Natural selection on MRNA secondary structure and its correlation with protein functional groups

Natural selection may occur at multiple levels of the biological hierarchy, including at the molecular level. It may occur on any phenotypic trait that evidences variation and that is heritable. This research uses computational methods to investigate whether the stability of the secondary structures of mRNAs has been the subject of natural selection. The DNA sequence that codes for a particular target protein is only partially determined by that protein, since the redundancy of the genetic code permits multiple possible synonymous codons for each peptide. An RNA transcript of a DNA protein template (gene) folds back on itself through complementary base pairing, resulting in an mRNA secondary structure. This mRNA secondary structure tends to have a configuration that minimizes free energy. Two synonymous mRNAs, coding for the identical protein with different sets of synonymous codons, will in general fold into different secondary structures with different minimum free energies (MFEs). The secondary structure of an mRNA is therefore a phenotypic trait that could be a target of natural selection. Several related questions were investigated: 1) Is there natural selection on the stability of RNA secondary structure, across various types of organisms? 2) Does the MFE of microbial mRNAs correlate with the function of the target protein? 3) Is there evidence of natural selection on the nucleotide composition and/or secondary structure of the prefixes and suffixes of bacterial mRNAs? 4) Is there natural selection on the secondary structures and substructures of subviral RNAs? These questions were investigated using large-scale simulations, based on the generation of sets of randomized synthetic mRNAs for particular genes. The secondary structure of each mRNA (naturally occuring and synthetic) was then computationally predicted. The experiments were performed on the complete sets of genes of a number of prokaryotes and eukaryotes. Two types of randomized experiments were performed on each genetic data set, providing an independent confirmation of the results. In the first method of randomization, synonymous mRNAs were generated for each gene, creating sequences that code for the identical protein, with a frequency of codon use characteristic of the organism. In the second method of randomization, the nucleotides of the mRNA were permuted in manner that does not preserve the mRNA sequence\u27s target protein, but exactly preserves the mRNA sequence\u27s nucleotide and dinucleotide frequencies. The MFE of each naturally occuring mRNA sequence is then compared with the MFEs of the corresponding randomized sequences. A pattern of deviation, across an entire organism, of the value of the MFE of the naturally occurring sequence from that of the corresponding randomized sequences is evidence of natural selection on the stability of the mRNA transcript. This research establishes that: In all prokaryotes studied, natural selection has favored of highly stable (lower MFE) mRNAs. In some prokaryotes, natural selection has also favored highly unstable mRNAs. No statistically significant evidence of such selection was found in eukaryotes. The distributions of MFEs of mRNAs of 25 broad functional classes of proteins (COGs - Clusters of Orthologous Groups) of five microbes and yeast correlate to functional class. mRNA prefixes have a distinctive MFE signature. The naturally occurring prefixes display more structure, on average, than randomized sequences with identical nucleotide and dinucleotide content, suggesting that natural selection favors secondary structure in the prefix of mRNA. Viroids (with RNA genomes) have highly stable secondary structures and the structures are similar among the viroids belonging to the same family. The results indicate that natural selection on the MFE of mRNA is widespread in the evolution of the genome

Συνεισφορά ρετρομεταθετών και επαναλαμβανόμενων στοιχείων στη μοριακή οργάνωση των χρωμοσωμάτων του Bactrocera oleae

Ο δάκος της ελιάς, Bactrocera oleae, είναι το πιο επιβλαβές έντομο των ελαιοκαλλιεργειών. Λόγω της εξαιρετικής οικονομικής σημασίας του πρέπει να αναπτυχθούν μέθοδοι δακοπροστασίας, αποτελεσματικές από αυτές που εφαρμόζονται στις μέχρι σήμερα. Η περιορισμένη γνώση της μοριακής οργάνωσης του εντόμου αποτελεί εμπόδιο για την εύρεση γενετικών μεθόδων διαχείρισης. Σκοπός της παρούσας εργασίας ήταν η συνεισφορά στην απόκτηση γνώσης της μοριακής οργάνωσης. Στα πλαίσια του στόχου αυτού επιτεύχθηκε η χαρτογράφηση και επεξεργασία του φάγου 276 που οδήγησε στην απομόνωση μιας επαναλαμβανόμενης αλληλουχίας 300bp, που ονομάστηκε BoR300. To BoR 300 απουσιάζει από γνωστά έντομα της τάξης των διπτέρων όπως το Ceratitis Capitata, η Drosophila melanogasler και το Anopheles gambieae αλλά και από είδη του γένους Bactrocera όπως το Β. correctα,το Β. currenbitae και το Β. Dorsalis. To BoR300 είναι ένα επαναλαμβανόμενο στοιχείο που εντοπίζεται ειδικά στο Bactrocera oleae

Sulla distanza di mutazione tra sequenze biologiche

BpMatch è un nuovo algoritmo la cui funzione è di calcolare efficientemente, date le sequenze S e T, la massima copertura di T utilizzando solo sottosequenze e sottosequenze invertite complementate di S, di lunghezza minima l, eventualmente sovrapposte, e, nella copertura massima, di minimizzare il numero di sottosequenze utilizzate. Il problema viene risolto eseguendo una preelaborazione di S (indipendentemente dalla sequenza di cui successivamente verrà poi cercata la massima copertura e, quindi, preelaborazione da effettuare una sola volta e valida per ogni T), generando un grafo che permetta un rapido riconoscimento delle sottosequenze di S. I grafi G e G' devono essere generati rispettivamente dalla sequenza S e da S invertita e complementata, poi, utilizzando G, G' e T, il calcolo della copertura massima può essere computato in tempo O(u*log(log(n))) (n=|S| e u=|T|) nel caso medio ed in spazio lineare