A “Game” Introduction to Bioinformatic Sequence Comparisons (2007)

Genome Sequencing, Bioinformatics & The Unity Of Biology Genome sequencing projects have produced a deluge of information regarding the entire genetic complement of numerous biological organisms. Interpreting and understanding this information stands as one of the greatest challenges facing us and has helped lead to the emergence of a new discipline termed bioinformatics (Bloom, 2001). Today, scientists decipher sequence data using a variety of tools to identify and characterize genes encoding discrete products such as polypeptides that perform a myriad of cellular functions. Many of these tools are readily accessible as Web applications for incorporation into classroom activities, yet the bases for these tools can be often overlooked. Here, a card game is described as an appropriate avenue for introduction to bioinformatic sequence comparisons and their underlying principles. This card game provides students with an opportunity to learn about relationships regarding amino acid structure and chemistry and, more importantly, understand scoring mechanisms derived from substitution patterns in polypeptides that allow scientists to determine similarity between amino acid sequences and make predictions about enzyme structure and function. One prominent and interesting perspective generated by genome sequencing and the subsequent bioinformatic analysis of this data has been the observed similarity between all organisms at the DNA and amino acid sequence level. Genome sequencing provides clear evidence that differences between organisms are less the nature of the genes present, but more a result of regulated gene expression and how gene products are utilized within cell physiology. Interestingly, this perspective was offered by Dr. Francois Jacob (1977) in his landmark paper Evolution and Tinkering almost 30 years ago. However, as Dr. Eric Lander, a leader in genomics, has recently stated: I think it was something of a surprise to see how unified life was. In the middle of the 20th century maybe people imagined that every branch of life had completely different mechanisms and to find that in fact, all branches of life (certainly all branches of nucleated cells) use the same basic mechanism... Of course in retrospect, it's perfectly obvious. I mean life isn't going to go to the trouble of reinventing things. Instead, it reuses things. It slightly modifies them. But I bet if you had gone around and taken a survey back in the 1960s or 1970s and said, You're going to find the same basic genes controlling a soil nematode and a fruit fly and a human in terms of their development or You are going to find the same basic genes controlling cancer and a baker's yeast. I bet most people wouldn't have voted yes. Lander, 2004 Today, this evolutionary theme is implicit in our interpretation of genome sequence data using sequence comparisons and evident in various recent texts highlighting the unity of biology as revealed through molecular and genome sequence data (Carroll, 2005; Carroll et al., 2004; Ptashne & Gann, 2001). What Insight Is Gained from Sequence Comparisons? Due to the degeneracy of the genetic code, sequence identity or similarity between two or more sequences can be difficult to discover at the DNA sequence level. As a result, one of the most powerful approaches for gaining insight into genome sequences is based simply on amino acid sequence comparisons between new, uncharacterized amino acid sequences predicted from genome DNA sequences, and amino acid sequences of known function. The rationale for these comparisons is simply the more similar any two particular amino acid sequences are, the more likely they have the same structure and/or function. Clearly, this assumption is not always accurate, but it provides a good starting point for gaining structural or functional insight on molecules from sequence information. …