Papers by Federico Hoffmann
Genome Biology and Evolution
Globin-X (GbX) is an enigmatic member of the vertebrate globin gene family with a wide phyletic d... more Globin-X (GbX) is an enigmatic member of the vertebrate globin gene family with a wide phyletic distribution that spans protostomes and deuterostomes. Unlike canonical globins such as hemoglobins and myoglobins, functional data suggest that GbX does not have a primary respiratory function. Instead, evidence suggests that the monomeric, membrane-bound GbX may play a role in cellular signaling or protection against the oxidation of membrane lipids. Recently released genomes from key vertebrates provide an excellent opportunity to address questions about the early stages of the evolution of GbX in vertebrates. We integrate bioinformatics, synteny, and phylogenetic analyses to characterize the diversity of GbX genes in non-teleost ray-finned fishes, resolve relationships between the GbX genes of cartilaginous fish and bony vertebrates, and demonstrate that the GbX genes of cyclostomes and gnathostomes derive from independent duplications. Our study highlights the role that whole-genome ...
PiRNAs are a particular type of small non-coding RNA. They are distinct from miRNA in size as wel... more PiRNAs are a particular type of small non-coding RNA. They are distinct from miRNA in size as well as other characteristics, such as the lack of sequence conservation and increased complexity when compared to their miRNA counterparts. PiRNA is considered the largest class of sRNA that is expressed especially in the animal cells. piRNAs are derived from long single-stranded RNAs, which are transcribed from genomic clusters, in contrast to other small silencing RNAs. It has been speculated that one locus could generate more than one piRNA. PiRNA corresponding to repetitive elements is fewer in mammals than in other species like Drosophila and Danio rerio, which signifies that piRNA might have possessed or gained some additional functionality in mammals. While the functionality of piRNAs may not be fully understood, they are believed to be involved in gene silencing. In this paper, we will examine a novel approach to identify potential piRNA clusters based on genes downstream and upstr...
Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many... more Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.
F1000posters, Mar 22, 2012
Gene, Jan 15, 2016
Genes related to human diseases should be natural targets for evolutionary studies, since they co... more Genes related to human diseases should be natural targets for evolutionary studies, since they could provide clues regarding the genetic bases of pathologies and potential treatments. Here we studied the evolution of the reprimo gene family, a group of tumor-suppressor genes that are implicated in p53-mediated cell cycle arrest. These genes, especially the reprimo duplicate located on human chromosome 2, have been associated with epigenetic modifications correlated with transcriptional silencing and cancer progression. We demonstrate the presence of a third reprimo lineage that, together with the reprimo and reprimo-like genes, appears to have been differentially retained during the evolutionary history of vertebrates. We present evidence that these reprimo lineages originated early in vertebrate evolution and expanded as a result of the two rounds of whole genome duplications that occurred in the last common ancestor of vertebrates. The reprimo gene has been lost in birds, and the ...
Mol Biol Evol, 2007
Gene duplication is thought to play an important role in the co-option of existing protein functi... more Gene duplication is thought to play an important role in the co-option of existing protein functions to new physiological pathways. The globin superfamily of genes provides an excellent example of the kind of physiological versatility that can be attained through the functional and regulatory divergence of duplicated genes that encode different subunit polypeptides of the tetrameric hemoglobin protein. In contrast to prevailing views about the evolutionary history of the aglobin gene family, here we present phylogenetic evidence that the a A -and a D -globin genes are not the product of a single, tandem duplication of an ancestral globin gene with adult function in the common ancestor of extant birds, reptiles, and mammals. Instead, our analysis reveals that the a D -globin gene of amniote vertebrates arose via duplication of an embryonic a-like globin gene that predated the radiation of tetrapods. The important evolutionary implication is that the distinct biochemical properties of a D -hemoglobin (HbD) are not exclusively derived characters that can be attributed to a post-duplication process of neofunctionalization. Rather, many of the distinct biochemical properties of HbD are retained ancestral characters that reflect the fact that the a D -globin gene arose via duplication of a gene that had a larval/embryonic function. These insights into the evolutionary origin of HbD illustrate how adaptive modifications of physiological pathways may result from the retention and opportunistic co-option of ancestral protein functions. . Thus, regulatory
Mol Biol Evol, 2008
Species differences in the size or membership composition of multigene families can be attributed... more Species differences in the size or membership composition of multigene families can be attributed to lineage-specific additions of new genes via duplication, losses of genes via deletion or inactivation, and the creation of chimeric genes via domain shuffling or gene fusion. In principle, it should be possible to infer the recombinational pathways responsible for each of these different types of genomic change by conducting detailed comparative analyses of genomic sequence data. Here, we report an attempt to unravel the complex evolutionary history of the b-globin gene family in a taxonomically diverse set of rodent species. The main objectives were: 1) to characterize the genomic structure of the b-globin gene cluster of rodents; 2) to assign orthologous and paralogous relationships among duplicate copies of b-like globin genes; and 3) to infer the specific recombinational pathways responsible for gene duplications, gene deletions, and the creation of chimeric fusion genes. Results of our comparative genomic analyses revealed that variation in gene family size among rodent species is mainly attributable to the differential gain and loss of later expressed b-globin genes via unequal crossing-over. However, two distinct recombinational mechanisms were implicated in the creation of chimeric fusion genes. In muroid rodents, a chimeric c/e fusion gene was created by unequal crossing-over between the embryonic eand c-globin genes. Interestingly, this c/e fusion gene was generated in the same fashion as the ''anti-Lepore'' 5#-d-(b/d)-b-3# duplication mutant in humans (the reciprocal exchange product of the pathological hemoglobin Lepore deletion mutant). By contrast, in the house mouse, Mus musculus, a chimeric b/d fusion pseudogene was created by a b-globin / d-globin gene conversion event. Although the c/e and b/d fusion genes share a similar chimeric gene structure, they originated via completely different recombinational pathways.
