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Comparative genomic analysis of the zebra finch degradome provides new insights into evolution of proteases in birds and mammals.

Quesada V, Velasco G, Puente XS, Warren WC, López-Otín C - BMC Genomics (2010)

Bottom Line: Furthermore, we found several zebra finch-specific features, such as duplications in CASP3 and BACE, and a large genomic expansion of acrosin.We have compared the degradomes of zebra finch, chicken and several mammalian species, with the finding of multiple differences which illustrate the evolution of the protease complement of these organisms.Detailed analysis of these changes in zebra finch proteases has shown that they are mainly related to immunological, developmental, reproductive and neural functions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006-Oviedo, Spain. clo@uniovi.es.

ABSTRACT

Background: The degradome -the complete repertoire of proteases in an organism- is involved in multiple key biological and pathological processes. Previous studies in several organisms have yielded sets of curated protease sequences which may be used to characterize the degradome in a novel genome by similarity. Differences between degradomes can then be related to physiological traits of the species under study. Therefore, the sequencing of the zebra finch genome allows the comparison between the degradomes of mammals and birds and may help to understand the biological peculiarities of the zebra finch.

Results: A set of curated protease sequences from humans and chicken was used to predict the sequences of 460 protease and protease-like genes in the zebra finch genome. This analysis revealed important differences in the evolution of mammalian and bird degradomes, including genomic expansions and deletions of caspases, cytotoxic proteases, kallikreins, matrix metalloproteases, and trypsin-like proteases. Furthermore, we found several zebra finch-specific features, such as duplications in CASP3 and BACE, and a large genomic expansion of acrosin.

Conclusions: We have compared the degradomes of zebra finch, chicken and several mammalian species, with the finding of multiple differences which illustrate the evolution of the protease complement of these organisms. Detailed analysis of these changes in zebra finch proteases has shown that they are mainly related to immunological, developmental, reproductive and neural functions.

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Phylogenetic relationship between zebra finch (zf_), chicken (gg_), and human (hs_) proteases in granzyme clusters. Numbers indicate the robustness of each node assessed by bootstrap. Azu1, azurocidin-1; df2, complement factor D; ela2, neutrophil elastase; prtn3, proteinase 3; gzm, granzyme; ela, elastase; cma1, chymase. Human azurocidin is included as an outgroup.
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Figure 2: Phylogenetic relationship between zebra finch (zf_), chicken (gg_), and human (hs_) proteases in granzyme clusters. Numbers indicate the robustness of each node assessed by bootstrap. Azu1, azurocidin-1; df2, complement factor D; ela2, neutrophil elastase; prtn3, proteinase 3; gzm, granzyme; ela, elastase; cma1, chymase. Human azurocidin is included as an outgroup.

Mentions: Immune cytotoxic proteases are serine proteases stored in the granules of neutrophils, mast cells, and natural killer lymphocytes and released upon activation. Once released, these proteases promote apoptosis of infected cells [15]. In humans, the genes encoding cytotoxic proteases are clustered in three genomic loci. The first cluster contains the genes encoding granzymes A (GZMA) and K (GZMK). As shown in Figure 2, GZMK is absent in the genomes of zebra finch and chicken, whereas GZMA is conserved in both birds. The second human cluster contains neutrophil elastase (ELA2), complement factor D (DF), azurocidin (AZU1), and proteinase 3 (PRTN3). This cluster seems to be lacking in both zebra finch and chicken (Figure 2). Finally, the third human cluster contains granzyme B (GZMB), granzyme H (GZMH), cathepsin G (CTSG), and chymase (CMA1). The genomes of both zebra finch and chicken contain a single protease gene related to all four human proteases, which we have named GZMZ. Notably, this protease has been duplicated in the zebra finch. The resulting novel zebra finch-specific granzyme (GZMZL) is classified as a non-peptidase homolog, lacking proteolytic capabilities, since its sequence features two substitutions at key catalytic residues. It should be noted that the most abundant granzymes in humans are A and B, which cause caspase-independent and caspase-dependent apoptosis, respectively. Therefore, this analysis predicts that avian granzyme A and granzyme Z may play complementary roles in the cytotoxic immune response. If expressed, granzyme Z-like might modulate the activity of granzyme Z by sequestering its substrates or inhibitors. Furthermore, it has been suggested that some of these granzymes absent in birds induce cell death by mitochondrial or autophagy-related pathways [16].


