The major histocompatibility complex (MHC) is an important genomic region for adaptive immunity and has long been studied in ecological and evolutionary contexts, such as disease resistance and mate and kin selection. The MHC has been investigated extensively in mammals and birds but far less so in squamate reptiles, the third major radiation of amniotes. We localized the core MHC genomic region in two squamate species, the green anole (Anolis carolinensis) and brown anole (A. sagrei), and provide the first detailed characterization of the squamate MHC, including the presence and ordering of known MHC genes in these species and comparative assessments of genomic structure and composition in MHC regions. We find that the Anolis MHC, located on chromosome 2 in both species, contains homologs of many previously-identified mammalian MHC genes in a single core MHC region. The repetitive element composition in anole MHC regions was similar to those observed in mammals but had important distinctions, such as higher proportions of DNA transposons. Moreover, longer introns and intergenic regions result in a much larger squamate MHC region (11.7 Mb and 24.6 Mb in the green and brown anole, respectively). Evolutionary analyses of MHC homologs of anoles and other representative amniotes uncovered generally monophyletic relationships between species-specific homologs and a loss of the peptide-binding domain exon 2 in one of two mhc2β gene homologs of each anole species. Signals of diversifying selection in each anole species was evident across codons of mhc1, many of which appear functionally relevant given known structures of this protein from the green anole, chicken, and human. Altogether, our investigation fills a major gap in understanding of amniote MHC diversity and evolution and provides an important foundation for future squamate-specific or vertebrate-wide investigations of the MHC.

Streptococcus pneumoniae is a leading cause of ocular infections including serious and sight-threatening conditions. The use of pneumococcal conjugate vaccines (PCV) has substantially reduced the incidence of pneumonia and invasive pneumococcal diseases, but has had limited impact on ocular infections. Additionally, widespread vaccine use has resulted in ongoing selective pressure and serotype replacement in carriage and disease. To gain insight into the population structure of pneumococcal isolates causing ocular infections in a post-PCV-13 time period, we investigated the genomic epidemiology of ocular S. pneumoniae isolates (n=45) collected at Massachusetts Eye and Ear between 2014 and 2017. By performing a series of molecular typing methods from draft genomes, we found that the population structure of ocular S. pneumoniae is highly diverse with 27 sequence types (grouped into 18 clonal complexes) and 17 serotypes being identified. Distribution of these lineages diverged according to the site of isolation, with conjunctivitis being commonly caused by isolates grouped in the Epidemic Conjunctivitis Cluster-ECC (60 %), and ST448 (53.3 %) being most frequently identified. Conversely, S. pneumoniae keratitis cases were caused by a highly diverse population of isolates grouping within 15 different clonal complexes. Serotyping inference demonstrated that 95.5 % of the isolates were non-PCV-13 vaccine types. Most of the conjunctivitis isolates (80 %) were unencapsulated, with the remaining belonging to serotypes 15B, 3 and 23B. On the other hand, S. pneumoniae causing keratitis were predominantly encapsulated (95.2 %) with 13 different serotypes identified, mostly being non-vaccine types. Carriage of macrolide resistance genes was common in our ocular S. pneumoniae population (42.2 %), and usually associated with the mefA +msrD genotype (n=15). These genes were located in the Macrolide Efflux Genetic Assembly cassette and were associated with low-level in vitro resistance to 14- and 15-membered macrolides. Less frequently, macrolide-resistant isolates carried an ermB gene (n=4), which was co-located with the tetM gene in a Tn-916-like transposon. Our study demonstrates that the population structure of ocular S. pneumoniae is highly diverse, mainly composed by isolates that escape the PCV-13 vaccine, with patterns of tissue/niche segregation, adaptation and specialization. These findings suggest that the population structure of ocular pneumococcus may be shaped by multiple factors including PCV-13 selective pressure, microbial-related and niche-specific host-associated features.

Purpose of review: Residual cardiovascular disease risk and increasing metabolic syndrome risk underscores a need for novel therapeutics targeting lipid metabolism in humans. Unbiased human genetic screens have proven powerful in identifying novel genomic loci, and this review discusses recent developments in such discovery. Recent findings: Recent human genome-wide association studies have been completed in incredibly large, detailed cohorts, allowing for the identification of >300 genomic loci that participate in regulation of plasma lipid metabolism. However, the discovery of these loci has greatly outpaced the elucidation of the underlying functional mechanisms. The identification of novel roles for long noncoding RNAs such as CHROME, LeXis, and MeXis, in lipid metabolism suggests that noncoding RNAs should be included in functional translation of GWAS loci. Summary: Unbiased genetic studies appear to have unearthed a great deal of novel biology with respect to lipid metabolism, yet translation of these findings into actionable mechanisms has been slow. Increased focus on the translation, rather than the discovery, of these loci, with new attention paid to lncRNAs, can help spur the development of novel therapeutics targeting lipid metabolism.