is necessarily adaptive. This new understanding should help us to better discriminate adaptive from nonadaptive convergence and develop more relevant evolutionary models with improved validity for phylogenetic inference.

SUBMITTER: Goldstein RA

PROVIDER: S-EPMC4572784 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Nonadaptive Amino Acid Convergence Rates Decrease over Time.

Goldstein Richard A RA Pollard Stephen T ST Shah Seena D SD Pollock David D DD

Molecular biology and evolution 20150303 6

Convergence is a central concept in evolutionary studies because it provides strong evidence for adaptation. It also provides information about the nature of the fitness landscape and the repeatability of evolution, and can mislead phylogenetic inference. To understand the role of adaptive convergence, we need to understand the patterns of nonadaptive convergence. Here, we consider the relationship between nonadaptive convergence and divergence in mitochondrial and model proteins. Surprisingly, ...[more]

PMID: 25737491

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Project description:ImportanceDespite the proliferation of pharmacy standing-order naloxone dispensing across many US states before the change to over-the-counter status, few policy analyses have evaluated the implementation of pharmacy naloxone standing orders in addressing opioid overdose fatality among communities.ObjectiveTo determine whether the implementation of pharmacy standing-order naloxone was associated with lower opioid fatality rates compared with communities without pharmacies with standing-order naloxone.Design, setting, and participantsThis retrospective multisite study was conducted with an interrupted time series analysis across 351 municipalities in Massachusetts over 24 quarters (from January 1, 2013, through December 31, 2018). Standing-order naloxone dispensing data were collected from 2 sources for all major chain pharmacies and many independent pharmacies, covering 70% of retail pharmacies in Massachusetts. Municipalities had various standing-order naloxone implementation inceptions during the study period. Data were analyzed from December 2021 to November 2023.ExposureThe main exposure was measured by the first quarter with standing-order naloxone dispensation as the actual implementation inception.Main outcomes and measuresThe primary study outcome was municipal opioid fatality rate per 100 000 population obtained from the Massachusetts Registry of Vital Records and Statistics.ResultsThe median (IQR) population size across 351 municipalities was 10 314 (3635 to 21 781) people, with mean (SD) proportion of female individuals was 51.1% (2.8 percentage points). Pharmacies from 214 municipalities (60.9%) reported dispensing standing-order naloxone over the study period. At the baseline of the first quarter of 2013, municipalities that eventually had standing-order naloxone had greater quarterly opioid fatality rates compared with those that never implemented standing-order naloxone (3.51 vs 1.03 deaths per 100 000 population; P < .001). After adjusting for municipal-level sociodemographic and opioid prevention factors, there was significant slope decrease of opioid fatality rates (annualized rate ratio, 0.84; 95% CI, 0.78-0.91; P < .001) following standing-order naloxone dispensing, compared with the municipalities that did not implement standing-order naloxone. There were no significant level changes of opioid fatality rates in the adjusted models. Sensitivity analyses yielded similar and significant findings.Conclusions and relevanceThese findings suggest that community pharmacy dispensing of naloxone with standing orders was associated with a relative, gradual, and significant decrease in opioid fatality rates compared with communities that did not implement the standing-order naloxone program. These findings support the expansion of naloxone access, including over-the-counter naloxone as part of a multifaceted approach to address opioid overdose.

Dataset Information

Nonadaptive Amino Acid Convergence Rates Decrease over Time.

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Nonadaptive Amino Acid Convergence Rates Decrease over Time.

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