Comparative genomic analysis of the zebra finch degradome provides new insights into evolution of proteases in birds and mammals.

Quesada V, Velasco G, Puente XS, Warren WC, López-Otín C - BMC Genomics (2010)

Phylogenetic relationship between zebra finch (zf_), chicken (gg_), and human (hs_) proteases in granzyme clusters. Numbers indicate the robustness of each node assessed by bootstrap. Azu1, azurocidin-1; df2, complement factor D; ela2, neutrophil elastase; prtn3, proteinase 3; gzm, granzyme; ela, elastase; cma1, chymase. Human azurocidin is included as an outgroup.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2865498&req=5

Figure 2: Phylogenetic relationship between zebra finch (zf_), chicken (gg_), and human (hs_) proteases in granzyme clusters. Numbers indicate the robustness of each node assessed by bootstrap. Azu1, azurocidin-1; df2, complement factor D; ela2, neutrophil elastase; prtn3, proteinase 3; gzm, granzyme; ela, elastase; cma1, chymase. Human azurocidin is included as an outgroup.
Mentions: Immune cytotoxic proteases are serine proteases stored in the granules of neutrophils, mast cells, and natural killer lymphocytes and released upon activation. Once released, these proteases promote apoptosis of infected cells [15]. In humans, the genes encoding cytotoxic proteases are clustered in three genomic loci. The first cluster contains the genes encoding granzymes A (GZMA) and K (GZMK). As shown in Figure 2, GZMK is absent in the genomes of zebra finch and chicken, whereas GZMA is conserved in both birds. The second human cluster contains neutrophil elastase (ELA2), complement factor D (DF), azurocidin (AZU1), and proteinase 3 (PRTN3). This cluster seems to be lacking in both zebra finch and chicken (Figure 2). Finally, the third human cluster contains granzyme B (GZMB), granzyme H (GZMH), cathepsin G (CTSG), and chymase (CMA1). The genomes of both zebra finch and chicken contain a single protease gene related to all four human proteases, which we have named GZMZ. Notably, this protease has been duplicated in the zebra finch. The resulting novel zebra finch-specific granzyme (GZMZL) is classified as a non-peptidase homolog, lacking proteolytic capabilities, since its sequence features two substitutions at key catalytic residues. It should be noted that the most abundant granzymes in humans are A and B, which cause caspase-independent and caspase-dependent apoptosis, respectively. Therefore, this analysis predicts that avian granzyme A and granzyme Z may play complementary roles in the cytotoxic immune response. If expressed, granzyme Z-like might modulate the activity of granzyme Z by sequestering its substrates or inhibitors. Furthermore, it has been suggested that some of these granzymes absent in birds induce cell death by mitochondrial or autophagy-related pathways [16].

Bottom Line: Furthermore, we found several zebra finch-specific features, such as duplications in CASP3 and BACE, and a large genomic expansion of acrosin.We have compared the degradomes of zebra finch, chicken and several mammalian species, with the finding of multiple differences which illustrate the evolution of the protease complement of these organisms.Detailed analysis of these changes in zebra finch proteases has shown that they are mainly related to immunological, developmental, reproductive and neural functions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006-Oviedo, Spain. clo@uniovi.es.

ABSTRACT

Background: The degradome -the complete repertoire of proteases in an organism- is involved in multiple key biological and pathological processes. Previous studies in several organisms have yielded sets of curated protease sequences which may be used to characterize the degradome in a novel genome by similarity. Differences between degradomes can then be related to physiological traits of the species under study. Therefore, the sequencing of the zebra finch genome allows the comparison between the degradomes of mammals and birds and may help to understand the biological peculiarities of the zebra finch.

Results: A set of curated protease sequences from humans and chicken was used to predict the sequences of 460 protease and protease-like genes in the zebra finch genome. This analysis revealed important differences in the evolution of mammalian and bird degradomes, including genomic expansions and deletions of caspases, cytotoxic proteases, kallikreins, matrix metalloproteases, and trypsin-like proteases. Furthermore, we found several zebra finch-specific features, such as duplications in CASP3 and BACE, and a large genomic expansion of acrosin.

Conclusions: We have compared the degradomes of zebra finch, chicken and several mammalian species, with the finding of multiple differences which illustrate the evolution of the protease complement of these organisms. Detailed analysis of these changes in zebra finch proteases has shown that they are mainly related to immunological, developmental, reproductive and neural functions.

Show MeSH
Related in: MedlinePlus