SARS‑CoV‑2 entry into and evolution within a skilled nursing facility

SARS-CoV-2 belongs to the family Coronaviridae which includes multiple human pathogens that have an outsized impact on aging populations. As a novel human pathogen, SARS-CoV-2 is undergoing continuous adaptation to this new host species and there is evidence of this throughout the scientific and public literature. However, most investigations of SARS-CoV-2 evolution have focused on largescale collections of data across diverse populations and/or living environments. Here we investigate SARS-CoV-2 evolution in epidemiologically linked individuals within a single outbreak at a skilled nursing facility beginning with initial introduction of the pathogen. The data demonstrate that SARSCoV- 2 was introduced to the facility multiple times without establishing an interfacility transmission chain, followed by a single introduction that infected many individuals within a week. This largescale introduction by a single genotype then persisted in the facility. SARS-CoV-2 sequences were investigated at both the consensus and intra-host variation levels. Understanding the variability in SARS-CoV-2 during transmission chains will assist in understanding the spread of this disease and can ultimately inform best practices for mitigation strategies

Data from: Intrinsic differences between males and females determine sex-specific consequences of inbreeding

Background Inbreeding increases homozygosity and exposes deleterious recessive alleles, generally decreasing the fitness of inbred individuals. Interestingly, males and females are usually affected differently by inbreeding, though the more vulnerable sex depends on the species and trait measured. Results We used the soil-dwelling nematode Caenorhabditis remanei to examine sex-specific inbreeding depression across nine lineages, five levels of inbreeding, and hundreds of thousands of progeny. Female nematodes consistently suffered greater fitness losses than their male counterparts, especially at high levels of inbreeding. Conclusions These results suggest that females experience stronger selection on genes contributing to reproductive traits. Inbreeding depression in males may be further reduced by sex chromosome hemizygosity, which affects the dominance of some mutations, as well as by the absence of sexual selection. Determining the relative contributions of sex-specific expression, genes on the sex chromosomes, and the environment they are filtered through—including opportunities for sexual selection—may explain the frequent though inconsistent records of sex differences in inbreeding depression, along with their implications for conservation and the evolution of mating systems

Sex-specific inbreeding on egg survivorship/hatching

Data is provided for male and female specific survivorship of eggs for different levels of inbreeding for nine different independently derived lineages. Columns give the sex of the focal individual (mated with an outbred control), the family/lineage ID, the level of inbreeding (F), the total number of eggs that were alive versus dead for a given replicate individual

Sex specific inbreeding on offspring production per day

Data is provided for male and female offspring production for different levels of inbreeding for nine different independently derived lineages. Columns give the sex of the focal individual (mated with an outbred control), the family/lineage ID, the level of inbreeding (F), and columns for the day-specific offspring production for each individual

Sex-specific inbreeding on offspring number

Data is provided for male and female offspring production for different levels of inbreeding for nine different independently derived lineages. Columns give the sex of the focal individual (mated with an outbred control), the family/lineage ID, the level of inbreeding (F), the total number of offspring produced over an individuals lifespan, and the log transformation of offspring number

Effects of inbreeding on male mating success

Data is provided for male mating success across different levels of inbreeding for nine different independently derived lineages. Columns give the family/lineage ID, the level of inbreeding (F), mating rate of the focal male (in females per hour), and the log of the mating rate

Historical trends and new surveillance of Plasmodium falciparum drug resistance markers in Angola

Background: Plasmodium falciparum resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) has historically posed a major threat to malaria control throughout the world. The country of Angola officially replaced CQ with artemisinin-based combination therapy (ACT) as a first-line treatment in 2006, but malaria cases and deaths have recently been rising. Many classic resistance mutations are relevant for the efficacy of currently available drugs, making it important to continue monitoring their frequency in Angola. Methods: Plasmodium falciparum DNA was sampled from the blood of 50 hospital patients in Cabinda, Angola from October-December of 2018. Each infection was genotyped for 13 alleles in the genes crt, mdr1, dhps, dhfr, and kelch13, which are collectively involved in resistance to six common anti-malarials. To compare frequency patterns over time, P. falciparum genotype data were also collated from studies published from across Angola in the last two decades. Results: The two most important alleles for CQ resistance, crt 76T and mdr1 86Y, were found at respective frequencies of 71.4% and 6.5%. Historical data suggest that mdr1 N86 has been steadily replacing 86Y throughout Angola in the last decade, while the frequency of crt 76T has been more variable across studies. Over a third of new samples from Cabinda were ‘quintuple mutants’ for SP resistance in dhfr/dhps, with a sixth mutation at dhps A581G present at 9.6% frequency. The markers dhfr 51I, dhfr 108N, and dhps 437G have been nearly fixed in Angola since the early 2000s, whereas dhfr 59R may have risen to high frequency more recently. Finally, no non-synonymous polymorphisms were detected in kelch13, which is involved in artemisinin resistance in Southeast Asia. Conclusions: Genetic markers of P. falciparum resistance to CQ are likely declining in frequency in Angola, consistent with the official discontinuation of CQ in 2006. The high frequency of multiple genetic markers of SP resistance is consistent with the continued public and private use of SP. In the future, more complete haplotype data from mdr1, dhfr, and dhps will be critical for understanding the changing efficacy of multiple anti-malarial drugs. These data can be used to support effective drug policy decisions in Angola

High rate of adaptation of mammalian proteins that interact with <i>Plasmodium</i> and related parasites

<div><p><i>Plasmodium</i> parasites, along with their Piroplasm relatives, have caused malaria-like illnesses in terrestrial mammals for millions of years. Several <i>Plasmodium</i>-protective alleles have recently evolved in human populations, but little is known about host adaptation to blood parasites over deeper evolutionary timescales. In this work, we analyze mammalian adaptation in ~500 <i>Plasmodium</i>- or Piroplasm- interacting proteins (PPIPs) manually curated from the scientific literature. We show that (i) PPIPs are enriched for both immune functions and pleiotropy with other pathogens, and (ii) the rate of adaptation across mammals is significantly elevated in PPIPs, compared to carefully matched control proteins. PPIPs with high pathogen pleiotropy show the strongest signatures of adaptation, but this pattern is fully explained by their immune enrichment. Several pieces of evidence suggest that blood parasites specifically have imposed selection on PPIPs. First, even non-immune PPIPs that lack interactions with other pathogens have adapted at twice the rate of matched controls. Second, PPIP adaptation is linked to high expression in the liver, a critical organ in the parasite life cycle. Finally, our detailed investigation of alpha-spectrin, a major red blood cell membrane protein, shows that domains with particularly high rates of adaptation are those known to interact specifically with <i>P</i>. <i>falciparum</i>. Overall, we show that host proteins that interact with <i>Plasmodium</i> and Piroplasm parasites have experienced elevated rates of adaptation across mammals, and provide evidence that some of this adaptation has likely been driven by blood parasites.</p></div