Study Follows Modern Human Effects of Splicing Variants Originating in Archaic Hominins

Researchers from Brown University and McMaster University use archaic sequence data to retrace natural selection effects on variants influencing pre-messenger RNA splicing for a paper appearing in the Proceedings of the National Academy of Sciences. With the help of artificial genes containing Neanderthal and Denisovan sequences, the team used a massively parallel splicing reporter assay to assess the RNA splicing effects of nearly 5,200 variants, flagging 962 variants with distinct splicing roles in archaic hominins and present-day modern humans that were analyzed further using splice variant predictions and splicing quantitative trait locus profiles. Along with an apparent uptick in purifying selection on splice-altering variants in modern humans, the results highlight examples of introgressed archaic variants with potential adaptive benefits, as well as Neanderthal or Denisovan variants suspected of having pathogenic immunity or sperm maturation effects. "Our findings indicate that purifying selection acted against splicing variants in modern human populations, whereas positive selection favored splicing variants in adaptive introgression," the authors write. "By distinguishing causal from linked variants, our study contributes to understanding the functional consequences of genetic variation within extant and extinct hominins and of introgressed variation in modern human populations."