The amylase gene (AMY), which codes for a starch-digesting enzyme in animals, underwent several gene copy number gains in humans (Perry et al., 2007), dogs (Axelsson et al., 2013), and mice (Schibler et al., 1982), possibly along with increased starch consumption during the evolution of these species. Here, we present comprehensive evidence for AMY copy number expansions that independently occurred in several mammalian species which consume diets rich in starch. We also provide correlative evidence that AMY gene duplications may be an essential first step for amylase to be expressed in saliva. Our findings underscore the overall importance of gene copy number amplification as a flexible and fast evolutionary mechanism that can independently occur in different branches of the phylogeny.

Sialic acids (Sia) are the primary receptors for influenza viruses and are widely displayed on cell surfaces and in secreted mucus. Sia may be present in variant forms that include O-acetyl modifications at C-4, C-7, C-8, and C-9 positions and N-acetyl or N-glycolyl at C-5. They can also vary in their linkages, including α2-3 or α2-6 linkages. Here, we analyze the distribution of modified Sia in cells and tissues of wild-type mice or in mice lacking CMP-N-acetylneuraminic acid hydroxylase (CMAH) enzyme, which synthesizes N-glycolyl (Neu5Gc) modifications. We also examined the variation of Sia forms on erythrocytes and in saliva from different animals. To determine the effect of Sia modifications on influenza A virus (IAV) infection, we tested for effects on hemagglutinin (HA) binding and neuraminidase (NA) cleavage. We confirmed that 9-O-acetyl, 7,9-O-acetyl, 4-O-acetyl, and Neu5Gc modifications are widely but variably expressed in mouse tissues, with the highest levels detected in the respiratory and gastrointestinal (GI) tracts. Secreted mucins in saliva and surface proteins of erythrocytes showed a high degree of variability in display of modified Sia between different species. IAV HAs from different virus strains showed consistently reduced binding to both Neu5Gc- and O-acetyl-modified Sia; however, while IAV NAs were inhibited by Neu5Gc and O-acetyl modifications, there was significant variability between NA types. The modifications of Sia in mucus may therefore have potent effects on the functions of IAV and may affect both pathogens and the normal flora of different mucosal sites. IMPORTANCE Sialic acids (Sia) are involved in numerous different cellular functions and are receptors for many pathogens. Sia come in chemically modified forms, but we lack a clear understanding of how they alter interactions with microbes. Here, we examine the expression of modified Sia in mouse tissues, on secreted mucus in saliva, and on erythrocytes, including those from IAV host species and animals used in IAV research. These Sia forms varied considerably among different animals, and their inhibitory effects on IAV NA and HA activities and on bacterial sialidases (neuraminidases) suggest a host-variable protective role in secreted mucus.

BackgroundA common, 32kb deletion of LCE3B and LCE3C genes is strongly associated with psoriasis. We recently found that this deletion is ancient, predating Human-Denisovan divergence. However, it was not clear why negative selection has not removed this deletion from the population.ResultsHere, we show that the haplotype block that harbors the deletion (i) retains high allele frequency among extant and ancient human populations; (ii) harbors unusually high nucleotide variation (π, P < 4.1 × 10−3); (iii) contains an excess of intermediate frequency variants (Tajima’s D, P < 3.9 × 10−3); and (iv) has an unusually long time to coalescence to the most recent common ancestor (TSel, 0.1 quantile).ConclusionsOur results are most parsimonious with the scenario where the LCE3BC deletion has evolved under balancing selection in humans. More broadly, this is consistent with the hypothesis that a balance between autoimmunity and natural vaccination through increased exposure to pathogens maintains this deletion in humans.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-016-0842-6) contains supplementary material, which is available to authorized users.

How novel gene functions evolve is a fundamental question in biology. Mucin proteins, a functionally but not evolutionarily defined group of proteins, allow the study of convergent evolution of gene function. By analyzing the genomic variation of mucins across a wide range of mammalian genomes, we propose that exonic repeats and their copy number variation contribute substantially to the de novo evolution of new gene functions. By integrating bioinformatic, phylogenetic, proteomic, and immunohistochemical approaches, we identified 15 undescribed instances of evolutionary convergence, where novel mucins originated by gaining densely O-glycosylated exonic repeat domains. Our results suggest that secreted proteins rich in proline are natural precursors for acquiring mucin function. Our findings have broad implications for understanding the role of exonic repeats in the parallel evolution of new gene functions, especially those involving protein glycosylation.

No abstract