Functional diversification of duplicate genes through subcellular adaptation of encoded proteins

Analysis of the subcellular localization patterns of duplicate genes revealed that protein subcellular adaptation represents a common mechanism for the functional diversification of duplicate genes

Emergence of Young Human Genes after a Burst of Retroposition in Primates

The origin of new genes through gene duplication is fundamental to the evolution of lineage- or species-specific phenotypic traits. In this report, we estimate the number of functional retrogenes on the lineage leading to humans generated by the high rate of retroposition (retroduplication) in primates. Extensive comparative sequencing and expression studies coupled with evolutionary analyses and simulations suggest that a significant proportion of recent retrocopies represent bona fide human genes. We estimate that at least one new retrogene per million years emerged on the human lineage during the past ∼63 million years of primate evolution. Detailed analysis of a subset of the data shows that the majority of retrogenes are specifically expressed in testis, whereas their parental genes show broad expression patterns. Consistently, most retrogenes evolved functional roles in spermatogenesis. Proteins encoded by X chromosome−derived retrogenes were strongly preserved by purifying selection following the duplication event, supporting the view that they may act as functional autosomal substitutes during X-inactivation of late spermatogenesis genes. Also, some retrogenes acquired a new or more adapted function driven by positive selection. We conclude that retroduplication significantly contributed to the formation of recent human genes and that most new retrogenes were progressively recruited during primate evolution by natural and/or sexual selection to enhance male germline function

Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome

A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations

Distribution of the proportion of shared interactors for genes in S- and D-pairs

<p><b>Copyright information:</b></p><p>Taken from "Functional diversification of duplicate genes through subcellular adaptation of encoded proteins"</p><p>http://genomebiology.com/2008/9/3/R54</p><p>Genome Biology 2008;9(3):R54-R54.</p><p>Published online 12 Mar 2008</p><p>PMCID:PMC2397506.</p><p></p

Illustration of the different evolutionary fates of (functional) duplicate genes

Each gene/protein is represented in different colors: red, ancestral, 'A'; green, duplicate copy A1; and blue, duplicate copy A2. Different shapes of proteins (circle, square, and triangle) indicate different functions. Three different subcellular localizations (nucleus, cytoplasm, and cytoplasmic membrane) are indicated in a schematic cell. We note that only the major possible scenarios are illustrated here.<p><b>Copyright information:</b></p><p>Taken from "Functional diversification of duplicate genes through subcellular adaptation of encoded proteins"</p><p>http://genomebiology.com/2008/9/3/R54</p><p>Genome Biology 2008;9(3):R54-R54.</p><p>Published online 12 Mar 2008</p><p>PMCID:PMC2397506.</p><p></p

Distribution of non-synonymous substitution rates () for duplicate genes in S- and D-pairs (estimated for the time since the whole-genome duplication event - see text for details)

<p><b>Copyright information:</b></p><p>Taken from "Functional diversification of duplicate genes through subcellular adaptation of encoded proteins"</p><p>http://genomebiology.com/2008/9/3/R54</p><p>Genome Biology 2008;9(3):R54-R54.</p><p>Published online 12 Mar 2008</p><p>PMCID:PMC2397506.</p><p></p

Subcellular localizations of the UBC and AIR family members and subcellular localization changes inferred based on the phylogeny

The common name and yeast protein identifier (in brackets) of the protein are indicated. The schematic representation of a yeast cell depicts three possible localizations: nucleus (small circle), endoplasmatic reticulum (eclipse around nucleus), and cytoplasm (remainder of the cell). The co-localization of the protein with one of the yeast subcellular compartments is indicated by grey shading.<p><b>Copyright information:</b></p><p>Taken from "Functional diversification of duplicate genes through subcellular adaptation of encoded proteins"</p><p>http://genomebiology.com/2008/9/3/R54</p><p>Genome Biology 2008;9(3):R54-R54.</p><p>Published online 12 Mar 2008</p><p>PMCID:PMC2397506.</p><p></p