Comparative study of human mitochondrial proteome reveals extensive protein subcellular relocalization after gene duplications.
BACKGROUND
Gene and genome duplication is the principle creative force in evolution. Recently, protein subcellular relocalization, or neolocalization was proposed as one of the mechanisms responsible for the retention of duplicated genes. This hypothesis received support from the analysis of yeast genomes, but has not been tested thoroughly on animal genomes. In order to evaluate the importance of subcellular relocalizations for retention of duplicated genes in animal genomes, we systematically analyzed nuclear encoded mitochondrial proteins in the human genome by reconstructing phylogenies of mitochondrial multigene families.


RESULTS
The 456 human mitochondrial proteins selected for this study were clustered into 305 gene families including 92 multigene families. Among the multigene families, 59 (64%) consisted of both mitochondrial and cytosolic (non-mitochondrial) proteins (mt-cy families) while the remaining 33 (36%) were composed of mitochondrial proteins (mt-mt families). Phylogenetic analyses of mt-cy families revealed three different scenarios of their neolocalization following gene duplication: 1) relocalization from mitochondria to cytosol, 2) from cytosol to mitochondria and 3) multiple subcellular relocalizations. The neolocalizations were most commonly enabled by the gain or loss of N-terminal mitochondrial targeting signals. The majority of detected subcellular relocalization events occurred early in animal evolution, preceding the evolution of tetrapods. Mt-mt protein families showed a somewhat different pattern, where gene duplication occurred more evenly in time. However, for both types of protein families, most duplication events appear to roughly coincide with two rounds of genome duplications early in vertebrate evolution. Finally, we evaluated the effects of inaccurate and incomplete annotation of mitochondrial proteins and found that our conclusion of the importance of subcellular relocalization after gene duplication on the genomic scale was robust to potential gene misannotation.


CONCLUSIONS
Our results suggest that protein subcellular relocalization is an important mechanism for the retention and gain of function of duplicated genes in animal genome evolution.
Wang
Xiujuan
X
Interdepartmental Genetics Program, Iowa State University, Ames, IA 50011, USA. xiujuan@iastate.edu
Huang
Yong
Y
Lavrov
Dennis V
DV
Gu
Xun
X
D000818:Animals; D055028:Comparative Genomic Hybridization; D004272:DNA, Mitochondrial / Q000235:genetics; D019143:Evolution, Molecular; D020440:Gene Duplication; D015894:Genome, Human; D054629:Genome, Mitochondrial; D006801:Humans; D016013:Likelihood Functions; D024101:Mitochondrial Proteins / Q000235:genetics; D005810:Multigene Family; D010802:Phylogeny; D020543:Proteome / Q000235:genetics*; D020539:Sequence Analysis, Protein
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D020543:Proteome