Assignment for Friday:
Assignment for Monday:
Discussion of midterm grades and of sequence space.
Discuss tree of life - three domains, main endosymbiosis events, archaeplastida, other algae.
Slides on cladistics.
Introns and Their Evolution
Three groups of introns based on their splicing mechanisms:group I and II are self-splicing [have different splicing mechanism: see this figure for comparison of splicing]:
group III introns are present in eukaryotic nucleus, need spliceosomes to splice out:
Where different groups of introns occur?
- Group I: were discovered in ciliated protozoan Tetrahymena; found also in Physarum, fungal and algal mitochondria and phage T4, rare in Bacteria, one is present in Thermotoga 23SrRNA
- Group II: common in Bacteria, and so far found only in one Archaeal genus, Methanosarcina
- Spliceosomal Introns: present throughout eukaryotes, but more common in "crown-group" eukaryotes
Where do spliceosomal introns come from and how the splicing machinery evolved?
Hypothesis:Spliceosomal introns evolved from Class II introns; the function of some of the internal loops of the class II introns are taken over by the spliceosomal snRNA (small nuclear RNA).
- Group II introns are often located in intergenic regions in Bacteria, suggesting their mobility as parasitic genetic elements
- Group II and spliceosomal introns both form a lariat structure (see figures above)
- class II introns that are non-functioning because a loop has been removed splice in the presence of snRNA.
- The reverse is true too: domain of a group II intron can substitute snRNA of the spliceosome
Gratuitous complexity hypothesis for evolution of spliceosomal machinery: See reading assignment on WebCT [the portions for the reading are highlighted in the PDF file]
Problem:class II introns are found in bacteria, and only in one Archaeal genus, Methanosarcina; why is it that predominately "crown-group" eukaryotes have introns?
Not much of a splice site consensus (exon1 GT-intron-AT exon2)
Group I introns often have homing endonucleases.
Homing endonucleases and intron mobility. Spread in populations, selective pressure on endonuclease. See the excellent paper by Goddard and Burt on the reinvasion cycle.
Also: reverse splicing
Possible benefits of having introns:Exon shuffling, alternative splicing (1 gene -> different protein products) ....
Two rival hypotheses: Intron Early vs. Intron Late
Intron early:Protein diversity arose in analogy to exon shuffling in the generation of antibody diversity (see your biochemistry or genetics textbook on the maturation of the immune system).
- Introns separate structural domains. Example of a Go-plot is here (from here, these authors describe an significant excess of introns in the linker regions defined through he overlap in the Go-plot).
- Introns arose early, before the uptake of the mitochondrial and chloroplast endosymbiont,
- Neighboring introns often are in the same phase. While significant, the excess is rather small: 216 of 570, 36 more than expected under a random distribution). However, the excess is larger, if only multidomain proteins are considered, suggesting that these indeed evolved through exon shuffling (see here for a recent analysis).
Intron late:Present day introns are late invaders of already functional genes. Exon shuffling might play some role in eukaryotes, but most of protein diversity arose before introns invaded protein coding genes.
- distribution of introns mapped on phylogenetic trees unambiguously points towards late invasion (and here).
- The correlation between structure and intron position is not unambiguous.
- The finding that introns in mitochondrial (eubacterial) and nucleocytoplasmic genes have introns in the same location could reflect a preferred intron integration site. The phase pattern is also observed in vertebrate genes, in which the introns are of late origin.
- Exon shuffling requires introns located in the same phase, but there might be other reasons for having a slight excess of introns in the same phase. For introns to frequently invade genes, there needs to be mechanisms for introns to find new "homes" (see above).
Compromise:mixed model of intron evolution
- version 1 - while some introns are recent, most are old. E.g.: [Roy, 2003].
- version 2 - while most introns are recent, some are older, but not necessarily very old. E.g.: [Rogozin et al., 2003]
it was suggested that class II introns were the reason for the separation between transcription and translation in Eukaryotes (accomplished through the nuclear envelope). Martin and Koonin's hypothesis suggests that class 2 introns were brought into the eukaryotic cell by the mitochondrial endosymbiont.
Goals class 14: