Method and system for designing polynucleotide sequences and polynucleotide sequences obtained thereby

Abstract

Methods of designing a polynucleotide sequence for expressing a polypeptide-of-interest in a cell are provided. Also provided are artificial transcript sequences generated according to the present teachings. Further provided are methods of estimating the adaptiveness of a transcript sequence encoding a polypeptide-of-interest to a gene expression machinery in a cell.

What is claimed is: 
     
         1 . A method of estimating the adaptiveness of a transcript sequence encoding a polypeptide-of-interest (POI) to a gene expression machinery in a host cell, the method comprising:
 by a data processor, for each of a plurality of positions along the transcript sequence, generating a list of strings of genetic elements, each string being a subsequence of the transcript sequence, and is also a subsequence of at least one sequence of a reference set of polynucleotide sequences of said host cell;   by a data processor, processing each of at least a few of said lists to select a string of genetic elements based on a length of said string, thereby providing a processed list of strings of genetic elements; and   by a data processor, calculating at least one statistical measure for said processed list, wherein said at least one statistical measure is indicative of the adaptiveness of the transcript sequence to the gene expression machinery.   
     
     
         2 . The method according to  claim 1 , further comprising generating said reference set of polynucleotide sequences. 
     
     
         3 . The method according to  claim 1 , wherein said selected string is a longest string in said list. 
     
     
         4 . The method according to  claim 1 , wherein said statistical measure is based on a sum of lengths of said selected strings in said processed list. 
     
     
         5 . The method according to  claim 1 , wherein said length is calculated in terms of an entity selected from the group consisting of amino acids, codons and nucleotides. 
     
     
         6 . The method of  claim 1 , wherein said genetic elements are codon fragments. 
     
     
         7 . The method of  claim 1 , wherein at least one of said strings comprise a coding sequence. 
     
     
         8 . The method of  claim 1 , wherein at least one of said strings comprise a non-coding sequence. 
     
     
         9 . The method of  claim 1 , wherein said genetic elements are codon pairs. 
     
     
         10 . The method of  claim 1 , wherein said genetic elements are nucleotides. 
     
     
         11 . The method of  claim 1 , wherein said reference set of polynucleotide sequences is selected from the group consisting of genomic DNA, RNA and ESTs. 
     
     
         12 . The method of  claim 1 , wherein said the reference set comprises an entire genome of the host cell. 
     
     
         13 . A method of estimating the adaptiveness of a transcript sequence encoding a polypeptide-of-interest (POI) to a gene expression machinery in a cell, wherein the transcript sequence is endogenous to the cell, the method comprising:
 by a data processor, for each of a plurality of positions along the transcript sequence, generating a list of strings of genetic elements, each string being a subsequence of the transcript sequence, and is also a subsequence of at least one sequence of a reference set of polynucleotide sequences of said host cell;   by a data processor, processing each of at least a few of said lists to select a string of genetic elements based on a length of said string, thereby providing a processed list of strings of genetic elements; and   by a data processor, calculating at least one statistical measure for said processed list, wherein said at least one statistical measure is indicative of the adaptiveness of the transcript sequence to the gene expression machinery.   
     
     
         14 . The method according to  claim 1 , further comprising generating said reference set of polynucleotide sequences. 
     
     
         15 . The method of  claim 1 , wherein said the reference set comprises an entire genome of the host cell. 
     
     
         16 . The method according to  claim 1 , wherein said selected string is a longest string in said list. 
     
     
         17 . An artificial transcript having a nucleic acid sequence encoding a polypeptide-of-interest (POI) designed for expression in a host cell, said host cell being characterized by a reference set of polynucleotide sequences, said artificial transcript comprising at least one string of genetic elements being at least 4 nucleotides in length, said at least one string being embedded in said nucleic acid sequence to as to encode the POI, said at least one string being represented in said reference set of polynucleotide sequences, and wherein said at least one string and said nucleic acid sequence are heterologous and with the proviso that when said at least one string is a single string of genetic elements, said single string is not located at a 5′ terminus of said nucleic acid sequence. 
     
     
         18 . The artificial transcript of  claim 17 , wherein said host cell is heterologous to the POI. 
     
     
         19 . The artificial transcript of  claim 17 , wherein said host cell endogenously expresses the POI. 
     
     
         20 . An expression construct comprising the polynucleotide expressing the artificial transcript of  claim 17  and a promoter suitable for expressing said artificial transcript in said host cell.