Building Biological Complexity with Limited Genes

Abstract

How organismal complexity is achieved is a fundamental biological issue. The surprising revelation that complex eukaryotes have fewer than expected genes presents an important challenge for deciphering how organisms achieve complexity. The genome size and the gene number do not necessarily correlate in a consistent manner with the perceived organismal complexity. In this review, we focus on known molecular mechanisms that increase genetic complexity at the molecular and functional levels, and discuss features that have likely contributed to organismal complexity.

Multiple pattern matching: a Markov chain approach

“…In addition to modular patterns that contain correlations through base pairing, modular patterns that do not (as far as is currently known) require base pairing are also important for processes involving RNA. For example, transcriptional regulation requires combinatorial regulation of binding sites for transcription factors that activate and repress genes; splicing regulation requires specific combinations of splicing enhancers and repression; and microRNA targeting appears to be combinatorial [SRK06]. Many existing software packages for detecting overrepresented words, such as the MobyDick package [BLS00], identify words that are surprisingly common given the partition function by which they could be comprised of shorter words, but fail to take into account correlations between word abundances that could be caused by partial overlap of words of the same length.…”

“…However, recent work has developed other pattern-matching problems related to RNA sequences. For example, multiple short protein-or RNA-binding sequence motifs can combine to regulate a range of biological processes, including splicing and polyadenylation [SRK06]. Similarly, 6-base seed sequences that bind short microRNA molecules (miRNAs) appear to work in concert to repress translation [LBB05].…”

Genome-Wide Identification of Alternatively Spliced mRNA Targets of Specific RNA-Binding Proteins

“…For example, the Drosophila homolog of the human Down Syndrome Cell Adhesion Molecule (DSCAM) gene potentially encodes three times as many alternatively spliced transcripts (∼38,000) as the total number of predicted genes (∼13,600) in the fruitfly [3], [4]. Thus, alternative splicing, among several processes [5], provides a mechanism to generate enormous molecular diversity from a single gene, and provides a rich source of functional diversity in multi-cellular eukaryotes [6], [7]. Alternative splicing plays an important role in numerous cellular and developmental processes such as cell growth and differentiation, cell signaling, programmed cell death, and nonsense-mediated decay [8], [9].…”