Origin of a new protein-coding gene de novo from non-coding sequence was
thought to be a rare event with near-zero probability. Although recently origin of de
novo protein-coding genes has attracted increasing attention, none of the reported de
novo genes has received direct evidence for its protein-coding ability and how it
functions in an organism. In this study, we identified a de novo originated gene MDF1
in Saccharomyces cerevisiae. We not only provide solid in vivo evidence for its
protein-coding ability but also clearly reveal its pathway involvement. Based on
phenotypic, genetic, cytological and biochemical evidence, we show that MDF1 can
physically bind one of the mating type determinants, MATα2 protein, and
subsequently suppress the downstream haploid-specific genes. By doing so, MDF1
decreases mating efficiency of the baker’s yeast in rich medium, which limits the cost
of mating, and consequently confers selective advantage to the species probably
through promoting vegetative growth. Our results prove that a newly generated gene
can not only associate with a fundamental pathway, but also take charge of the basic
biological process at the most upstream node. These new findings shed new lights on
several important issues including functionalization of a de novo originated gene,
evolution of pathways, and regulation of the mating pathway in the budding yeast.
Another part of this work is to study the molecular mechanism of sense-antisense
gene pair interaction. Recent transcription profiling studies have revealed an
unexpectedly large proportion of antisense transcripts in eukaryotic genomes. These
antisense genes have been implicated in the regulation of sense gene expression.
However, all the reported regulatory mechanisms including RNAi, antisense
RNA-induced histone deacetylation and transcription interference rely on the non-coding antisense RNAs, whether the protein-coding antisense gene can serve a
regulatory role remains an open question. In this study, we found that a protein
encoded by the antisense gene ADF1 binds to the promoter of the newly evolved
sense gene MDF1 and suppresses its transcription in S. cerevisiae. The sense gene
MDF1 shortens the lag phase of vegetative growth by physically interacting with
SNF1, the governing factor of nonfermentable carbon source utilization, and thus
confers selective advantage to yeasts through rapidly consuming glucose. For
avoiding the concomitant side-effects of mad growth, ADF1 takes the responsibility
of a transcription suppressor shortly after the expression level of MDF1 reaches a
peak. Together, our results not only present a new mechanism of sense-antisense
interaction, but also provide great insight on how the antagonistic gene pair makes a
concerted effort in taking maximum advantage of the changing environment.
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