Thursday, January 6, 2011

Comparative Genomics

Comparative genomics is an exciting new field of biological research in which the genome sequences of different species - human, mouse and a wide variety of other organisms from yeast to chimpanzees - are compared.

Comparative genomics is the analysis and comparison of genomes from different species. The purpose is to gain a better understanding of how species have evolved and to determine the function of genes and noncoding regions of the genome. Researchers have learned a great deal about the function of human genes by examining their counterparts in simpler model organisms such as the mouse. Genome researchers look at many different features when comparing genomes: sequence similarity, gene location, the length and number of coding regions (called exons) within genes, the amount of non-coding DNA in each genome and highly conserved regions maintained in organisms as simple as bacteria and as complex as humans.

Comparative genomics involves the use of computer programs that can line up multiple genomes and look for regions of similarity among them. Some of these sequence-similarity tools are accessible to the public over the Internet. One of the most widely used is BLAST, which is available from the National Center for Biotechnology Information (NCBI). BLAST is a set of programs designed to perform similarity searches on all available sequence data.

Comparative Genomics of Human and Mouse:

Mice and humans (indeed, most or all mammals including dogs, cats, rabbits, monkeys, and apes) have roughly the same number of nucleotides in their genomes - about 3 billion base pairs. This comparable DNA content implies that all mammals contain more or less the same number of genes.

The most significant differences between mice and humans are not in the number of genes each carries but in the structure of genes and the activities of their protein products. Gene for gene, we (Human being) are very similar to mice. What really matters is that subtle changes accumulated in each of the approximately 30,000 genes add together to make quite different organisms. The following phenomena make different two organisms different.
(1)  Genes and proteins interact in complex ways that multiply the functions of each.
(2)  A gene can produce more than one protein product through alternative splicing.
(3) Post-translational modifications events in each organism occur at different circumstances and these events
     do not always occur in an identical way in the two species
(4) A gene can produce more or less protein in different cells at various times in response to developmental or   
     environmental cues.
(5) Many proteins can express disparate functions in various biological contexts.

Thus, subtle distinctions are multiplied by the more than 30,000 estimated genes.

The often-quoted statement that we share over 98% of our genes with apes (chimpanzees, gorillas, and orangutans) actually should be put another way. That is, there is more than 95% to 98% similarity between related genes in humans and apes in general. (Just as in the mouse, quite a few genes probably are not common to humans and apes, and these may influence uniquely human or ape traits.) Similarities between mouse and human genes range from about 70% to 90%, with an average of 85% similarity but a lot of variation from gene to gene (e.g., some mouse and human gene products are almost identical, while others are nearly unrecognizable as close relatives). Some nucleotide changes are “neutral” and do not yield a significantly altered protein. Others, but probably only a relatively small percentage, would introduce changes that could substantially alter what the protein does.

Put these alterations in the context of known inherited human diseases: a single nucleotide change can lead to inheritance of sickle cell disease, cystic fibrosis, or breast cancer. A single nucleotide difference can alter protein function in such a way that it causes a terrible tissue malfunction. Single nucleotide changes have been linked to hereditary differences in height, brain development, facial structure, pigmentation, and many other striking morphological differences; due to single nucleotide changes, hands can develop structures that look like toes instead of fingers, and a mouse's tail can disappear completely. Single-nucleotide changes in the same genes but in different positions in the coding sequence might do nothing harmful at all. Evolutionary changes are the same as these sequence differences that are linked to person-to-person variation: many of the average 15% nucleotide changes that distinguish humans and mouse genes are neutral; some lead to subtle changes, whereas others are associated with dramatic differences. Add them all together, and they can make quite an impact, as evidenced by the huge range of metabolic, morphological, and behavioral differences we see among organisms.


Posted By:
Mitesh Jain.

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