Several editors (Graveley, Ule, Henikoff, Doolittle) said that the discovery of "genes in pieces" was a very significant advance in genome biology in the past sixty years. You can't argue with that.
George Weinstock counts restriction mapping as a key advance. I understand his point since the development of restriction mapping gave us maps of the actual structure of the genome for the first time (genetic maps are imprecise and depend on the presence of mutations).
A new regulatory paradigm: micoRNA
John Rinn, who coincidentally works on small RNAs thinks this is a significant advance in genomics. I don't agree.
The original 'data explosion': microarrays
Alicia Oshlack is an astrophysicist who got into genomics through bioinformatics and the analysis of microarray data. Microarrays are important in genomics and should be included in any list of significant advances as long as the list includes technological advances.
Unlocking 'genetic messages': sequencing technologies
Michael Schatz says, "The most significant advance in genome biology since 25 April 1953 has been the rise of large-scale DNA sequencing ...." He is correct, if technologies are to be included in the list.
'Sequence is power': the human and mouse genome projects
Chris Ponting, Mark Gerstein, and Peter Fraser think that the publication of the human genome sequence is the most significant advance in genome biology. I suppose it depends on what you want to know about genomes. If your focus is on humans and medicine then, obviously, the sequence of the human genome is important. I thought the sequences of the yeast, nematode, and Drosophila genomes were pretty exciting and so were the sequences of bacterial genomes.
Retelling the human story: analysis of ancient and historical DNA
The is Detlef Weigel's contribution.
The exception to the rule: lateral gene transfer
Curtis Huttenhower thinks that the discovery of lateral gene transfer is "one of the most remarkable [discoveries] in the history of genome biology."
Nobody mentioned junk DNA and the resolution of the C-value paradox. Nobody mentioned the small number of genes in the human genome in spite of the fact that a great many articles begin with the claim that this was a shocking discovery [but see False History and the Number of Genes]. Jernej Ule mentioned alternative splicing but nobody else did in spite of the fact that many papers claim that most human genes are capable of making several different proteins. This is also a false claim, IMHO, but you'd never know that from reading the journal. Peter Fraser was the only one who mentioned the vast regulatory network of enhancers as claimed by the ENCODE Consortium. If true, that would clearly count as a major discovery. (It's not true.) Eukaryotic genomes are chock full of defective transposons but none of the editors thought that was a key advance in our understanding of the genome.
Doolittle, W.F., Fraser, P., Gerstein, M.B., Graveley, B.R., Henikoff, S., Huttenhower, C., Oshlack, A., Ponting, C.P., Rinn, J.L., Schatz, M., Ule, J., Weigel, D., and Weinstock, G.M. (2013) Sixty years of genome biology. Genome Biol, 14(4), 113. [doi: 10.1186/gb-2013-14-4-113]