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Pathogens found within local environments are a major cause of morbidity and mortality. This is particularly true in Indonesia, where infectious diseases such as malaria or dengue are a significant part of the disease burden within the country. One way to strengthen the control of infectious diseases is through better surveillance, however unequal investment in medical funding throughout Indonesia, particularly in rural areas, has resulted in under-reporting of cases. Here, we use transcriptome data from 117 healthy individuals living on the islands of Mentawai, Sumba, and the Indonesian side of New Guinea Island to explore which pathogens are present within whole blood. We are able to detect a broad range of taxa within RNA-sequencing data generated from whole blood, including bacteria, viruses, archaea, and eukaryotes. Using independent component analysis, we find that two of these pathogens—Flaviviridae and Plasmodium—have the most noticeable effects on expression profiles. We also identify specific genes linked with Plasmodium and Flavivirus abundance and find that both of these infections are most pronounced in the easternmost island within our Indonesian dataset. This study provides a framework for novel applications of RNA-seq as surveillance and a better understanding of environmental contributors affecting gene expression within Indonesia.

Human pygmy populations inhabit different regions of the world, from Africa to Melanesia. In Asia, short-statured populations are often referred to as "negritos." Their short stature has been interpreted as a consequence of thermoregulatory, nutritional, and/or locomotory adaptations to life in tropical forests. A more recent hypothesis proposes that their stature is the outcome of a life history trade-off in high-mortality environments, where early reproduction is favored and, consequently, early sexual maturation and early growth cessation have coevolved. Some serological evidence of deficiencies in the growth hormone/insulin-like growth factor axis have been previously associated with pygmies' short stature. Using genome-wide single-nucleotide polymorphism genotype data, we first tested whether different negrito groups living in the Philippines and Papua New Guinea are closely related and then investigated genomic signals of recent positive selection in African, Asian, and Papuan pygmy populations. We found that negritos in the Philippines and Papua New Guinea are genetically more similar to their nonpygmy neighbors than to one another and have experienced positive selection at different genes. These results indicate that geographically distant pygmy groups are likely to have evolved their short stature independently. We also found that selection on common height variants is unlikely to explain their short stature and that different genes associated with growth, thyroid function, and sexual development are under selection in different pygmy groups.

Malaria is one of the leading causes of illness and death globally. The vast majority of transcriptomic studies of the impact of malaria on human hosts have been conducted on populations of African ancestry suffering from Plasmodium falciparum infection, making it unclear whether biological responses observed in these studies can be generalised to other populations. Here, we perform differential expression analysis between healthy controls and malaria-infected patients within Indonesia, a country of over 260 million people which has substantial morbidity due to endemic malaria. We find that in samples infected with P. falciparum and P. vivax, there is an upregulation of genes involved in inflammation, the immediate early immune response, translation, and apoptosis. When comparing these findings to transcriptomic studies conducted in Africa (on P. falciparum) and South America (on P. vivax), we find that many pathways are shared. This is particularly apparent for receptor recognition and inflammation-related genes in P. falciparum and innate immune and chemokine-related genes in P. vivax infection. However, we also find that many genes are unique to the Indonesian population, particularly those involved in RNA processing, splicing, and cell surface receptor genes. This study provides a more comprehensive view of malaria infection outside of Africa and contributes to a better characterisation of malaria pathogenesis within humans across a range of genetic architectures.