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Molecular evolution of GYPC: evidence for recent structural innovation and positive selection in humans.

ABSTRACT: GYPC encodes two erythrocyte surface sialoglycoproteins in humans, glycophorin C and glycophorin D (GPC and GPD), via initiation of translation at two start codons on a single transcript. The malaria-causing parasite Plasmodium falciparum uses GPC as a means of invasion into the human red blood cell. Here, we examine the molecular evolution of GYPC among the Hominoidea (Greater and Lesser Apes) and also the pattern of polymorphism at the locus in a global human sample. We find an excess of nonsynonymous divergence among species that appears to be caused solely by accelerated evolution of GYPC in the human lineage. Moreover, we find that the ability of GYPC to encode both GPC and GPD is a uniquely human trait, caused by the evolution of the GPC start codon in the human lineage. The pattern of polymorphism among humans is consistent with a hitchhiking event at the locus, suggesting that positive natural selection affected GYPC in the relatively recent past. Because GPC is exploited by P. falciparum for invasion of the red blood cell, we hypothesize that selection for evasion of P. falciparum has caused accelerated evolution of GYPC in humans (relative to other primates) and that this positive selection has continued to act in the recent evolution of our species. These data suggest that malaria has played a powerful role in shaping molecules on the surface of the human red blood cell. In addition, our examination of GYPC reveals a novel mechanism of protein evolution: co-option of untranslated region (UTR) sequence following the formation of a new start codon. In the case of human GYPC, the ancestral protein (GPD) continues to be produced through leaky translation. Because leaky translation is a widespread phenomenon among genes and organisms, we suggest that co-option of UTR sequence may be an important source of protein innovation.

SUBMITTER: Wilder JA

PROVIDER: S-EPMC2775107 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Molecular evolution of GYPC: evidence for recent structural innovation and positive selection in humans.

Wilder Jason A JA Hewett Elizabeth K EK Gansner Meredith E ME

Molecular biology and evolution 20090813 12

GYPC encodes two erythrocyte surface sialoglycoproteins in humans, glycophorin C and glycophorin D (GPC and GPD), via initiation of translation at two start codons on a single transcript. The malaria-causing parasite Plasmodium falciparum uses GPC as a means of invasion into the human red blood cell. Here, we examine the molecular evolution of GYPC among the Hominoidea (Greater and Lesser Apes) and also the pattern of polymorphism at the locus in a global human sample. We find an excess of nonsy ...[more]

PMID: 19679754

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Project description:Hosts and viruses are locked in an evolutionary arms race. Hosts are constantly evolving to suppress virulence and replication, while viruses, which are reliant on host machinery for survival and reproduction, develop counterstrategies to escape this immune defense. Viruses must also adapt to novel conditions while establishing themselves in a host species. Both processes provide strong selection for viral adaptation. Understanding adaptive evolution in insect viruses can help us to better understand adaptive evolution in general and is important due to the use of these viruses as biocontrol agents and for protecting ecologically or economically important species from outbreaks. Here we examine the molecular evolution of baculoviruses and nudiviruses, a group of insect-infecting viruses with key roles in biocontrol. We looked for signatures of selection between genomes of baculoviruses infecting a range of species and within a population of baculoviruses. Both analyses found only a few strong signatures of positive selection, primarily in replication- and transcription-associated genes and several structural protein genes. In both analyses, we detected a conserved complex of genes, including the helicase gene, showing consistently high levels of adaptive evolution, suggesting that they may be key in antagonistic coevolution to escape host suppression. These genes are integral to the baculovirus life cycle and may be good focal genes for developing baculoviruses as effective biocontrol agents or for targeting baculoviruses infecting ecologically relevant species. Recombination and complex genomes make evolution in these double-stranded DNA viruses more efficient than that in smaller RNA viruses with error-prone replication, as seen via signatures of selection in specific genes within a population of baculoviruses.IMPORTANCE Most viral evolutionary studies focus on RNA viruses. While these viruses cause many human and animal diseases, such studies leave us with a lesser understanding of how DNA viruses adapt to hosts and how the host responds to these pathogens. In this paper, we focus on the evolution of baculoviruses, a group of insect-infecting DNA viruses, many of which have been used in biocontrol. We find that most of the genome is under purifying selection, with only a few key genes evolving adaptively. Our results provide a glimpse into how DNA viruses differ from RNA viruses in their evolutionary dynamics and identify genes that are key to DNA virus adaptation, improving our understanding of how this group of pathogens evolves.

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Molecular evolution of GYPC: evidence for recent structural innovation and positive selection in humans.

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Molecular evolution of GYPC: evidence for recent structural innovation and positive selection in humans.

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