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Evolutionary history of tissue kallikreins.

Pavlopoulou A, Pampalakis G, Michalopoulos I, Sotiropoulou G - PLoS ONE (2010)

Bottom Line: The chromosomal co-localization in a single cluster distinguishes KLKs from trypsin and other trypsin-like proteases which are spread in different genetic loci.All the defining features of the KLKs were further found to be conserved in the novel KLK protein sequences.The study of this unique family will further assist in selecting new model organisms for functional studies of proteolytic pathways involving KLKs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, School of Health Sciences, University of Patras, Rion-Patras, Greece.

ABSTRACT
The gene family of human kallikrein-related peptidases (KLKs) encodes proteins with diverse and pleiotropic functions in normal physiology as well as in disease states. Currently, the most widely known KLK is KLK3 or prostate-specific antigen (PSA) that has applications in clinical diagnosis and monitoring of prostate cancer. The KLK gene family encompasses the largest contiguous cluster of serine proteases in humans which is not interrupted by non-KLK genes. This exceptional and unique characteristic of KLKs makes them ideal for evolutionary studies aiming to infer the direction and timing of gene duplication events. Previous studies on the evolution of KLKs were restricted to mammals and the emergence of KLKs was suggested about 150 million years ago (mya). In order to elucidate the evolutionary history of KLKs, we performed comprehensive phylogenetic analyses of KLK homologous proteins in multiple genomes including those that have been completed recently. Interestingly, we were able to identify novel reptilian, avian and amphibian KLK members which allowed us to trace the emergence of KLKs 330 mya. We suggest that a series of duplication and mutation events gave rise to the KLK gene family. The prominent feature of the KLK family is that it consists of tandemly and uninterruptedly arrayed genes in all species under investigation. The chromosomal co-localization in a single cluster distinguishes KLKs from trypsin and other trypsin-like proteases which are spread in different genetic loci. All the defining features of the KLKs were further found to be conserved in the novel KLK protein sequences. The study of this unique family will further assist in selecting new model organisms for functional studies of proteolytic pathways involving KLKs.

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Evolution of KLKs.Schematic representation of key events occurring through the evolutionary history of KLKs.
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pone-0013781-g006: Evolution of KLKs.Schematic representation of key events occurring through the evolutionary history of KLKs.

Mentions: The reconstructed phylogenetic tree in Figure S2 also demonstrates that the two piscine peptide sequences previously described as KLK-related [44] are totally unrelated to KLKs. Instead these proteins cluster with the known complement factor D/adipsin proteins [45], [46] (Figure S2). Finally, Figure 6 summarizes the evolution events in the KLK gene family.


Evolutionary history of tissue kallikreins.

Pavlopoulou A, Pampalakis G, Michalopoulos I, Sotiropoulou G - PLoS ONE (2010)

Evolution of KLKs.Schematic representation of key events occurring through the evolutionary history of KLKs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2967472&req=5

pone-0013781-g006: Evolution of KLKs.Schematic representation of key events occurring through the evolutionary history of KLKs.
Mentions: The reconstructed phylogenetic tree in Figure S2 also demonstrates that the two piscine peptide sequences previously described as KLK-related [44] are totally unrelated to KLKs. Instead these proteins cluster with the known complement factor D/adipsin proteins [45], [46] (Figure S2). Finally, Figure 6 summarizes the evolution events in the KLK gene family.

Bottom Line: The chromosomal co-localization in a single cluster distinguishes KLKs from trypsin and other trypsin-like proteases which are spread in different genetic loci.All the defining features of the KLKs were further found to be conserved in the novel KLK protein sequences.The study of this unique family will further assist in selecting new model organisms for functional studies of proteolytic pathways involving KLKs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, School of Health Sciences, University of Patras, Rion-Patras, Greece.

ABSTRACT
The gene family of human kallikrein-related peptidases (KLKs) encodes proteins with diverse and pleiotropic functions in normal physiology as well as in disease states. Currently, the most widely known KLK is KLK3 or prostate-specific antigen (PSA) that has applications in clinical diagnosis and monitoring of prostate cancer. The KLK gene family encompasses the largest contiguous cluster of serine proteases in humans which is not interrupted by non-KLK genes. This exceptional and unique characteristic of KLKs makes them ideal for evolutionary studies aiming to infer the direction and timing of gene duplication events. Previous studies on the evolution of KLKs were restricted to mammals and the emergence of KLKs was suggested about 150 million years ago (mya). In order to elucidate the evolutionary history of KLKs, we performed comprehensive phylogenetic analyses of KLK homologous proteins in multiple genomes including those that have been completed recently. Interestingly, we were able to identify novel reptilian, avian and amphibian KLK members which allowed us to trace the emergence of KLKs 330 mya. We suggest that a series of duplication and mutation events gave rise to the KLK gene family. The prominent feature of the KLK family is that it consists of tandemly and uninterruptedly arrayed genes in all species under investigation. The chromosomal co-localization in a single cluster distinguishes KLKs from trypsin and other trypsin-like proteases which are spread in different genetic loci. All the defining features of the KLKs were further found to be conserved in the novel KLK protein sequences. The study of this unique family will further assist in selecting new model organisms for functional studies of proteolytic pathways involving KLKs.

Show MeSH
Related in: MedlinePlus