The rapidly growing database of completely sequenced genomes of bacteria, archaea and eukaryotes (over 500 genomes available by the middle of 2004 and many more in progress) creates both new opportunities and new challenges for genome research. During the last year, we performed several studies that took advantage of the genomic information to establish fundamental principles of genome evolution and function. In particualr, we proposed a new type of rare genomic changes (RGCs) designated RGC_CAMs (after Conserved Amino acids-Multiple substitutions), which are inferred using a genome-scale analysis of protein and underlying nucleotide sequence alignments. The RGC_CAM approach utilizes amino acid residues conserved in major eukaryotic lineages, with the exception of a few species comprising a putative clade, and selects for phylogenetic inference only those amino acid replacements that require 2 or 3 nucleotide substitutions, in order to reduce homoplasy. The RGC_CAM analysis was combined with a procedure for rigorous statistical testing of competing phylogenetic hypotheses. The RGC_CAM method was shown to be robust to branch length differences and taxon sampling. When applied to animal phylogeny, the RGC_CAM approach strongly supports the coelomate clade that unites chordates with arthropods as opposed to the ecdysozoan (molting animals) clade. This conclusion runs against the view of animal evolution that is currently prevailing in the evo-devo community. It is expected that RGC_CAM and other RGC-based methods will be crucial for these future, definitive phylogenetic studies. In another major study, we examined the selective forces that affect synonymous positions during the evolution of mammalian genes.? Evolution of protein sequences is largely governed by purifying selection, with a small fraction of proteins evolving under positive selection. The evolution at synonymous positions in protein-coding genes is not nearly as well understood, with the extent and types of selection remaining, largely, unclear. A statistical test to identify purifying and positive selection at synonymous sites in protein-coding genes was developed. The method compares the rate of evolution at synonymous sites (Ks) to that in intron sequences of the same gene after sampling the aligned intron sequences to mimic the statistical properties of coding sequences. We detected purifying selection at synonymous sites in approximately 28% of the 1,562 analyzed orthologous genes from mouse and rat, and positive selection in approximately 12% of the genes. Thus, the fraction of genes with readily detectable positive selection at synonymous sites is much greater than the fraction of genes with comparable positive selection at nonsynonymous sites, i.e., at the level of the protein sequence. Unlike other genes, the genes with positive selection at synonymous sites showed no correlation between Ks and the rate of evolution in nonsynonymous sites (Ka), indicating that evolution of synonymous sites under positive selection is decoupled from protein evolution. The genes with purifying selection at synonymous sites showed significant anticorrelation between Ks and expression level and breadth, indicating that highly expressed genes evolve slowly. The genes with positive selection at synonymous sites showed the opposite trend, i.e., highly expressed genes had, on average, higher Ks. For the genes with positive selection at synonymous sites, a significantly lower mRNA stability is predicted compared to the genes with negative selection. Thus, mRNA destabilization could be an important factor driving positive selection in nonsynonymous sites, probably, through regulation of expression at the level of mRNA degradation and, possibly, also translation rate. So, unexpectedly, we found that positive selection at synonymous sites of mammalian genes is substantially more common than positive selection at the level of protein sequences. We propose that positive selection at synonymous sites might act through mRNA destabilization affecting mRNA levels and translation.

Agency
National Institute of Health (NIH)
Institute
National Library of Medicine (NLM)
Type
Intramural Research (Z01)
Project #
1Z01LM000073-12
Application #
7594463
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2007
Total Cost
$617,886
Indirect Cost
Name
National Library of Medicine
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Ivankov, Dmitry N; Payne, Samuel H; Galperin, Michael Y et al. (2013) How many signal peptides are there in bacteria? Environ Microbiol 15:983-90
Rogozin, Igor B; Carmel, Liran; Csuros, Miklos et al. (2012) Origin and evolution of spliceosomal introns. Biol Direct 7:11
Mulkidjanian, Armen Y; Bychkov, Andrew Yu; Dibrova, Daria V et al. (2012) Open questions on the origin of life at anoxic geothermal fields. Orig Life Evol Biosph 42:507-16
Denoeud, France; Henriet, Simon; Mungpakdee, Sutada et al. (2010) Plasticity of animal genome architecture unmasked by rapid evolution of a pelagic tunicate. Science 330:1381-5
Lee, Renny C H; Gill, Erin E; Roy, Scott W et al. (2010) Constrained intron structures in a microsporidian. Mol Biol Evol 27:1979-82
Basu, Malay Kumar; Poliakov, Eugenia; Rogozin, Igor B (2009) Domain mobility in proteins: functional and evolutionary implications. Brief Bioinform 10:205-16
Koonin, Eugene V; Senkevich, Tatiana G; Dolja, Valerian V (2009) Compelling reasons why viruses are relevant for the origin of cells. Nat Rev Microbiol 7:615; author reply 615
Koonin, E V; Wolf, Y I; Puigbò, P (2009) The phylogenetic forest and the quest for the elusive tree of life. Cold Spring Harb Symp Quant Biol 74:205-13
Mulkidjanian, Armen Y; Galperin, Michael Y; Koonin, Eugene V (2009) Co-evolution of primordial membranes and membrane proteins. Trends Biochem Sci 34:206-15
Makarova, Kira S; Wolf, Yuri I; Koonin, Eugene V (2009) Comprehensive comparative-genomic analysis of type 2 toxin-antitoxin systems and related mobile stress response systems in prokaryotes. Biol Direct 4:19

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