PT  - JOURNAL ARTICLE
AU  - Jiyun M. Moon
AU  - David M. Aronoff
AU  - John A. Capra
AU  - Patrick Abbot
AU  - Antonis Rokas
TI  - Genes involved in human sialic acid biology do not harbor signatures of recent positive selection
AID  - 10.1101/137034
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 137034
4099  - http://biorxiv.org/content/early/2017/05/11/137034.short
4100  - http://biorxiv.org/content/early/2017/05/11/137034.full
AB  - Sialic acids are nine carbon sugars ubiquitously found on the surfaces of vertebrate cells and are involved in various immune response-related processes; the overall diversity of sialic acids is often referred to as the host “sialome”. In humans, at least 58 genes spanning diverse functions, from biosynthesis and activation to recycling and degradation, are involved in sialic acid biology. Several sialome genes have experienced higher rates of non-synonymous substitutions in the human lineage than their counterparts in other great apes, which may be indicative of ancient positive selection in response to pathogens. To test whether sialome genes have also experienced more recent positive selection in human populations, reflecting adaptation to contemporary cosmopolitan or geographically-restricted pathogens, we calculated several metrics that quantify changes in allele frequency spectra caused by recent selection on the protein-coding and putative enhancer regions of 55 sialome genes using whole genome sequencing data of 2,504 humans from five ethnic groups. To disentangle the effects of demography, we compared the observed patterns in sialome putative enhancer regions and genes to those of 189 housekeeping genes and their putative enhancer regions, which are known to be evolving under strong negative selection due to functional constraints. We found that the patterns of genetic variation of sialome genes and putative enhancers do not differ significantly from those of their housekeeping counterparts. Furthermore, the observed patterns of genetic variation were not significantly different among the four functional categories of sialome genes. These results suggest that the genic and putative enhancer regions of sialome genes have experienced strong purifying selection but not recent positive selection. We propose that the absence of signatures of recent positive selection is consistent with the view that human sialome genes regulate immune responses against ancient rather than contemporary cosmopolitan or geographically-restricted pathogens.