Where the minor things are: a pan-eukaryotic survey suggests neutral processes may explain much of minor intron evolution

Abstract

Spliceosomal introns are gene segments removed from RNA transcripts by ribonucleoprotein machineries called spliceosomes. In some eukaryotes a second ‘minor’ spliceosome is responsible for processing a tiny minority of introns. Despite its seemingly modest role, minor splicing has persisted for roughly 1.5 billion years of eukaryotic evolution. Identifying minor introns in over 3000 eukaryotic genomes, we report diverse evolutionary histories including surprisingly high numbers in some fungi and green algae, repeated loss, as well as general biases in their positional and genic distributions. We estimate that ancestral minor intron densities were comparable to those of vertebrates, suggesting a trend of long-term stasis. Finally, three findings suggest a major role for neutral processes in minor intron evolution. First, highly similar patterns of minor and major intron evolution contrast with both functionalist and deleterious model predictions. Second, observed functional biases among minor intron-containing genes are largely explained by these genes’ greater ages. Third, no association of intron splicing with cell proliferation in a minor intron-rich fungus suggests that regulatory roles are lineage-specific and thus cannot offer a general explanation for minor splicing’s persistence. These data constitute the most comprehensive view of minor introns and their evolutionary history to date, and provide a foundation for future studies of these remarkable genetic elements.

Evolutionary genomics of the emergence of brown algae as key components of coastal ecosystems

“…On average, brown algal genes tend to be more intron-rich than those of the other stramenopile groups 15 , including closely-related sister species (Figure 2B), with the notable exception of Chrysoparadoxa australica , whose genes contain many short, C/T-rich introns (Figure 2B). The vast majority of splice sites in Phaeophyceae are of the canonical GT-AG type and no signatures of minor U12 introns were identified in intronic sequences, in accordance with a previous study 16 . Consistent with this observation, an analysis of spliceosome proteins using a recent reference dataset 17 found that, with the exception of ZCRB1, none of the 12 minor spliceosome genes were present in brown algal genomes (Table S3), indicating that the minor intron spliceosomal associated machinery was lost in the Phaeophyceae.…”

Structural basis of U12-type intron engagement by the fully assembled human minor spliceosome

“…These interactions provide a structural basis for the conservation of the minor intron 5′SS. The 5′ nucleotide of the U12-type 5′SS may be either A1 or G1 ( 30 , 31 ). In our structure, the 6′ NH 2 of A1 makes a putative H-bond to the carbonyl oxygen of Gly 17 from U11-35K.…”

A TALS-likeRTTNmutation impedes neural rosette formation in human cortical organoids

“…RNU4ATAC is a non-coding gene transcribed into the small nuclear RNA (snRNA) U4atac, a component of the minor spliceosome. This ribonucleic complex excises less than one percent of all human introns, 12 and deficiency in its function leads in most cases to minor intron retention that impairs the correct maturation of about 750 minor-intron containing transcripts. 2,[13][14][15][16][17] Here, we report a particular case of a patient with TALS traits but no variant in RNU4ATAC.…”