Question

two methods of gene annotation: ab initio and homology-based.

1) Generally describe how each method (ab initio and homology-base gene annotation) identifies a gene (i.e. what does each look for?).

2) Based on the differences between these methods, give one example of a type of gene that would be detected by one method but not the other and explain your answer

Answer 1

Ans1 ) Protein coding genes is habitually grounded on transcriptome sequencing data ab-initio and homology based prediction. recently, it was proved that intron position conservation improves homology baqsed gene prediction, and that experimental data improves ab-initio gene prediction

Ab-initio Method:-

Once the primary sequence of a genome was accomplished, the simplest andcost- effective method is to carry out a genome-wide ab initio gene finding toannotate a whole set of exon-intron structures and infer all the possibly encoded proteins . Such programs in fact do not entail experimental evidences of a priorknowledge of a specific genomic portion. They go through an uncharacterised DNA sequence searching for signals (such as start andstop codons, splice sites, polyadenylation sites, branchpoints) and features of coding regions, subsequentely used to accumulate a finl gene structure. Many programs such as GENSCAN, Gene-Mark, or GeneID distinguish coding from non-coding regions of eukrayotic genomes by means of an substitute coding measure based on hexanucleotide usage

Homology Based Method:-

In distinction with ab initio approaches, gene prediction systems based on external evidences intended to recognize gene structures using similarity search results and expression data(ESTs, cDNAs, and proteins). Usually, approaches relying on evidence make practice of a statistically substantial homology between an unknown genomic sequence and a protein or DNA sequence existing in a databse in order to regulate transcribed and/or coding regions. Presentely, the bezst approaches to distinguish similarities between sequences are based on local alignment method either optimal such as Smith- Waterman algorithm or heuristic as implemented in BLAST,FASTA, and BLAT programs.

Ans 2 ) Example:- Suppose we take a gene of Drosopjhila melanogaster and its F gene (Human gene predictor) was selected that have organ specific parameters for humans. For identification of potential protein- coding regions in Adh region of Drosophila sequence and used three prediction programs(F genes, Fgenesh and Fgenesh+).Fgenesh is a HMM based algorithm whose gene was annotated in gene bank. These selected genes were then annotated by ab-initio method which were based on discrimination trained to predict human genes.

It could not used homology based method here because here ESTs were too less to be predicted thats why ab initio was used as it is derived from  external sequence or sequences already present.