Family relationships among genes are important not just for their historical interest, but because they simplify the task of deciphering gene functions. Once the sequence of a newly discovered gene has been determined, a scientist can tap a few keys on a computer to search the entire database of known gene sequences for genes related to it. In many cases, the function of one or more of these homo-logs will have been already determined experimentally. Since gene sequence determines gene function, one can frequently make a good guess at the function of the new gene: it is likely to be similar to that of the already known homologs.
In this way, it is possible to decipher a great deal of the biology of an organism simply by analyzing the DNA sequence of its genome and using the information we already have about the functions of genes in other organisms that have been more intensively studied.
more Than 200 Gene Families Are common to All Three Primary Branches of the Tree of life
Given the complete genome sequences of representative organisms from all three domains—archaea, bacteria, and eukaryotes—we can search systematically for homologies that span this enormous evolutionary divide. In this way we can begin to take stock of the common inheritance of all living things. There are considerable difficulties in this enterprise. For example, individual species have often lost some of the ancestral genes; other genes have almost certainly been acquired by horizontal transfer from another species and therefore are not truly ancestral, even though shared. In fact, genome comparisons strongly suggest that both lineage-specific gene loss and horizontal gene transfer, in some cases between evolutionarily distant species, have been major factors of evolution, at least among prokaryotes. Finally, in the course of 2 or 3 billion years, some genes that were initially shared will have changed beyond recognition through mutation.
Because of all these vagaries of the evolutionary process, it seems that only a small proportion of ancestral gene families has been universally retained in a recognizable form. Thus, out of 4873 protein-coding gene families defined by comparing the genomes of 50 species of bacteria, 13 archaea, and 3 unicellular eukaryotes, only 63 are truly ubiquitous (that is, represented in all the genomes analyzed). The great majority of these universal families include components of the translation and transcription systems. This is not likely to be a realistic approximation of an ancestral gene set. A better—though still crude—idea of the latter can be obtained by tallying the gene families that have representatives in multiple, but not necessarily all, species from all three major domains. Such an analysis reveals 264 ancient conserved families. Each family can be assigned a function (at least in terms of general biochemical activity, but usually with more precision). As shown in Table 1–1, the largest number of shared gene families are involved in translation and in amino acid metabolism and transport. However, this set of highly conserved gene families represents only a very rough sketch of the common inheritance of all modern life. A more precise reconstruction of the gene complement of the last universal common ancestor will hopefully become feasible with further genome sequencing and more sophisticated forms of comparative analysis.
mutations Reveal the Functions of Genes
Without additional information, no amount of gazing at genome sequences will reveal the functions of genes. We may recognize that gene B is like gene A, but how do we discover the function of gene A in the first place? And even if we know the function of gene A, how do we test whether the function of gene B is truly the same as the sequence similarity suggests? How do we connect the world of abstract genetic information with the world of real living organisms?