NMD and the evolution of eukaryotic gene structure

• All cells are confronted with undesirable transcripts derived from mutant alleles, but the production of aberrant transcripts from otherwise normal DNA may be an even greater challenge. The substantial fraction of problematical transcripts containing premature termination codons (PTCs) are subject to elimination by the nonsense-mediated mRNA decay (NMD) pathway. Phylogenetic analysis suggests that NMD and the exon junction complex (EJC) upon which it depends in mammals (see chapter by Maquat) are ancient, raising the possibility of an early association of NMD with introns. This may help explain why introns were able to proliferate to an apparently considerable degree in the stem eukaryote, despite the mutational burden that introns impose upon their host genes. A long-term evolutionary asso- ciation between NMD and introns also provides a possible explanation for the nonrandom spatial distribution of introns in the genes of multicellular species and for an apparent slow- down (and possible stabilization) of intron colonization in modern species. Several lineages, all of which are nearly devoid of ancestral introns, appear to have lost NMD and the EJC, and these taxa have exceptionally simple genomic features that minimize the chances of producing erroneous transcripts. Validation of these ideas will require empirical work on the degree of coordination between NMD, the EJC, and the locations of introns in a wide array of genes distributed across diverse phylogenetic lineages. 

Ämnesord

NATURVETENSKAP  -- Biologi -- Evolutionsbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Evolutionary Biology (hsv//eng)

Publikations- och innehållstyp

ref (ämneskategori)

kap (ämneskategori)