Mol Biol Evol, 2010
The aand b-globin gene families of jawed vertebrates have diversified with respect to both gene f... more The aand b-globin gene families of jawed vertebrates have diversified with respect to both gene function and the developmental timing of gene expression. Phylogenetic reconstructions of globin gene family evolution have provided suggestive evidence that the developmental regulation of hemoglobin synthesis has evolved independently in multiple vertebrate lineages. For example, the embryonic b-like globin genes of birds and placental mammals are not 1:1 orthologs. Despite the similarity in developmental expression profiles, the genes are independently derived from lineage-specific duplications of a b-globin pro-ortholog. This suggests the possibility that other vertebrate taxa may also possess distinct repertoires of globin genes that were produced by repeated rounds of lineage-specific gene duplication and divergence. Until recently, investigations into this possibility have been hindered by the dearth of genomic sequence data from nonmammalian vertebrates. Here, we report new insights into globin gene family evolution that were provided by a phylogenetic analysis of vertebrate globins combined with a comparative genomic analysis of three key sauropsid taxa: a squamate reptile (anole lizard, Anolis carolinensis), a passeriform bird (zebra finch, Taeniopygia guttata), and a galliform bird (chicken, Gallus gallus). The main objectives of this study were 1) to characterize evolutionary changes in the size and membership composition of the aand b-globin gene families of tetrapod vertebrates and 2) to test whether functional diversification of the globin gene clusters occurred independently in different tetrapod lineages. Results of our comparative genomic analysis revealed several intriguing patterns of gene turnover in the globin gene clusters of different taxa. Lineagespecific differences in gene content were especially pronounced in the b-globin gene family, as phylogenetic reconstructions revealed that amphibians, lepidosaurs (as represented by anole lizard), archosaurs (as represented by zebra finch and chicken), and mammals each possess a distinct independently derived repertoire of b-like globin genes. In contrast to the ancient functional diversification of the a-globin gene cluster in the stem lineage of tetrapods, the physiological division of labor between early-and late-expressed genes in the b-globin gene cluster appears to have evolved independently in several tetrapod lineages.
The Open Evolution Journal, Apr 24, 2009
South American tuco-tucos (genus Ctenomys) and related coruros (genus Spalacopus), North American... more South American tuco-tucos (genus Ctenomys) and related coruros (genus Spalacopus), North American pocket gophers (family Geomyidae), and African mole rats (family Bathyergidae) are lineages of rodents that colonized the subterranean niche independently. An energetically demanding lifestyle, coupled with the hypoxic atmosphere characteristic of the subterranean environment may change the selective regime of genes that encode proteins involved in cellular respiration. Here, we examined the molecular evolution of the cytochome b gene, a mitochondrially-encoded gene participating in oxidative phosphorylation, in these lineages and their above-ground relatives. Using maximum-likelihood and Bayesian approaches, we estimated rates of synonymous (dS) and nonsynonymous (dN) substitutions. We found a significantly higher ratio (dN/dS) in each of the subterranean groups with respect to their non-subterranean counterparts. Using an alternative procedure that tests for positive selection on quantitative physicochemical amino acid properties, we found that i) subterranean mole rats and tucu-tucus showed more sites whose amino acid properties may be under positive selection in the cytochome b gene than their non-subterranean relatives, and ii) some of the sites identified to be under selection exclusively in subterranean taxa were shared among all subterranean taxa. The results given by these two approaches are consistent with each other and suggest a link between directional selection at the molecular level and niche shift.
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Papers by Federico Hoffmann