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Hidden Markov models representing 167 protein sequence families were used to infer the presence or absence of homologs within the transcriptomes of 183 algal species/strains. Statistical analyses of the distribution of HMM hits across major clades of algae, or at branch points on the phylogenetic tree of 98 chlorophytes, confirmed and extended known cases of metabolic loss and gain, most notably the loss of the mevalonate pathway for terpenoid synthesis in green algae but not, as we show here, in the streptophyte algae. Evidence for novel events was found as well, most remarkably in the recurrent and coordinated gain or loss of enzymes for the glyoxylate shunt. We find, as well, a curious pattern of retention (or re-gain) of HMG-CoA synthase in chlorophytes that have otherwise lost the mevalonate pathway, suggesting a novel, co-opted function for this enzyme in select lineages. Finally, we find striking, phylogenetically linked distributions of coding sequences for three pathways that synthesize the major membrane lipid phosphatidylcholine, and a complementary phylogenetic distribution pattern for the non-phospholipid DGTS (diacyl-glyceryl-trimethylhomoserine). Mass spectrometric analysis of lipids from 25 species was used to validate the inference of DGTS synthesis from sequence data.

Many algae produce triacylglycerides (TAG) when starved for assimilable nitrogen. In the model organism Chlamydomonas reinhardtii , and probably in other species, nitrogen starvation is also the cue to prepare for sexual reproduction. The ensuing process of gametogenesis entails a host of physiological and gene expression changes, which makes it difficult to distinguish the changes that are peculiar to TAG accumulation from other aspects of gametogenesis. As others have found, we show here that the chlorophyte Ettlia oleoabundans produces TAG under conditions of nitrogen deprivation and elevated NaCl concentrations. We exploit these two conditions, and the intermediate response of the organism to intermediate levels of stress, to identify physiological and gene regulatory features in common. Strikingly, TAG levels and chlorophyll concentrations are inversely correlated across both sets of conditions. Similarly, membrane lipids undergo related compositional changes under the two conditions. In contrast, RNA-seq analysis reveals substantially different expression profiles. This is useful because the gene expression changes that are in common, against this background of expression differences, are more likely to be relevant to the shared changes in physiology and lipid composition. Gene expression changes in common include transcripts related to fatty acid synthesis and degradation, TAG synthesis, and a putative TAG lipase that is substantially down-regulated. The identification of properties that are shared by distinct TAG-inducing conditions could facilitate the engineering of algal strains with improved TAG production properties.

Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions or deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic diversity by three ethnicities in Singapore and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese ∼24,800 years ago and experienced significant admixture with East Asians ∼1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, 14 of which harbored robust associations with complex traits and diseases. Finally, we show that our data can substantially improve genotype imputation in diverse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) National Research Foundation (NRF) Accepted version We acknowledge H.M. Kang, S. Das, A. Tan, F. Zhang, J. Terhorst, P.-R. Loh, and G. Hellenthal for helpful discussions and support from all participants and clinical research coordinators of the contributing cohorts and studies: the TTSH Healthy Control Workgroup, the SEED cohort, the Asian Sudden Cardiac Death in Heart Failure Study, the Singapore Heart Failure Outcomes and Phenotypes (SHOP) cohort, the Asian neTwork for Translational Research and Cardiovascular Trials (ATTRaCT), the Parkinson’s Disease Study, the Peranakan Genome Study, the Platinum Asian Genomes Project, the Bariatric Surgery Study, the National Heart Centre Singapore Biobank and SingHEART cohorts, and the GUSTO and S-PRESTO study groups. This study was supported by Singapore’s A*STAR (core funding and IAF-PP H17/01/a0/007), BMRC (SPF2014/001, SPF2013/002, SPF2014/003, SPF2014/004, and SPF2014/005), NMRC (CIRG/1371/2013, CIRG/1417/2015, CIRG/1488/ 2018, CSA-SI/0012/2017, CG/017/2013, CG/M006/2017_NHCS, TCR/013- NNI/2014, STaR/0011/2012, STaR2013/001, STaR/014/2013, STaR/0026/ 2015, TCR/006-NUHS/2013, TCR/012-NUHS/2014, TCR/004-NUS/2008, TCR/012-NUHS/2014, and center grants 2010-13 and 2013-2017), NRF (NRFF2016-03), National University of Singapore, SingHealth and DukeNUS, and Alexandra Health small innovative grant SIGII/15203 and funding from Huazhong University of Science and Technology, the Tanoto Foundation, the Lee Foundation, the Boston Scientific Investigator Sponsored Research Program and Bayer, the NSF (DEB-1753489), and the Alfred P. Sloan Foundation. The computation was partially performed on resources of the National Supercomputing Centre, Singapore (https://www.nscc.sg).

The sex drive hypothesis predicts that stronger selection on male traits has resulted in masculinization of the genome. Here we test whether such masculinizing effects can be detected at the level of the transcriptome and methylome in the adult zebrafish brain. Although methylation is globally similar, we identified 914 specific differentially methylated CpGs (DMCs) between males and females (435 were hypermethylated and 479 were hypomethylated in males compared to females). These DMCs were prevalent in gene body, intergenic regions and CpG island shores. We also discovered 15 distinct CpG clusters with striking sex-specific DNA methylation differences. In contrast, at transcriptome level, more female-biased genes than male-biased genes were expressed, giving little support for the male sex drive hypothesis. Our study provides genome-wide methylome and transcriptome assessment and sheds light on sex-specific epigenetic patterns and in zebrafish for the first time.