Presentation Title

Assessing the natural variation of the Hsp70 protein network in humans

Faculty Mentor

Nikolas Nikolaidis

Start Date

18-11-2017 10:00 AM

End Date

18-11-2017 11:00 AM

Location

BSC-Ursa Minor 49

Session

Poster 1

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

Understanding how genetic variation alters human evolution, adaptation, and disease predisposition is a fundamental goal in modern human genetics. Molecular chaperones as key orchestrators of cellular adaptation are critical for human health and disease. Therefore, it is of paramount importance to define how natural mutations alter the function of molecular chaperones and how these changes affect cell survival. In this study, we determined the natural variation and identified the modes of evolution of a major element of the human chaperone network, composed by Hsp70s, Hsp40s, and BAGs. Specifically, we collected single nucleotide polymorphisms (SNPs) from the 1000Genome project and analyzed these mutations using descriptive statistics and sequence evolution tools. The results can be summarized as follows: (I) the vast majority of the SNPs are rare having a frequency below 5% within humans. (II) Fifty percent of the genes had a significantly higher SNP density than the surrounding genes. (III) Eighty percent of the genes had significantly higher SNP density within their exonic regions as compared to both intronic and un-translated regions. (IV) The majority of genes contained higher proportion of synonymous-SNPs (sSNPs) than non-synonymous (nsSNPs) within known functional regions (domains). (V) Only 5% of the nsSNPs were predicted to be deleterious and have a functional outcome. (VI) Synonymous and non-synonymous distances showed the action of strong purifying selection, the intensity of which varied dramatically both between and within the gene families. Collectively, our results suggest that strong purifying selection due to functional constraints shaped their evolution in humans.

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Nov 18th, 10:00 AM Nov 18th, 11:00 AM

Assessing the natural variation of the Hsp70 protein network in humans

BSC-Ursa Minor 49

Understanding how genetic variation alters human evolution, adaptation, and disease predisposition is a fundamental goal in modern human genetics. Molecular chaperones as key orchestrators of cellular adaptation are critical for human health and disease. Therefore, it is of paramount importance to define how natural mutations alter the function of molecular chaperones and how these changes affect cell survival. In this study, we determined the natural variation and identified the modes of evolution of a major element of the human chaperone network, composed by Hsp70s, Hsp40s, and BAGs. Specifically, we collected single nucleotide polymorphisms (SNPs) from the 1000Genome project and analyzed these mutations using descriptive statistics and sequence evolution tools. The results can be summarized as follows: (I) the vast majority of the SNPs are rare having a frequency below 5% within humans. (II) Fifty percent of the genes had a significantly higher SNP density than the surrounding genes. (III) Eighty percent of the genes had significantly higher SNP density within their exonic regions as compared to both intronic and un-translated regions. (IV) The majority of genes contained higher proportion of synonymous-SNPs (sSNPs) than non-synonymous (nsSNPs) within known functional regions (domains). (V) Only 5% of the nsSNPs were predicted to be deleterious and have a functional outcome. (VI) Synonymous and non-synonymous distances showed the action of strong purifying selection, the intensity of which varied dramatically both between and within the gene families. Collectively, our results suggest that strong purifying selection due to functional constraints shaped their evolution in humans.